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Abstract Objectives This study developed a deep learning radiomics (DLR) model utilizing baseline computed tomography enterography (CTE) to non-invasively predict stratified healing in Crohn’s disease (CD) patients following infliximab (IFX) treatment. Methods The study included 246 CD patients diagnosed at three hospitals. From the first two hospitals, 202 patients were randomly divided into a training cohort (n = 141) and a testing cohort (n = 61) in a 7:3 ratio. The remaining 44 patients from the third hospital served as the validation cohort. Radiomics and deep learning features were extracted from both the active lesion wall and mesenteric adipose tissue. The most valuable features were selected using univariate analysis and least absolute shrinkage and selection operator (LASSO) regression. Multivariate logistic regression was then employed to construct the radiomics, deep learning, and DLR models. Model performance was evaluated using receiver operating characteristic (ROC) curves. Results The DLR model achieved an area under the ROC curve (AUC) of 0.948 (95% CI: 0.916–0.980), 0.889 (95% CI: 0.803–0.975), and 0.938 (95% CI: 0.868–1.000) in the training, testing, and validation cohorts, respectively in predicting mucosal healing (MH). Furthermore, the diagnostic performance of DLR model in predicting transmural healing (TH) was 0.856 (95% CI: 0.776–0.935). Conclusions We have developed a DLR model based on the radiomics and deep learning features of baseline CTE to predict stratified healing (MH and TH) in CD patients following IFX treatment with high accuracies in both testing and external cohorts. Critical relevance statement The deep learning radiomics model developed in our study, along with the nomogram, can intuitively, accurately, and non-invasively predict stratified healing at baseline CT enterography. Key Points Early prediction of mucosal and transmural healing in Crohn’s Disease patients is beneficial for treatment planning. This model demonstrated excellent performance in predicting mucosal healing and had a diagnostic performance in predicting transmural healing of 0.856. CT enterography images of active lesion walls and mesenteric adipose tissue exhibit an association with stratified healing in Crohn’s disease patients. Graphical Abstract

Abstract Intercellular cell adhesion molecule-1 (ICAM-1) is frequently overexpressed in non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the mechanism underlying the negative effects of neoplastic ICAM-1 remains obscure. Herein, we demonstrate that the survival of NSCLC cells but not normal human bronchial epithelial cells requires an anti-apoptosis signal triggered by fibrinogen γ chain (FGG)–ICAM-1 interaction. ICAM-1–FGG ligation preserves the tyrosine phosphorylation of ICAM-1 cytoplasmic domain and its association with SHP-2, and subsequently promotes Akt and ERK1/2 activation but suppresses JNK and p38 activation. Abolishing ICAM-1–FGG interaction induces NSCLC cell death by activating caspase-9/3 and significantly inhibits tumor development in a mouse xenograft model. Finally, we developed a monoclonal antibody against ICAM-1–FGG binding motif, which blocks ICAM-1‒FGG interaction and effectively suppresses NSCLC cell survival in vitro and tumor growth in vivo. Thus, suppressing ICAM-1–FGG axis provides a potential strategy for NSCLC targeted therapy.

Abstract One question in lymphocyte homing is how integrins are rapidly activated to enable immediate arrest of fast rolling lymphocytes upon encountering chemokines at target vascular beds given the slow chemokine-induced integrin inside-out activation. Herein we demonstrate that chemokine CCL25-triggered Ca2+ influx induces T cell membrane-proximal external Ca2+ concentration ([Ca2+]ex) drop in 6 s from physiological concentration 1.2 mM to 0.3 mM, a critical extracellular Ca2+ threshold for inducing αLβ2 activation, triggering rapid αLβ2 activation and T cell arrest before occurrence of αLβ2 inside-out activation. Talin knockdown inhibits the slow inside-out activation of αLβ2 but not [Ca2+]ex drop-triggered αLβ2 quick activation. Blocking Ca2+ influx significantly suppresses T cell rolling-to-arrest transition and homing to skin lesions in a mouse psoriasis model, thus alleviating skin inflammation. [Ca2+]ex decrease-triggered rapid integrin activation bridges the gap between initial chemokine stimulation and slow integrin inside-out activation, ensuring immediate lymphocyte arrest and subsequent diapedesis on the right location.

Abstract Background Soybean cyst nematodes (SCN) as animal parasites of plants are not usually interested in killing the host but are rather focused on completing their life cycle to increase population, resulting in substantial yield losses. Remarkably, some agricultural soils after long-term crop monoculture show a significant decline in SCN densities and suppress disease in a sustainable and viable manner. However, relatively little is known about the microbes and mechanisms operating against SCN in such disease-suppressive soils. Results Greenhouse experiments showed that suppressive soils (S) collected from two provinces of China and transplantation soils (CS, created by mixing 10% S with 90% conducive soils) suppressed SCN. However, SCN suppressiveness was partially lost or completely abolished when S soils were treated with heat (80 °C) and formalin. Bacterial community analysis revealed that the specific suppression in S and CS was mainly associated with the bacterial phylum Bacteroidetes, specifically due to the enrichment of Chitinophaga spp. and Dyadobacter sp., in the cysts. SCN cysts colonized by Chitinophaga spp. showed dramatically reduced egg hatching, with unrecognizable internal body organization of juveniles inside the eggshell due to chitinase activity. Whereas, Dyadobacter sp. cells attached to the surface coat of J2s increased soybean resistance against SCN by triggering the expression of defence-associated genes. The disease-suppressive potential of these bacteria was validated by inoculating them into conducive soil. The Dyadobacter strain alone or in combination with Chitinophaga strains significantly decreased egg densities after one growing cycle of soybeans. In contrast, Chitinophaga strains alone required more than one growing cycle to significantly reduce SCN egg hatching and population density. Conclusion This study revealed how soybean monoculture for decades induced microbiota homeostasis, leading to the formation of SCN-suppressive soil. The high relative abundance of antagonistic bacteria in the cyst suppressed the SCN population both directly and indirectly. Because uncontrolled proliferation will likely lead to quick demise due to host population collapse, obligate parasites like SCN may have evolved to modulate virulence/proliferation to balance these conflicting needs. Video Abstract

Introduction: The combination of photothermal therapy and chemotherapy has emerged as a promising strategy for cancer treatment. The green synthesis of gold nanoparticles (Au NPs) using extracts from traditional Chinese medicine Scutellaria barbata D. Don (Scu) has revealed an economical, sustainable, and eco-friendly approach for the outstanding anticancer activities. Methods: Scu extract was mixed with HAuCl4 solution to fabricate Scu-Au NPs. The synthesis process was optimized by varying the reaction temperature, reaction time, and HAuCl4 concentration. The changes in the components of Scu before and after synthesis were analyzed using the 3,5-dinitrosalicylic acid (DNS) reduction test, the rutin colorimetric method, and the Folin–Ciocalteu method. The morphology, size, and structure of Scu-Au NPs were characterized by TEM, DLS, XRD, and XPS. The photothermal characteristics induced by near-infrared (NIR) irradiation were assessed by continuously monitoring the temperature elevation. The anticancer activity and mechanisms of Scu-Au NPs were investigated using MTT assay, cell uptake studies, ROS level detection, cell apoptosis and necrosis assays, flow cytometry analysis, intracellular Caspase-3 protein activity fluorescence detection, and Western blot analysis on A549, 4T1, and RAW264.7 cells. Results: Scu-Au NPs were successfully fabricated using Scu extract as a reducing agent. The Scu-Au NPs were spherical with a size of 50 nm. During the synthesis process, the levels of reducing sugars, flavonoids, and polyphenols in the Scu extract decreased by 80.8%, 54.3%, and 70.1%, respectively. Scu-Au NPs demonstrated excellent photothermal responsiveness, thermostability, and biocompatibility. For chemo-photothermal anticancer therapy, the cytotoxicity of Scu-Au NPs on 4T1 cells reached approximately 85% upon exposure to 808 nm NIR irradiation. The anticancer activity was attributed to the induction of apoptosis and necrosis, achieved by increasing intracellular ROS levels, causing cell cycle arrest at the S phase, and modulating the expression of apoptosis-related proteins. Discussion: Our synthesized Scu-Au NPs exhibit favorable photothermal conversion characteristics, demonstrating excellent therapeutic efficacy and safety for cancer treatment.

