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Introduction: Lecithin cholesterol acyltransferase (LCAT) plays a crucial role in acyl-esterifying cholesterol in plasma, which is essential for reverse cholesterol transport (RCT). Previous studies indicated that its activity on both α and β lipoproteins interpret its effects on lipoproteins for many controversial investigations of atherosclerosis. Objectives: To better understand the relationship between LCAT, diet-induced dyslipidemia and atherosclerosis, we developed a double knockout (LCAT−/−&LDLR−/−, DKO) hamster model to evaluate the specific role of LCAT independent of LDL clearance effects. Methods: Plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and free cholesterol (FC) levels were measured using biochemical reagent kits. FPLC was performed to analyze the components of lipoproteins. Apolipoprotein content was assessed using western blotting (WB). The hamsters were fed a high cholesterol/high fat diet (HCHFD) to induce atherosclerosis. Oil Red O staining was employed to detect plaque formation. Peritoneal macrophages were studied to investigate the effects of LCAT on cholesterol uptake and efflux. Results: On HCHFD, DKO hamsters exhibited significantly elevated levels of TG and FC, while HDL-C was nearly undetectable without affecting TC levels, as compared to low-density lipoprotein receptor (LDLR)-deficient (LDLR−/−, LKO) hamsters. Lipoprotein profiling revealed a marked increase in plasma chylomicron/very low-density lipoprotein (CM/VLDL) fractions, along with an unexpected reduction in LDL fraction in DKO hamsters. Furthermore, DKO hamsters displayed aggravated atherosclerotic lesions in the aorta, aortic root, and coronary artery relative to LKO hamsters, attributed to a pro-atherogenic lipoprotein profile and impaired cholesterol efflux in macrophages. Conclusions: Our study demonstrates the beneficial role of LCAT in inhibiting atherosclerotic development and highlights the distinctive lipid metabolism characteristics in hamsters with familial hypercholesterolemia.

Abstract Since October 2023, a significant outbreak of Mycoplasma Pneumoniae Pneumonia (MPP) has been observed in children in northern China. Chinese health authorities have attributed this epidemiological to immune debt resulting from the relaxation of coronavirus disease 2019 (COVID-19) control measures. This study described the epidemiological features of Mycoplasma pneumoniae (MP) prevalence in children and developed a straightforward prediction model to differentiate between MPP and viral pneumonia in children. The infection rate of MP in children notably increased from 8.12 in 2022 to 14.94% in 2023, peaking between October and November, especially among school-age children. Logistic regression screening identified four key indicators: Age, D-Dimer levels, erythrocyte sedimentation rate, and gender. The developed nomogram exhibited a receiver operator characteristic curve-area under the curve (ROC-AUC) of 0.858, with external validation confirming an ROC-AUC of 0.794. This study examined the epidemiological characteristics of MPP prevalence in children in Shandong Province during and after the COVID-19 pandemic. An early predict model was developed and validated to differentiate between Mycoplasma Pneumoniae and viral infections.

Abstract Background The objective of this study is to illustrate the changes in the choroidal vasculature in individuals with diffuse chorioretinal atrophy (DCA, early-stage myopic maculopathy) and investigate the association between them. Methods This study included 1418 highly myopic eyes from 720 participants aged 18 − 60 years from the Wenzhou High Myopia Cohort Study. These participants underwent comprehensive ophthalmic assessments. Myopic maculopathy classification followed the Meta-PM system, with pathological myopia defined as myopic maculopathy of DCA or severer. Eyes with myopic maculopathy categorized as no macular lesions (C0), tessellated fundus (C1), and DCA (C2) were enrolled in the analysis. Choroidal images were obtained from swept-source optical coherence tomography (SS-OCT), and the images were processed with a deep learning-based automatic segmentation algorithm and the Niblack auto-local threshold algorithm. Results DCA was detected in 247 eyes (17.4%). In comparison to eyes with C0, those with C2 exhibited significant reductions in choroidal thickness (ChT), luminal area (LA), and stromal area (SA) across all evaluated regions (all P

Abstract Background Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism. Methods We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. Results In this study, we found that extremely low concentrations of GNE-987(2–10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development. Conclusions This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS.