ABSTRACTImportance: Non-suicidal self-injury (NSSI) is a significant mental health issue requiring a deeper understanding of its underlying causes, such as childhood maltreatment, adult bullying victimization, and depression. Previous studies have not adequately addressed the cumulative risks of these factors on NSSI among college students. This population-based study investigates these cumulative risk factors.Design, setting, and participants: The cross-sectional study included 63 university’s college students with a mean age of 19.6 years (N = 95,833).Main outcomes and measures: Two Chi-Square Automatic Interaction Detection (CHAID) decision tree models were used to classify subgroups based on childhood maltreatment and adult bullying victimization experiences and to investigate their cumulative risks of NSSI. Recursive partitioning algorithms determined each predictor variable’s relative importance.Results: The CHAID model accurately predicted NSSI behaviours with an overall accuracy rate of 77.8% for individuals with clinically relevant depressive symptoms and 97.2% for those without. Among depressed individuals, childhood emotional abuse was the strongest NSSI predictor (Chi-Square, 650.747; adjusted P

BackgroundBilateral optic neuritis associated with optic disc swelling is a common feature of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, extensive deep retinal haemorrhages have not been described in the context of MOG-associated optic neuritis. Here, we report a case of infectious mononucleosis with marked binocular peripapillary and perivascular haemorrhages as well as extensive deep retinal haemorrhages in the presence of MOGAD.Case reportA 39-year-old Chinese woman presenting with subacute binocular vision reduction with no light perception was diagnosed with MOGAD. Fundus examination revealed the presence of binocular peripapillary and perivascular haemorrhages as well as extensive deep retinal haemorrhages with severe optic disc swelling greater in the right eye than in the left and dilated and tortuous retinal venules. The patient tested positive for the Epstein–Barr virus (EBV) antigen (595 U/mL) and the EBV capsid antigen (>750 U/mL). She had a fever and right upper quadrant abdominal pain, and a doctor determined splenomegaly 1 week before the onset of orbital pain and decreased vision acuity. Medical history and laboratory tests indicated the presence of concurrent infectious mononucleosis. Other investigational indicators of retinal haemorrhages, including hypertension, diabetes mellitus, vascular disease, systemic lupus erythematosus, metabolic disease, and renal or liver dysfunction, were absent.DiscussionThis case suggests that retinal haemorrhage is a possible complication of infectious mononucleosis in the presence of MOGAD.

Introduction: Traditional Chinese Medicine (TCM) is renowned for its holistic treatment approach and minimal side effects. Luteolin (LUT) and Quercetin (QUE) each possess notable anticancer properties. This study is the first to elucidate the synergistic anticancer activity of the combination of LUT and QUE (LUT+QUE) against lung cancer. Methods: The synergistic anticancer activity of QUE+LUT was evaluated through the combination index (CI) value by varying the concentrations of QUE and LUT. Network pharmacology analysis was then employed to identify the key targets and crucial signaling pathways for QUE and LUT. Finally, the synergistic anticancer mechanisms of QUE+LUT were elucidated by verifying these core targets and pathways through various experiments, including apoptosis assays, migration assays, ELISA, Western blot and reactive oxygen species (ROS) assays. Results: The key targets identify through network pharmacology analysis include BCL2L1, MMP9, JUN, PTGS2, TP53, AKT1 and CASP3. The crucial pathways are the PI3K-Akt signaling pathway and chemically-induce carcinogenic ROS pathways. Cellular experiments demonstrate that QUE+LUT synergistically induce apoptosis, inhibit cell proliferation, migration and invasion, increase ROS levels and regulate the PI3K-Akt signaling pathway, effectively targeting lung cancer cells. Discussion: The combined therapy of QUE and LUT holds potential as an effective treatment for cancer patients, providing valuable insights for the selection and mechanistic exploration of important anticancer drugs.

Abstract Roundabout guidance receptor 2 (Robo2) is closely related to malignant tumors such as pancreatic cancer and liver fibrosis, but there is no relevant research on the role of Robo2 in HCC. The study will further explore the function and mechanism of Robo2 and its downstream target genes in HCC. Firstly, Robo2 protein levels in human HCC tissues and paired adjacent normal liver tissues were detected. Then we established HepG2 and Huh7 hepatoma cell lines with knock-down Robo2 by transfection with lentiviral vectors, and examined the occurrence of EMT, proliferation and apoptosis abilities in HCC cells by western blot, flow cytometry, wound healing assay and TUNEL staining. Then we verified the interaction between Robo2 and its target gene by Co-IP and immunofluorescence co-staining, and further explored the mechanism of Robo2 and YB-1 by rescue study. The protein expression level of Robo2 in HCC was considerably higher than that in the normal liver tissues. After successfully constructing hepatoma cells with knock-down Robo2, it was confirmed that down-regulated Robo2 suppressed EMT and proliferation of hepatoma cells, and accelerated the cell apoptosis. High-throughput sequencing and validation experiments verified that YB-1 was the downstream target gene of Robo2, and over-expression of YB-1 could reverse the apoptosis induced by Robo2 down-regulation and its inhibitory effect on EMT and proliferation. Robo2 deficiency inhibits EMT and proliferation of hepatoma cells and augments the cell apoptosis by regulating YB-1, thus inhibits the occurrence of HCC and provides a new strategy for the treatment of HCC.

The self-quenching fluorogenic probe facilitates precise identification of LAMP (loop-mediated isothermal amplification) amplicons, unaffected by non-specific products resulting from primer dimers. However, low quenching efficiency by surrounding nucleobases leads to high background signal, posing significant challenges for visual inspection with the naked eye. The present study aims to identify an oligonucleotide sequence that is complementary to the self-quenching fluorogenic probe, and to employ the fluorescence super-quenching mechanism of double-stranded DNA to establish a visualization system for the LAMP assay. The results indicated that the incorporation of a sequence fully complementary to the probe could significantly reduce the system’s background fluorescence (p < 0.05). When the melting temperature exceeds room temperature, truncating the complementary sequence from the 3′ end does not compromise the probe’s quenching efficiency. The LAMP visualization system, using a 10–13-base complementary sequence of the loop primer-based probe, could effectively minimize background fluorescence and yield straightforward visual results post-reaction. Applied to rainbow trout and Atlantic salmon detection, the system detected 1 pg DNA in a closed-tube format. In conclusion, a suitable complementary sequence can reduce the background fluorescence of the self-quenching fluorogenic probe. Employing this sequence alongside the self-quenching fluorogenic probe to develop a low-background fluorescence LAMP system demonstrates great potential for successful visual detection and holds considerable promotional merit.

Abiotic stress is one of the key factors harming global agriculture today, seriously affecting the growth and yield of vegetables. Pepper is the most widely grown vegetable in the world, with both high nutritional and economic values. Currently, the increase in global extreme weather events has heightened the frequency of abiotic stresses, such as drought, high and low temperatures, waterlogging, and high salt levels, which impairs pepper growth and development, leading to its reduced yield and quality. In this review, we summarize the research progress on the responses of pepper to abiotic stress in recent years in terms of physiology, biochemistry, molecular level, and mitigation measures. We then explore the existing problems and propose future research directions. This work provides a reference for the cultivation and development of new pepper varieties resistant to abiotic stress.

The substitution of ingredients with Salmonidae, particularly Salmo salar, has led to widespread reports of financial losses and health risks globally, emphasizing the urgent need for the development of a rapid and precise method for species identification. The aim of the present study was to develop a novel method for the rapid screening of Salmonidae ingredients and the accurate detection of S. salar simultaneously using multiplex real-time PCR coupled with melting curve analysis. Specifically, primer sets specific for S. salar and Salmonidae were cross-confirmed. Moreover, the reaction system and conditions of a real-time duplex PCR were optimized, and the proposed methodology was verified, proving that the assay has good specificity and sensitivity. Clear and distinguishable melting peaks, with expected Tm values of around 80 °C (S. salar) and 84 °C (Salmonidae), were observed for twelve products, proving the presence of S. salar. However, four products were not derived from S. salar, but they could have belonged to another species within the Salmonidae family due to the presence of only one specific melting peak at a Tm value of about 84 °C. Therefore, the novel assay in the present study allows for the fast and accurate screening of Salmonidae ingredients and the detection of S. salar simultaneously.

BackgroundHypotension is a risk factor for postoperative complications, but evidence from randomized trials does not support that a higher blood pressure target always leads to optimized outcomes. The heterogeneity of underlying hemodynamics during hypotension may contribute to these contradictory results. Exploring the subtypes of hypotension can enable optimal management of intraoperative hypotension.MethodsThis is a prospective, observational pilot study. Patients who were ≥ 45 years old and scheduled to undergo moderate-to-high-risk noncardiac surgery were enrolled in this study. The primary objective of this pilot study was to investigate the frequency and distribution of perioperative hypotension and its subtypes (hypotension with or without cardiac output reduction). The exposure of hypotension and its subtypes in patients with and without myocardial or acute kidney injury were also explored.ResultsSixty patients were included in the analysis. 83% (50/60) of the patients experienced perioperative hypotension. The median duration of hypotension for each patient was 8.0 [interquartile range, 3.1–23.3] minutes. Reduced cardiac output was present during 77% of the hypotension duration. Patients suffering from postoperative myocardial or acute kidney injury displayed longer duration and more extensive exposure in all hypotension subtypes. However, the percentage of different hypotension subtypes did not differ in patients with or without postoperative myocardial or acute kidney injury.ConclusionPerioperative hypotension was frequently accompanied by cardiac output reduction in moderate-to-high-risk noncardiac surgical patients. However, due to the pilot nature of this study, the relationship between hypotension subtypes and postoperative myocardial or acute kidney injury still needs further exploration.Clinical trial registrationhttps://www.chictr.org.cn/showprojEN.html?proj=134260, CTR2200055929.

ABSTRACTCellulolytic bacteria ferment dietary fiber into short-chain fatty acids, which play an important role in improving fiber utilization and maintaining intestinal health. Safe and effective cellulolytic bacteria are highly promising probiotic candidates. In this study, we isolated three strains of Bacillus cereus, which exhibited cellulolytic properties, from Kele pig feces. To assess the genetic basis of cellulose degradation by the isolates, whole-genome sequencing was used to detect functional genes associated with cellulose metabolism. Subsequently, we identified that the B. cereus CL2 strain was safe in mice by monitoring body weight changes, performing histopathologic evaluations, and determining routine blood indices. We next evaluated the biological characteristics of the CL2 strain in terms of its growth, tolerance, and antibiotic susceptibility, with a focus on its ability to produce short-chain fatty acids. Finally, the intestinal flora structure of the experimental animals was analyzed to assess the intestinal environment compatibility of the CL2 strain. In this study, we isolated a cellulolytic B. cereus CL2, which has multiple cellulolytic functional genes and favorable biological characteristics, from the feces of Kele pigs. Moreover, CL2 could produce a variety of short-chain fatty acids and does not significantly affect the diversity of the intestinal flora. In summary, the cellulolytic bacterium B. cereus CL2 is a promising strain for use as a commercial probiotic or in feed supplement.IMPORTANCEShort-chain fatty acids are crucial constituents of the intestinal tract, playing an important and beneficial role in preserving the functional integrity of the intestinal barrier and modulating both immune responses and the structure of the intestinal flora. In the intestine, short-chain fatty acids are mainly produced by bacterial fermentation of cellulose. Therefore, we believe that safe and efficient cellulolytic bacteria have the potential to be novel probiotics. In this study, we systematically evaluated the safety and biological characteristics of the cellulolytic bacterium B. cereus CL2 and provide evidence for its use as a probiotic.

The fetal liver (FL) is the key erythropoietic organ during fetal development, but knowledge on human FL erythropoiesis is very limited. In this study, we sorted primary erythroblasts from FL cells and performed RNA sequencing (RNA-seq) analyses. We found that temporal gene expression patterns reflected changes in function during primary human FL terminal erythropoiesis. Notably, the expression of genes enriched in proteolysis and autophagy was up-regulated in orthochromatic erythroblasts (OrthoEs), suggesting the involvement of these pathways in enucleation. We also performed RNA-seq of in vitro cultured erythroblasts derived from FL CD34+ cells. Comparison of transcriptomes between the primary and cultured erythroblasts revealed significant differences, indicating impacts of the culture system on gene expression. Notably, the expression of lipid metabolism-related genes was increased in cultured erythroblasts. We further immortalized erythroid cell lines from FL and cord blood (CB) CD34+ cells (FL-iEry and CB-iEry, respectively). FL-iEry and CB-iEry were immortalized at the proerythroblast stage and can be induced to differentiate into OrthoEs, but their enucleation ability was very low. Comparison of the transcriptomes between OrthoEs with and without enucleation capability revealed the down-regulation of pathways involved in chromatin organization and mitophagy in OrthoEs without enucleation capacity, indicating that defects in chromatin organization and mitophagy contribute to the inability of OrthoEs to enucleate. Additionally, the expression of HBE1, HBZ, and HBG2 was up-regulated in FL-iEry compared with CB-iEry, and such up-regulation was accompanied by down-regulated expression of BCL11A and up-regulated expression of LIN28B and IGF2BP1. Our study provides new insights into human FL erythropoiesis and rich resources for future studies.

Abstract Objectives This study aims to evaluate the efficacy of multi-model incorporated by radiomics, deep learning, and transcriptomics features for predicting pathological grade and survival in patients with clear cell renal cell carcinoma (ccRCC). Methods In this study, data were collected from 177 ccRCC patients, including radiomics features, deep learning (DL) features, and RNA sequencing data. Diagnostic models were then created using these data through least absolute shrinkage and selection operator (LASSO) analysis. Additionally, a multi-model was developed by combining radiomics, DL, and transcriptomics features. The prognostic performance of the multi-model was evaluated based on progression-free survival (PFS) and overall survival (OS) outcomes, assessed using Harrell’s concordance index (C-index). Furthermore, we conducted an analysis to investigate the relationship between the multi-model and immune cell infiltration. Results The multi-model demonstrated favorable performance in discriminating pathological grade, with area under the ROC curve (AUC) values of 0.946 (95% CI: 0.912–0.980) and 0.864 (95% CI: 0.734–0.994) in the training and testing cohorts, respectively. Additionally, it exhibited statistically significant prognostic performance for predicting PFS and OS. Furthermore, the high-grade group displayed a higher abundance of immune cells compared to the low-grade group. Conclusions The multi-model incorporated radiomics, DL, and transcriptomics features demonstrated promising performance in predicting pathological grade and prognosis in patients with ccRCC. Critical relevance statement We developed a multi-model to predict the grade and survival in clear cell renal cell carcinoma and explored the molecular biological significance of the multi-model of different histological grades. Key points 1. The multi-model achieved an AUC of 0.864 for assessing pathological grade. 2. The multi-model exhibited an association with survival in ccRCC patients. 3. The high-grade group demonstrated a greater abundance of immune cells. Graphical Abstract

Erythropoiesis occurs first in the yolk sac as a transit “primitive” form, then is gradually replaced by the “definitive” form in the fetal liver (FL) during fetal development and in the bone marrow (BM) postnatally. While it is well known that differences exist between primitive and definitive erythropoiesis, the similarities and differences between FL and BM definitive erythropoiesis have not been studied. Here we performed comprehensive comparisons of erythroid progenitors and precursors at all maturational stages sorted from E16.5 FL and adult BM. We found that FL cells at all maturational stages were larger than their BM counterparts. We further found that FL BFU-E cells divided at a faster rate and underwent more cell divisions than BM BFU-E. Transcriptome comparison revealed that genes with increased expression in FL BFU-Es were enriched in cell division. Interestingly, the expression levels of glucocorticoid receptor Nr3c1, Myc and Myc downstream target Ccna2 were significantly higher in FL BFU-Es, indicating the role of the Nr3c1-Myc-Ccna2 axis in the enhanced proliferation/cell division of FL BFU-E cells. At the CFU-E stage, the expression of genes associated with hemoglobin biosynthesis were much higher in FL CFU-Es, indicating more hemoglobin production. During terminal erythropoiesis, overall temporal patterns in gene expression were conserved between the FL and BM. While biological processes related to translation, the tricarboxylic acid cycle and hypoxia response were upregulated in FL erythroblasts, those related to antiviral signal pathway were upregulated in BM erythroblasts. Our findings uncovered previously unrecognized differences between FL and BM definitive erythropoiesis and provide novel insights into erythropoiesis.