Purpose: To analyze the characteristics of optical coherence tomography in acute macular neuroretinopathy (AMN) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and discuss the prognostic predictors. Methods: Patients with AMN following SARS-CoV-2 infection were divided into two groups according to the presence or absence of hyperreflective outer nuclear layer (ONL) lesion involving the fovea. Results: The first visit included 14 eyes in the fovea-involved group and 20 eyes in the no fovea-involved group. Ellipsoid zone (EZ) hyporeflection and interdigitation zone (IZ) interruption were detected in all eyes. Other common manifestations were myoid zone (MZ) hyperreflection (76.5%), ONL hyperreflection (73.5%), outer plexiform layer (OPL) thickening (64.7%), and EZ interruption (50%). The follow-up period was 48.4 ± 55.3 days. At the last visit, 12 eyes were in the fovea-involved group and 13 eyes in the no fovea-involved group. IZ interruption was detected in all eyes. Other common manifestations were EZ hyporeflection (92.0%), ONL atrophy (40.0%), OPL thickening (36.0%), OPL linear (32.0%), and MZ hyperreflection (32%). The improvement of visual acuity (VA) was -0.5 ± 0.5 and -0.2 ± 0.4 in the fovea-involved group and the no fovea-involved group, respectively, with a statistically significant difference between them (P = 0.045). Initial VA, initial cotton wool spot, initial ONL cyst, final ONL cyst, and final OPL linear were associated with final VA (P = 0.000, P = 0.029, P = 0.044, P = 0.049, P = 0.049, respectively). Conclusions: In the early stage of AMN following SARS-CoV-2 infection, IZ interruption and EZ hyporeflection were the most common manifestations, and pathology of IZ was more serious than that of EZ. Subsequently, OPL and ONL atrophied, and ONL atrophied faster. Regardless of whether hyperreflective ONL involved the fovea, VA improved, with a more noticeable improvement found in the fovea-involved group. The presence of initial ONL cyst and initial cotton wool spot, rapid atrophy of OPL, and poorer initial VA indicating poorer VA outcome.

Abstract Background As multimorbidity becomes common that imposes a considerable burden to patients, but the extent to which widely-used multimorbidity indexes can be applied to quantify disease burden using primary care data in China is not clear. We applied the Chinese Multimorbidity-Weighted Index (CMWI) to health check-ups data routinely collected among older adults by primary care, to examine its validity in measuring multimorbidity associated risks of disability and mortality in annual follow-ups. Methods The study utilized data from annual health check-ups of older adults, which included information on individual age, sex, and 14 health conditions at primary care in a district of Guangzhou, Guangdong, China. The risk of CMWI for mortality was analysed in a total sample of 45,009 persons 65 years and older between 2014 and 2020 (average 2.70-year follow-up), and the risk for disability was in a subsample of 18,320 older adults free of physical impairment in 2019 and followed-up in 2020. Risk of death and disability were assessed with Cox proportional hazard regression and binary logistic regression, respectively, with both models adjusted for age and sex variables. The model fit was assessed by the Akaike information criterion (AIC), and C-statistic or the area under the receiver operating characteristic curve (AUC). Results One unit increase in baseline-CMWI (Median= 1.70, IQR: 1.30-3.00) was associated with higher risk in subsequent disability (OR = 1.12, 95%CI = 1.05,1.20) and mortality (OR = 1.18, 95%CI = 1.14, 1.22). Participants in the top tertile of CMWI had 99% and 152% increased risks of disability and mortality than their counterparts in the bottom tertile. Model fit was satisfied with adequate AUC (0.84) or C-statistic (0.76) for both outcomes. Conclusions CMWI, calculated based on primary care’s routine health check-ups data, provides valid estimates of disability and mortality risks in older adults. This validated tool can be used to quantity and monitor older patients’ health risks in primary care.

Abstract Objectives To establish an MRI-based radiomics model for predicting the microvascular invasion (MVI) status of cHCC-CCA and to investigate biological processes underlying the radiomics model. Methods The study consisted of a retrospective dataset (82 in the training set, 36 in the validation set) and a prospective dataset (25 patients in the test set) from two hospitals. Based on the training set, logistic regression analyses were employed to develop the clinical-imaging model, while radiomic features were extracted to construct a radiomics model. The diagnosis performance was further validated in the validation and test sets. Prognostic aspects of the radiomics model were investigated using the Kaplan–Meier method and log-rank test. Differential gene expression analysis and gene ontology (GO) analysis were conducted to explore biological processes underlying the radiomics model based on RNA sequencing data. Results One hundred forty-three patients (mean age, 56.4 ± 10.5; 114 men) were enrolled, in which 73 (51.0%) were confirmed as MVI-positive. The radiomics model exhibited good performance in predicting MVI status, with the area under the curve of 0.935, 0.873, and 0.779 in training, validation, and test sets, respectively. Overall survival (OS) was significantly different between the predicted MVI-negative and MVI-positive groups (median OS: 25 vs 18 months, p = 0.008). Radiogenomic analysis revealed associations between the radiomics model and biological processes involved in regulating the immune response. Conclusion A robust MRI-based radiomics model was established for predicting MVI status in cHCC-CCA, in which potential prognostic value and underlying biological processes that regulate immune response were demonstrated. Critical relevance statement MVI is a significant manifestation of tumor invasiveness, and the MR-based radiomics model established in our study will facilitate risk stratification. Furthermore, underlying biological processes demonstrated in the radiomics model will offer valuable insights for guiding immunotherapy strategies. Key Points MVI is of prognostic significance in cHCC-CCA, but lacks reliable preoperative assessment. The MRI-based radiomics model predicts MVI status effectively in cHCC-CCA. The MRI-based radiomics model demonstrated prognostic value and underlying biological processes. The radiomics model could guide immunotherapy and risk stratification in cHCC-CCA. Graphical Abstract