Purpose: To observe the clinical and imaging characteristics of radiation-induced optic neuropathy (RION). Methods: We retrospectively reviewed the clinical data of 43 patients (69 eyes) who were diagnosed with RION at the Chinese PLA General Hospital from 2010 to 2021. Results: The latency from radiotherapy to onset of visual loss ranged from 1 to 132 (36.33 ​± ​30.48) months. Optic disc pallor and optic disc edema were found in 27.0% (10/37) and 8.1% (3/37) of the eyes, respectively, within 2 months. After treatment, the best corrected visual acuity (BCVA) was restored in 24.6% (17/69) of the eyes and the final BCVA improved in 13.0% (9/69) of the eyes. An 82.5% (33/40) of the eyes with magnetic resonance imaging (MRI) showed enhancement of the affected optic nerve, mostly (69.7%) in the intracranial segment, and 36.4% (12/33) of the eyes with expansion and T2-high signals also showed enhancement of the affected optic nerve. The superior retinal nerve fiber layer (RNFL) and the outer circle superior quadrant (OS) of the inner limiting membrane to retinal pigment epithelium (ILM-RPE) layer thinned significantly during the first month. The center of the ILM-RPE layer thickened significantly during the first two months and the inner circle temporal quadrant (IT) of the ILM-RPE layer thickened significantly from the third to sixth month. The RNFL thinned significantly after 6 months except for the temporal quadrant, and the average inner circle superior quadrant (IS) and outer circle of the ILM-RPE layer thinned significantly after 6 months. There was no significant difference between hyperbaric oxygen therapy (HBOT) and high-dose intravenous methylprednisolone (IVMP) therapy in improving BCVA recovery or final BCVA (P ​> ​0.05). Conclusions: The structural damage of the RNFL and ILM-RPE layer occurred during the first month, the RNFL showed progressive thinning during the follow-up period, while the ILM-RPE layer showed thinning during the first month, thickening from the third to sixth month, and thinning after 6 months. There was a discrete region of enhancement of the optic nerve, often with expansion and high-T2 signals on MRI. HBOT and high-dose IVMP therapy were hardly effective for treating RION in the non-acute stage.

Alkaline stress poses a significant challenge to the healthy growth of fish. Ginger polysaccharide (GP) is one of the main active substances in ginger and has pharmacological effects, such as anti-oxidation and immune regulation. However, the physiological regulatory mechanism of GP addition to diet on alkalinity stress in crucian carp remains unclear. This study aimed to investigate the potential protective effects of dietary GP on antioxidant capacity, gene expression levels, intestinal microbiome, and metabolomics of crucian carp exposed to carbonate (NaHCO3). The CK group (no GP supplementation) and COG group (NaHCO3 stress and no GP supplementation) were set up. The GPCS group (NaHCO3 stress and 0.4% GP supplementation) was stressed for seven days. Based on these data, GP significantly increased the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), acid phosphatase (ACP), and alkaline phosphatase (AKP) in carp under alkalinity stress (p < 0.05) and decreased the activity of malon dialdehyde (MDA) (p < 0.05). GP restored the activity of GSH-PX, ACP, and AKP to CK levels. The expression levels of tumor necrosis factor β (TGF-β), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin 8 (IL-8) genes were decreased, and the expression levels of determination factor kappa-B (NF-κB) and interleukin 10 (IL-10) genes were increased (p < 0.05). Based on 16 S rRNA high-throughput sequencing, GP improved the changes in the intestinal microbial diversity and structural composition of crucian carp caused by NaHCO3 exposure. In particular, GP increased the relative abundance of Proteobacteria and Bacteroidetes and decreased the relative abundance of Actinobacteria. The metabolic response of GP to NaHCO3 exposed crucian carp guts was studied using LC/MS. Compared to the COG group, the GPCS group had 64 different metabolites and enriched 10 metabolic pathways, including lipid metabolism, nucleotide metabolism, and carbohydrate metabolism. The addition of GP to feed can promote galactose metabolism and provide an energy supply to crucian carp, thus alleviating the damage induced by alkalinity stress. In conclusion, GP can mitigate the effects of NaHCO3 alkalinity stress by regulating immune function, intestinal flora, and intestinal metabolism in crucian carp. These findings provide a novel idea for studying the mechanism of salt-alkali tolerance in crucian carp by adding GP to feed.

Carbon capture, utilization, and storage (CCUS) are essential technologies for realizing carbon neutrality in the context of fossil fuel decarbonization. Integrated carbon capture and utilization, in conjunction with the reverse water gas shift reaction (ICCU-RWGS), presents a promising strategy for the in-situ conversion of CO2. This approach mitigates the energy penalties associated with CO2 capture and eliminates the additional costs associated with storage and transportation. In this study, we employed a Cu-Al composite catalyst, prepared using the impregnation method, for ICCU-RWGS, with a specific focus on CO2 hydrogenation. The kinetics of hydrogenation for the Cu-Al catalyst were comprehensively investigated using micro-fluidized bed thermogravimetric analysis coupled with mass spectrometry (MFB-TGA-MS). The results indicate that, when subjected to experimental conditions involving 800 °C, 20 vol.% CO2, 30 vol.% H2, and a sample mass of 1 g, the comprehensive evaluation reveals a CO2 conversion rate of 43.67 %. This conversion is accompanied by 100 % CO selectivity and a reaction rate of 0.10 mmol·g−1·s−1, respectively. Furthermore, we calculated the kinetic parameters for the CO2 hydrogenation by analyzing the MFB-TGA-MS data, utilizing the simplified K-L model for fluidized beds. The results indicated an activation energy of 55.8 kJ∙mol−1. These findings highlight the effectiveness of ICCU-RWGS methodologies, especially concerning CO2 hydrogenation, and present a compelling case for their further commercialization.

The green synthesis of gold nanoparticles (Au NPs) using extracts or active ingredients from traditional Chinese medicine presents a novel approach characterized by simplicity, environmental friendliness, and independence from specific conditions. This innovative method combines the photothermal conversion properties of Au NPs with the chemotherapeutic effects of traditional Chinese medicine components, significantly enhancing anticancer efficacy. Celastrol (Cel), an effective medicinal ingredient extracted from the traditional Chinese herb Tripterygium wilfordii Hook. f. (TW), exhibits outstanding anticancer properties. In this study, Cel was successfully employed for the novel green synthesis of gold nanoparticles, forming Cel-Au NPs with a particle size of 50[Formula: see text]nm. Cel-Au NPs demonstrated excellent photothermal responsiveness, thermostability, and biocompatibility. The cytotoxicity of Cel-Au NPs on A549 cells reached approximately 80% upon exposure to 808[Formula: see text]nm near-infrared (NIR) irradiation. The anticancer activity was attributed to the induction of apoptosis and necrosis, achieved by elevating intracellular reactive oxygen species (ROS) levels and modulating the expression of apoptosis-related proteins. In conclusion, our synthesized Cel-Au NPs exhibited exceptional capabilities in chemotherapy and photothermal therapy, demonstrating excellent therapeutic efficacy and safety for cancer treatment.

Mixed-flow pumps, which amalgamate centrifugal and axial-flow attributes, play a pivotal role in various sectors due to their high efficiency and versatility. This paper, utilizing numerical simulation and experimental validation, addresses the critical role of impeller blade count in mixed-flow pump performance. It investigates the effect of the number of impeller blades on the energy dissipation mechanism and inlet flow pattern of a mixed-flow pump. The results reveal that dynamic and static interference effects, along with the separation vortex due to flow separation, are the main sources of energy dissipation in the pump. Under part-load and part-overload conditions, the increase in the number of blades contributes to the improvement of the flow pattern and performance but may induce more intense rotating stall effects under part-load conditions. In overload conditions, the increase in the number of blades significantly amplifies the volume of the inlet vortex structure, consequently deteriorating the inlet conditions of the impeller. This study provides valuable insights for the design and optimization of mixed-flow pumps.

In this study, a non-contact electrical resistivity method is employed to investigate the hydration process of calcium aluminate cement (CAC) pastes incorporating silica fume (SF) at an early age. The CAC-SF pastes have a water-to-binder ratio (w/b) of 0.6 and a replacement of SF for CAC at 0, 5, 10, and 20% (by weight of the binder). The pastes are tested for electrical resistivity, thermal analysis (internal temperature), setting time, and compressive strength, and the hydration products of the pastes are also examined. The results indicate that the evolution of electrical resistivity is closely related to the hydration process of the CAC pastes, and the conversion stage is closely associated with the setting time of pastes. As the increase of SF replacement, the hydration process of CAC pastes was accelerated within 24 h, and the development of compressive strength was hampered at an early age but increased later. SF replacement inhibits the conversion of metastable CAC hydrates (CAH10 and C2AH8) to C3AH6 through filling, seeding, and reacting with CAC, thus reducing the heat of hydration.

Nowadays, digital transformation has become an urgent strategic task for traditional commercial banks. Due to the lack of measurement of banks’ digital transformation, whether digital transformation could enhance the competitiveness of banks is still inconclusive. In this paper, we construct an index system to measure digital transformation of banks from three dimensions: strategy transformation, business transformation and management transformation. Using data from Chinese commercial banks, this paper measures the progress of digital transformation of banks in China. The empirical results show that digital transformation can improve bank performance, reduce the negative impact of new technology entrants, and promote the exit of offline channels.

PurposeAs glial autoantibody testing is not yet available in some areas of the world, an alternative approach is to use clinical indicators to predict which subtypes of middle-aged and elderly-onset optic neuritis (ON) have manifested.MethodThis study was a single-center hospital-based retrospective cohort study. Middle-aged and elderly-onset ON patients (age > 45 years) who had experienced the first episode of ON were included in this cohort. Single- and multi-parametric diagnostic factors for middle-aged and elderly-onset myelin oligodendrocyte glycoprotein immunoglobulin-associated ON (MOG-ON) and aquaporin-4 immunoglobulin-related ON (AQP4-ON) were calculated.ResultsFrom January 2016 to January 2020, there were 81 patients with middle-aged and elderly-onset ON, including 32 (39.5%) AQP4-ON cases, 19 (23.5%) MOG-ON cases, and 30 (37.0%) Seronegative-ON cases. Bilateral involvement (47.4%, P = 0.025) was most common in the MOG-ON group. The presence of other concomitant autoimmune antibodies (65.6%, P = 0.014) and prior neurological history (37.5%, P = 0.001) were more common in the AQP4-ON group. The MOG-ON group had the best follow-up best-corrected visual acuity (BCVA) (89.5% ≤ 1.0 LogMAR, P = 0.001). The most sensitive diagnostic factors for middle-aged and elderly-onset MOG-ON were ‘follow-up VA ≤ 0.1 logMAR’ (sensitivity 0.89), ‘bilateral involvement or follow-up VA ≤ 0.1 logMAR’ (sensitivity 0.95), ‘bilateral involvement or without neurological history’ (sensitivity 1.00), and ‘follow-up VA ≤ 0.1 logMAR or without neurological history’ (sensitivity 1.00), and the most specific factor was ‘bilateral involvement’ (specificity 0.81). The most sensitive diagnostic factors for middle-aged and elderly-onset AQP4-ON were ‘unilateral involvement’ (sensitivity 0.88), ‘unilateral involvement or neurological history’ (sensitivity 0.91), and ‘unilateral involvement or other autoimmune antibodies’ (sensitivity 1.00), and the most specific factor was neurological history (specificity 0.98).ConclusionBased on our cohort study of middle-aged and elderly-onset ON, MOG-ON is less prevalent than AQP4-ON and Seronegative-ON. Using multiple combined parameters improves the sensitivity and negative predictive value for diagnosing middle-aged and elderly-onset MOG-ON and AQP4-ON. These combined parameters can help physicians identify and treat middle-aged and elderly-onset ON early when glial autoantibody status is not available.

BackgroundDecreased handgrip strength (HGS) and activities of daily living (ADL) disability are common in aging populations. No studies have evaluated the bidirectional associations between HGS and ADL disability. This study aimed to explore the bidirectional effects of HGS and ADL disability.MethodsThis study analyzed data from two waves (2011 and 2015) of China Health and Retirement Longitudinal Study (CHARLS). Low HGS is defined by the Asian Working Group for Sarcopenia criteria. Meanwhile, disability was assessed by ADLs scale. The prospective bidirectional association between HGS and ADL disability was examined using binary logistic regression. Subgroup analysis were performed according to age and gender.ResultsA total of 4,902 and 5,243 participants were included in the Stage I and Stage II analyses, respectively. On the one hand, low HGS was significantly associated with subsequent ADL disability. The odds ratio (OR) value of developing BADL disability and IADL disability were 1.60 (95% confidence interval (CI): 1.23–2.08) and 1.40 (95% CI: 1.15–1.70), respectively, in participants with low HGS. On the other hand, baseline ADL disability was associated with an increased risk of developing low HGS. The OR value of developing low HGS were 1.84 (95% CI: 1.34–2.51) and 1.46 (95% CI: 1.19–1.79) for participants with BADL disability and participants with IADL disability, respectively. Lastly, the strength of the bidirectional associations varied among subgroups.ConclusionsA significant bidirectional associations were identified between HGS and ADL disability. Interventions should be developed to prevent the development or progression of both low HGS and ADL disability.

The use of artificial substrates and biofloc technology can favor fish culture and improve water quality. The aim of this study was to evaluate whether artificial substrates and carbon source additions modify the microbial activity of water bodies. The diversity and structure of microflora in the water after adding artificial substrates and carbon sources to the ponds were analyzed using high-throughput sequencing based on the V3-V4 region of 16S rRNA genes. The results showed that there was no difference in the richness and diversity of intestinal microflora between the control and experimental groups. Principal coordinate analysis (PCoA) and nonmetric multidimensional scaling (NMDS) showed that artificial substrate and carbon source addition changed the structure of the microflora. The results of a linear discriminant analysis (LDA) effect size (LefSe) indicated 11 biomarkers in the EGˍst group. Spearman correlation heatmap analysis showed that environmental factors affected the bacterial communities, and the results of a redundancy analysis indicated that chemical oxygen demand was a critical factor in controlling the bacterial communities in the water. These results provide an understanding of the effect of artificial substrate and carbon source addition on bacterial diversity and community composition in water.

Saline–alkaline aquaculture has become an important breakthrough in expanding the space available for aquaculture in China. However, the biochemical composition and quality of Eriocheir sinensis reared in carbonate alkalinity water are still unclear. Therefore, this study investigated the edible yield, coloration, and nutritional and flavor quality of Eriocheir sinensis. A significantly lower gonadosomatic index (GSI), meat yield (MY), and total edible yield (TEY) were detected in intensive pond (IP) samples than those in semi-intensive reed wetland (SIWR) (p < 0.05). Six color parameters in the hepatopancreas (p < 0.05) differed between IP and SIRW. The contents of crude protein and fat in the female hepatopancreas of IP were significantly higher than those in SIRW (p < 0.05). The concentrations of total monounsaturated fatty acids (∑MUFA), total essential fatty acids (∑EFA), and hypocholesterolaemic/hypercholesterolaemic ratio (h/H) in the female edible tissues checked were higher in IP than those in SIRW, with significant differences including ∑MUFA in the hepatopancreas and ovary, ∑EFA in the muscle, and h/H in the ovary (p < 0.05). Higher total free amino acid (∑FAA) contents of muscle were detected in SIRW than that in IP samples. Significantly higher K, Ca, Mg, Fe, and Zn contents in the ovary were detected in SIRW samples compared to IP (p < 0.05). Overall, Eriocheir sinensis reared in carbonate-alkalinity water is an important source of nutrients.

Background: Evidence regarding the association between anemia and sarcopenia in the elderly population is limited and controversial. The purpose of this study was to investigate the association between anemia and sarcopenia in Chinese elderly. Methods: The cross-sectional study used the third wave of data from the China Longitudinal Study of Health and Retirement (CHARLS). Participants were classified as sarcopenic versus non-sarcopenic according to the guidelines developed by the Asian Working Group for Sarcopenia (AWGS) 2019. Meanwhile, participants were defined for anemia using World Health Organization criteria. Logistic regression models were conducted to assess the association between anemia and sarcopenia. Odds ratios (OR) were reported to indicate the strength of the association. Results: A total of 5016 participants were included in the cross-sectional analysis. The overall prevalence of sarcopenia in this population was 18.3 %. After adjusting for all potential risk factors, anemia and sarcopenia were independently associated (OR = 1.43, 95 % CI 1.15–1.77, P = 0.001). In terms of subgroups, the association of anemia with sarcopenia was also significant in people over 71 years of age (OR = 1.93, 95 % CI 1.40–2.66, P

Summary: Dynamic regulation of integrin activation and inactivation is critical for precisely controlled cell adhesion and migration in physiological and pathological processes. The molecular basis for integrin activation has been intensively studied; however, the understanding of integrin inactivation is still limited. Here, we identify LRP12 as an endogenous transmembrane inhibitor for α4 integrin activation. The LRP12 cytoplasmic domain directly binds to the integrin α4 cytoplasmic tail and inhibits talin binding to the β subunit, thus keeping integrin inactive. In migrating cells, LRP12-α4 interaction induces nascent adhesion (NA) turnover at the leading-edge protrusion. Knockdown of LRP12 leads to increased NAs and enhanced cell migration. Consistently, LRP12-deficient T cells show an enhanced homing capability in mice and lead to aggravated chronic colitis in a T cell-transfer colitis model. Altogether, LRP12 is a transmembrane inactivator for integrins that inhibits α4 integrin activation and controls cell migration by maintaining balanced NA dynamics.

Background: Infliximab (IFX) is the first-line treatment for Crohn's disease (CD). However, the secondary loss of response (LOR) is common in IFX therapy. Therefore, non-invasive assessment of LOR in CD patients is the goal pursued by clinicians. Methods: A multicenter study involving 181 CD patients was conducted, with patients being split into a training cohort (n = 102), testing cohort (n = 45), and validation cohort (n = 34). The study evaluated various clinical factors to establish a clinical model, and a radiomics signature was constructed based on reproducible features from computed tomography enterography (CTE). Logistic regression modeling was used to create models based on the radiomics signature and significant clinical factors, with the receiver operating characteristic curve (ROC) used to compare their performance. Results: The study found that 64 of the 181 CD patients included experienced secondary LOR. The radiomics signature performed well in predicting secondary LOR, showing good discrimination in the training cohort (AUC [area under the curve], 0.947; 95% confidence interval [CI], 0.910–0.976), the testing cohort (AUC, 0.860; 95% CI, 0.768–0.941), and the validation cohort (AUC, 0.921; 95% CI: 0.831–1.000). Decision curve analysis (DCA) demonstrated the clinical value of the radiomics nomogram. Conclusions: The CTE-based radiomics model showed good performance in predicting secondary LOR in CD patients. The nomogram can help clinicians choose alternative biologics early for CD patients.

Abstract In this paper, a cyber‐physical description of mixed traffic that can reflect the interaction between vehicles is first proposed. By treating vehicles as nodes and the cyber‐physical interaction between vehicles as directed edges between nodes, the network of vehicles in traffic is obtained. The small‐world and scale‐free characteristics of mixed traffic are found under this description. Then the CPS‐based pinning approach for achieving indirect control of HVs is proposed. Besides the control algorithm of pinning nodes, the impact of the spatial distribution of automated vehicles on traffic is studied. The approach is compatible with the existing control of automated vehicle in mixed vehicle platoon. Numerical simulation results under three‐lane scenario illustrated the effectiveness of the proposed pinning approach.

In this paper, the pairwise comparison matrix (PCM) of the best-worst method (BWM) is regarded as a special incomplete PCM (IPCM), and an improved method based on the optimal completion of the IPCM, called BWM-IPCM, is proposed. Firstly, as a special IPCM, BWM-IPCM has been proven to be effective/acceptable and ordinally consistent. Then, with the best consistency as the objective function, the optimization model of BWM-IPCM is established to achieve the optimal completion of incomplete elements, and the optimal weights and rankings are obtained from the completed PCM. In order to deal with possible inconsistencies in BWM, two methods are proposed: one is to invite experts to supplement a small amount of comparison information among inconsistent criteria found; the other is to fine-tune known elements to improve consistency without the participation of experts. Finally, illustrative examples show that compared with the original BWM, the proposed method can make more effective use of additional comparison information, has better consistency description and interpretation, and is easier to solve.

BackgroundC-X-C motif chemokine 12 (CXCL12) is a chemokine that performs many functions. Studies have shown that CXCL12 can aggravate inflammatory symptoms in the central nervous system (CNS). Evidence also indicates that CXCL12 can promote the repair of myelin sheaths in the CNS in experimental autoimmune encephalomyelitis (EAE). Here, we investigated the function of CXCL12 in CNS inflammation by upregulating CXCL12 in the spinal cord and subsequently inducing EAE.Materials and methodsCXCL12 upregulation in the spinal cords of Lewis rats was induced by the injection of adeno-associated virus 9 (AAV9)/eGFP-P2A-CXCL12 after intrathecal catheter implantation. Twenty-one days after AAV injection, EAE was induced and clinical score was collected; Immunofluorescence staining, WB and LFB-PAS staining were used to evaluate the effect of CXCL12 upregulation. In the in vitro study, oligodendrocyte precursor cells (OPCs) were harvested, cultured with CXCL12 and AMD3100, and subjected to immunofluorescence staining for functional assessment.ResultsCXCL12 was upregulated in the lumbar enlargement of the spinal cord by AAV injection. In each stage of EAE, upregulation of CXCL12 significantly alleviated clinical scores by inhibiting leukocyte infiltration and promoting remyelination. In contrast, the addition of AMD3100, which is a CXCR4 antagonist, inhibited the effect of CXCL12. In vitro, 10 ng/ml CXCL12 promoted the differentiation of OPCs into oligodendrocytes.ConclusionAAV-mediated upregulation of CXCL12 in the CNS can alleviate the clinical signs and symptoms of EAE and significantly decrease the infiltration of leukocytes in the peak stage of EAE. CXCL12 can promote the maturation and differentiation of OPCs into oligodendrocytes in vitro. These data indicate that CXCL12 effectively promotes remyelination in the spinal cord and decreases the signs and symptoms of EAE.

Neuromyelitis optica spectrum disorder (NMOSD), a severe demyelinating disease, is rare among children. Plasma exchange (PE) is widely used as a salvage therapy for severe and corticosteroid-unresponsive patients with NMOSD. Presently, there are limited studies on the safety and efficacy of PE in children with NMOSD. Herein, we report the case of six children with NMOSD who received PE along with the outcomes and adverse events. All six children (female, age at onset 4 years 9 months–13 years 2 months) were AQP4-IgG positive and received standard PE using the COM.TEC Cell Separator. The interval between NMOSD onset and PE was 29 days (range 10–98). Only one patient (P3) who received PE 10 days after acute exacerbations exhibited clinical improvement. Her left visual acuity increased from 0.06 to 0.6 (spectacle-corrected visual acuity was 1.0) and her EDSS score decreased from 4 to 3 points. The other five patients had no clinical improvement and no EDSS scores changes after PE. Adverse events included rashes (P1, P3), acute non-occlusive thrombosis of the internal jugular vein (P1), and thrombocytopenia (P2). In conclusion, the timing of PE initiation as a rescue therapy for severe and corticosteroid-unresponsive pediatric AQP4-IgG positive NMOSD may be crucial to treatment efficacy, and early initiation of PE may be associated with a better outcome. Furthermore, PE has the potential risk for clinically significant adverse effects that should be considered before initiating the therapy and should be weighed against potential benefits.

Abstract Background Early identification of the occurrence of arrhythmia in patients with acute myocardial infarction plays an essential role in clinical decision-making. The present study attempted to use machine learning (ML) methods to build predictive models of arrhythmia after acute myocardial infarction (AMI). Methods A total of 2084 patients with acute myocardial infarction were enrolled in this study. (All data is available on Github: https://github.com/wangsuhuai/AMI-database1.git) . The primary outcome is whether tachyarrhythmia occurred during admission containing atrial arrhythmia, ventricular arrhythmia, and supraventricular tachycardia. All data is randomly divided into a training set (80%) and an internal testing set (20%). Apply three machine learning algorithms: decision tree, random forest (RF), and artificial neural network (ANN) to learn the training set to build a model, then use the testing set to evaluate the prediction performance, and compare it with the model built by the Global Registry of Acute Coronary Events (GRACE) risk variable set. Results Three ML models predict the occurrence of tachyarrhythmias after AMI. After variable selection, the artificial neural network (ANN) model has reached the highest accuracy rate, which is better than the model constructed using the Grace variable set. After applying SHapley Additive exPlanations (SHAP) to make the model interpretable, the most important features are abnormal wall motion, lesion location, bundle branch block, age, and heart rate. Among them, RBBB (odds ratio [OR]: 4.21; 95% confidence interval [CI]: 2.42–7.02), ≥ 2 ventricular walls motion abnormal (OR: 3.26; 95% CI: 2.01–4.36) and right coronary artery occlusion (OR: 3.00; 95% CI: 1.98–4.56) are significant factors related to arrhythmia after AMI. Conclusions We used advanced machine learning methods to build prediction models for tachyarrhythmia after AMI for the first time (especially the ANN model that has the best performance). The current study can supplement the current AMI risk score, provide a reliable evaluation method for the clinic, and broaden the new horizons of ML and clinical research. Trial registration Clinical Trial Registry No.: ChiCTR2100041960.

ObjectiveThis study aimed to investigate the clinical spectra and outcomes in pregnancy-related optic neuritis (ON).MethodsWe analyzed the clinical subtype and prognosis of women with pregnancy-related ON in the neuro-ophthalmology department of the First Medical Center at the Chinese PLA General Hospital from January 2014 to December 2019.ResultsA total of 54 patients, including 21 (38.9%) with idiopathic ON (ION), 27 (50.0%) with aquaporin-4 (AQP4)-ON, and 6 (11.6%) with myelin oligodendrocyte glycoprotein (MOG)-ON, who experienced 58 informative pregnancies and 67 episodes of pregnancy-related ON were assessed. Among the ON attacks, there were 11 (16.4%) during pregnancy and 56 (83.6%) within 1 year postpartum (PP1) or after abortion, including 33 (49.3%) in the first trimester. In total, 14 (25.9%) patients with ON onset before pregnancy had a higher relapse rate during PP1 than within 1 year before pregnancy (p = 0.021), and 24 (85.7%) eyes with ION and nine (100%) with MOG-ON had significantly better visual outcomes (p ≥ 0.5) than those with AQP4-ON (14, 35%) (p < 0.001 and p < 0.001, respectively). Two AQP4-ON patients had premature birth and low baby weight, respectively. There were no birth defects or stillbirths.ConclusionThe significantly increased relapse rate and numerous cases of ON after pregnancy suggest that delivery adversely affects the course of ON.

PurposeWe aimed to investigate the refractive status and prevalence of refractive error, as well as its characteristics in Chinese preschool children aged 1–6 years old.MethodsA population-based cross-sectional study—Changsha Children Eye Study (CCES) was conducted. The prevalence of refractive errors among children aged 1–6 years old from 18 community health service centers was surveyed. A handheld child vision screener, Suowei, was used for examination.ResultsA total of 43,105 preschool children were included. The mean spherical equivalent (SE) was 0.42 ± 1.05 D for the right eyes. The mean astigmatism (diopter of cylinder, DC) was −0.83 ± 1.02 D for the right eyes. The magnitude of refractive error was lower in older children, indicating the ongoing of the emmetropization during the 1–6-year-old children. The prevalence of myopia (SE ≤ −1.00 D), hyperopia (SE ≥ +2.00 D) and astigmatism (DC ≥1.50 D) was 2.94, 13.8 and 17.6%, respectively. The prevalence of myopia decreased with the increase of age between the six age groups (P < 0.001). The prevalence of hyperopia was lower in 5–6 years old, whereas, the prevalence of myopia was slightly higher at this period of time. With-the-rule (WTR) astigmatism (+ cylinder axis 90° ± 15°) was the most prevalent type of astigmatism than against-the-rule (ATR) astigmatism (+ cylinder axis 180° ± 15°) and oblique (OBL) astigmatism (X2 = 209.5, P < 0.001). The binary logistic regression model showed that older age and suffering astigmatism were independently associated with the development of myopia. In addition, there was no significant gender difference in the prevalence of myopia, emmetropia, and hyperopia.ConclusionsOur population-based cross-sectional study investigated the prevalence of myopia, hyperopia, and astigmatism in preschool children aged 1–6 years old. The distribution of the refractive error was disperse in the younger group and gradually turned more centralized in older group. Similar to hyperopia, with age increased, the prevalence of myopia was lower in preschool children younger than 5 years old and then slightly increased at 5–6 years, which may indicate an early sign of myopia in school-age children. Therefore, we emphasize that more attention should be given to the children at this age.

Background: Monoclonal antibodies such as rituximab (RTX), eculizumab, inebilizumab, satralizumab, and tocilizumab have been found to be effective therapies for neuromyelitis optica spectrum disease ​(NMOSD) in several clinical randomized controlled trials. Objective: The purpose of this meta-analysis of randomized controlled trials was to assess the efficacy and safety of monoclonal antibodies in the treatment of NMOSD. Methods: We searched the following databases for relevant English language literature from the establishment of the database to June 2021: PubMed, Embase, Cohorane Library, the Central Register of Controlled Trials (CENTRAL), and Web of Science. Randomized controlled trials of monoclonal antibodies were the targets of the review. Results: We included seven trials containing 775 patients (485 in the monoclonal antibody group and 290 in the control group). Patients in the monoclonal group (HR 0.24, 95% CI: 0.14 to 0.40, P ​

Objective: Due to limited imaging conditions, the quality of fundus images is often unsatisfactory, especially for images photographed by handheld fundus cameras. Here, we have developed an automated method based on combining two mirror-symmetric generative adversarial networks (GANs) for image enhancement. Methods: A total of 1047 retinal images were included. The raw images were enhanced by a GAN-based deep enhancer and another methods based on luminosity and contrast adjustment. All raw images and enhanced images were anonymously assessed and classified into 6 levels of quality classification by three experienced ophthalmologists. The quality classification and quality change of images were compared. In addition, image-detailed reading results for the number of dubiously pathological fundi were also compared. Results: After GAN enhancement, 42.9% of images increased their quality, 37.5% remained stable, and 19.6% decreased. After excluding the images at the highest level (level 0) before enhancement, a large number (75.6%) of images showed an increase in quality classification, and only a minority (9.3%) showed a decrease. The GAN-enhanced method was superior for quality improvement over a luminosity and contrast adjustment method (P＜0.001). In terms of image reading results, the consistency rate fluctuated from 86.6% to 95.6%, and for the specific disease subtypes, both discrepancy number and discrepancy rate were less than 15 and 15%, for two ophthalmologists. Conclusions: Learning the style of high-quality retinal images based on the proposed deep enhancer may be an effective way to improve the quality of retinal images photographed by handheld fundus cameras.

Traditional Chinese medicines (TCMs) Tripterygium wilfordii Hook. f. (TW) and Scutellaria barbata D. Don (SB) are reported to have anticancer activity. However, the synergetic anti-liver cancer efficacy is still unknown. Herein, we demonstrated that the combination of TW and fermentation product of SB by yeast (TW+SB) could markedly improve the HepG2 cell suppression capacity as compared to individual TW or SB. Hence, synergetic mechanisms of TW+SB combination were further investigated by systems pharmacology, LC-MS, etc. The results showed that fermentation increases the concentration of active components of SB rather than those of TW, leading to the increase of HepG2 cell inhibition efficacy of SB. TW+SB combination effectively suppresses proliferation, migration, and invasion of liver cancer cells by inducing EGFR/PI3K/Akt signaling pathway mediated apoptosis. In conclusion, TW+SB combination showed outstanding synergetic anti-liver cancer effect, and it might offer a promising treatment option for cancer patients.

The toxicity of ammonia nitrogen (AN) has always caused severe harm to aquatic animals in intensive aquaculture conditions, especially in saline-alkali aquaculture waters. The application of AN removal bacteria is a safe and effective method for controlling the AN concentration in aquaculture water through direct conversion to bacterial protein. However, there is still a lack of AN removal bacteria that are appropriate for saline-alkali aquaculture conditions. In this study, three AN removal strains, namely, Bacillus idriensis CT-WN-B3, Bacillus australimaris CT-WL5-10, and Pseudomonas oleovorans CT-WL5-6, were screened out under alkaline conditions from the alkali-tolerant strains distributed in carbonate saline-alkali soil and water environments in Northeast China. Under different pH (8.0–9.0), salinities (10–30 g/L NaCl), alkalinities (10–30 mmol/L NaHCO3), and AN concentrations (1–3 mg/L), corresponding to the actual conditions of saline-alkali aquaculture waters, the AN removal rates and relative characteristics of these strains were analyzed. The results showed that all of the three strains were efficient on AN removal under various conditions, and the highest removal rate reached up to 3 × 10–13 mg/cfu/h. Both CT-WL5-10 and CT-WL5-6 were most efficient under pH 9.0 with 3 mg/L initial AN, while pH 8.5 with 2 mg/L AN was the best fit for CT-WN-B3. In 96-h pure incubation of these strains in alkali media, approximately 90% AN was removed, and pH values were decreased by 2.0 units within 12 h accompanied by the growth of the strains. In addition, salinity and alkalinity slightly disturbed the removal rates of CT-WL5-10 and CT-WL5-6, but there were at least 65% AN removed by them within 24 h. These results indicated that all three strains have good application prospect in saline-alkali aquaculture waters.

Abstract Acute myocardial infarction (MI) resulting from coronary ischemia is a major cause of disability and death worldwide. Transplantation of human embryonic stem cell (hESC)‐derived cardiovascular progenitor cells (hCVPCs) promotes the healing of infarcted hearts by secreted factors. However, the hCVPC‐secreted proteins contributing to cardiac repair remain largely unidentified. In this study, we investigated protective effects of neurotrophin (NT)‐3 secreted from hCVPCs in hearts against myocardial ischemia/reperfusion (I/R) injury and explored the underlying mechanisms to determine the potential of using hCVPC products as a new therapeutic strategy. The implantation of hCVPCs into infarcted myocardium at the beginning of reperfusion following 1 hour of ischemia improved cardiac function and scar formation of mouse hearts. These beneficial effects were concomitant with reduced cardiomyocyte death and increased angiogenesis. Moreover, hCVPCs secreted a rich abundance of NT‐3. The cardioreparative effect of hCVPCs in the I/R hearts was mimicked by human recombinant NT‐3 (hNT‐3) but canceled by NT‐3 neutralizing antibody (NT‐3‐Ab). Furthermore, endogenous NT‐3 was detected in mouse adult cardiomyocytes and its level was enhanced in I/R hearts. Adenovirus‐mediated NT‐3 knockdown exacerbated myocardial I/R injury. Mechanistically, hNT‐3 and endogenous NT‐3 inhibited I/R‐induced cardiomyocyte apoptosis through activating the extracellular signal‐regulated kinase (ERK) and reducing the Bim level, resulting in the cardioreparative effects of infarcted hearts together with their effects in the improvement of angiogenesis. These results demonstrate for the first time that NT‐3 is a cardioprotective factor secreted by hCVPCs and exists in adult cardiomyocytes that reduces I/R‐induced cardiomyocyte apoptosis via the ERK‐Bim signaling pathway and promotes angiogenesis. As a cell product, NT‐3 may represent as a noncell approach for the treatment of myocardial I/R injury.

Here, the authors show that single upconversion nanoparticles can generate position-sensitive patterns in the spatial domain when placed on a mirror. They attribute this to the single emitter’s interference with its own mirror image and show how this can be used to obtain axial localisation of the particle.

A 12-week rearing trial was carried out to estimate effects on the growth performance, physicochemical indexes, quality, and the molecular expression of Yellow River Carp (Cyprinus carpio haematopterus) using five practical diets, including dietary protein levels of 220, 250, 280, 310, and 340 g/kg. The results illustrated that the fish’s weight gain (WG) and specific growth rate (SGR) were significantly influenced, with an ascending dietary protein level of up to 250 g/kg (p < 0.05). The carp muscle contents of total saturated fatty acids (∑SFA), monounsaturated fatty acids (∑MUFA), polyunsaturated fatty acids (∑PUFA), and fatty acids (∑FA) decreased significantly with the ascending dietary protein levels, except for the 250 g/kg protein diet (p < 0.05). Only the glutamic acid and total essential amino acid (∑EAA) contents were significantly influenced by the ascending dietary protein levels (p < 0.05). The relative GH expression of the carp muscle significantly decreased with the increase in the dietary protein level up to 310 g/kg, and then it significantly increased (p < 0.05). In the intestines, the peak relative TOR expression was observed on the 220 g/kg protein diet, while the relative 4EBP1 expression was significantly influenced by the dietary protein level up to 250 g/kg (p < 0.05). In the muscle, the peak relative TOR and 4EBP1 expression levels were observed on the 250 g/kg protein diet. In gills, the lowest relative Rhag, Rhbg, and Rhcg1 expression levels were observed on the 250 g/kg protein diet. Based on all of the aforementioned results, the optimal dietary protein level for Cyprinus carpio haematopterus (160.24 ± 15.56 g) is 250–280 g/kg.

ObjectivesTo construct a contrast-enhanced CT-based radiomics nomogram that combines clinical factors and a radiomics signature to distinguish papillary renal cell carcinoma (pRCC) type 1 from pRCC type 2 tumours.MethodsA total of 131 patients with 60 in pRCC type 1 and 71 in pRCC type 2 were enrolled and divided into training set (n=91) and testing set (n=40). Patient demographics and enhanced CT imaging characteristics were evaluated to set up a clinical factors model. A radiomics signature was constructed and radiomics score (Rad-score) was calculated by extracting radiomics features from contrast-enhanced CT images in corticomedullary phase (CMP) and nephrographic phase (NP). A radiomics nomogram was then built by incorporating the Rad-score and significant clinical factors according to multivariate logistic regression analysis. The diagnostic performance of the clinical factors model, radiomics signature and radiomics nomogram was evaluated on both the training and testing sets.ResultsThree validated features were extracted from the CT images and used to construct the radiomics signature. Boundary blurring as an independent risk factor for tumours was used to build clinical factors model. The AUC value of the radiomics nomogram, which was based on the selected clinical factors and Rad-score, were 0.855 and 0.831 in the training and testing sets, respectively. The decision curves of the radiomics nomogram and radiomics signature in the training set indicated an overall net benefit over the clinical factors model.ConclusionRadiomics nomogram combining clinical factors and radiomics signature is a non-invasive prediction method with a good prediction for pRCC type 1 tumours and type 2 tumours preoperatively and has some significance in guiding clinicians selecting subsequent treatment plans.

PurposeThe purpose of this study was to investigate pain and radiological features of different types of first-episode demyelinating optic neuritis (ON).MethodsEighty-three patients presenting with first-episode aquaporin-4 (AQP4) antibody-associated ON (AQP4-ON; n = 28), myelin oligodendrocyte glycoprotein (MOG) antibody-associated ON (MOG-ON; n = 26) and idiopathic demyelinating optic neuritis (IDON, n = 29) were included in this retrospective case-control study. We assessed optic nerve lesions on magnetic resonance imaging (MRI), acute pain associated with onset of optic neuritis and clinical characteristics of those ON patients with different serum autoantibody status.Results24 AQP4-ON patients (85.75%), 23 MOG-ON patients (88.5%) and 24 IDON patients (82.8%) suffered from ON-associated pain. MOG-ON had mostly retro-orbital pain; AQP4-ON and IDON had mostly neuropathic pain. In addition, pain was more severe in AQP4ON patients than in other ON patients. In MRI, bilateral involvement was more common in AQP4-ON than IDON (26.9 and 3.7%); radiological optic nerve head swelling was more common in MOG-ON than in AQP4-ON and IDON (68.0 vs. 23.1 vs. 25.9%). MRI lesion in peri-optic nerve sheath was more common in AQP4-ON (53.8 vs. 16.0 vs. 3.7%). In 70 patients with ON-associated pain, gadolinium enhancement of orbital optic nerve was most common in MOG-ON patients (82.4 vs. 55.0 vs. 33.3%, P = 0.018), and enhancement of optic chiasma was most common in AQP4-ON patients (40.0 vs. 5.9 vs. 6.7%, P = 0.015). Perineural and orbital enhancement was observed only in patients with MOG-ON (P < 0.001). The length of enhancement was longer in AQP4-ON patients than in MOG-ON and IDON patients.ConclusionPain is a common symptom in patients with all types of demyelinating ON. AQP4-ON is frequently associated with severe ON-associated pain and longitudinally extensive optic nerve inflammatory lesions. Intra-orbital and peri-optic inflammation were more frequently observed in patients with MOG-ON, which was closely related to optic disc swelling and retro-orbital pain provoked by eye movements.

AimTo evaluate the vision-related quality of life (QOL) in patients with atypical optic neuritis through the 39-item National Eye Institute Visual Function Questionnaire (NEI VFQ-39).MethodsFifty-seven patients with atypical optic neuritis were scheduled in the research unit from June 1 to December 31, 2019. Besides collecting the clinical data, NEI VFQ-39, the Chinese version, was applied to all subjects. The NEI VFQ-39 subscale item scores were compared among subgroups divided by different classifications, and a correlation analysis of the NEI VFQ-39 scores and best-corrected visual acuity (BCVA) for better-seeing and worse-seeing eyes was performed.ResultsThe mean age of scheduled patients was 34.3 ± 12.4 years, with the majority being female (70.2%). The mean composite score was 58.62 ± 17.62. Twenty-nine (50.9%) patients were affected binocularly, and the most subscale scores and composite scores of binocular incidences were lower than those of monocular incidence significantly. However, there was no statistically significant difference in composite scores between patients with and without periocular pain. The patients with worse BCVA in the better-seeing eye have lower scores than those with better BCVA in the better-seeing eye. Most NEI VFQ-39 scores have strong correlations with the BCVA for better-seeing and worse-seeing eyes.ConclusionAtypical optic neuritis has a significant and comprehensive influence on patients' visual function outcomes and quality of life associated with vision. Improving their BCVA in the better-seeing eye can improve their vision-related QOL.