Abstract Background Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host’s response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown. Methods A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA). Results IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1β). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner. Conclusion Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.

Abstract Background COVID-19-associated pulmonary fibrosis remains frequent. This study aimed to investigate pulmonary redox balance in COVID-19 ARDS patients and possible relationship with pulmonary fibrosis and long-term lung abnormalities. Methods Baseline data, chest CT fibrosis scores, N-terminal peptide of alveolar collagen III (NT-PCP-III), transforming growth factor (TGF)-β1, superoxide dismutase (SOD), reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) were first collected and compared between SARS-CoV-2 RNA positive patients with moderate to severe ARDS (n = 65, COVID-19 ARDS) and SARS-CoV-2 RNA negative non-ARDS patients requiring mechanical ventilation (n = 63, non-ARDS). Then, correlations between fibroproliferative (NT-PCP-III and TGF-β1) and redox markers were analyzed within COVID-19 ARDS group, and comparisons between survivor and non-survivor subgroups were performed. Finally, follow-up of COVID-19 ARDS survivors was performed to analyze the relationship between pulmonary abnormalities, fibroproliferative and redox markers 3 months after discharge. Results Compared with non-ARDS group, COVID-19 ARDS group had significantly elevated chest CT fibrosis scores (p

Abstract Recent methods of learning latent representations in Domain Adaptation (DA) often entangle the learning of features and exploration of latent space into a unified process. However, these methods can cause a false alignment problem and do not generalise well to the alignment of distributions with large discrepancy. In this study, the authors propose to explore a robust subspace for Semi‐Supervised Domain Adaptation (SSDA) explicitly. To be concrete, for disentangling the intricate relationship between feature learning and subspace exploration, the authors iterate and optimise them in two steps: in the first step, the authors aim to learn well‐clustered latent representations by aggregating the target feature around the estimated class‐wise prototypes; in the second step, the authors adaptively explore a subspace of an autoencoder for robust SSDA. Specially, a novel denoising strategy via class‐agnostic disturbance to improve the discriminative ability of subspace is adopted. Extensive experiments on publicly available datasets verify the promising and competitive performance of our approach against state‐of‐the‐art methods.

Abstract Background BAHD acyltransferases are among the largest metabolic protein domain families in the genomes of terrestrial plants and play important roles in plant growth and development, aroma formation, and biotic and abiotic stress responses. Little is known about the BAHDs in the tea plant, a cash crop rich in secondary metabolites. Results In this study, 112 BAHD genes (CsBAHD01-CsBAHD112) were identified from the tea plant genome, with 85% (98/112) unevenly distributed across the 15 chromosomes. The number of BAHD gene family members has significantly expanded from wild tea plants to the assamica type to the sinensis type. Phylogenetic analysis showed that they could be classified into seven subgroups. Promoter cis-acting element analysis revealed that they contain a large number of light, phytohormones, and stress-responsive elements. Many members displayed tissue-specific expression patterns. CsBAHD05 was expressed at more than 500-fold higher levels in purple tea leaves than in green tea leaves. The genes exhibiting the most significant response to MeJA treatment and feeding by herbivorous pests were primarily concentrated in subgroups 5 and 6. The expression of 23 members of these two subgroups at different time points after feeding by tea green leafhoppers and tea geometrids was examined via qPCR, and the results revealed that the expression of CsBAHD93, CsBAHD94 and CsBAHD95 was significantly induced after the tea plants were subjected to feeding by both pricking and chewing pests. Moreover, based on the transcriptome data for tea plants being fed on by these two pests, a transcriptional regulatory network of different transcription factor genes coexpressed with these 23 members was constructed. Conclusions Our study provides new insights into the role of BAHDs in the defense response of tea plants, and will facilitate in-depth studies of the molecular function of BAHDs in resistance to herbivorous pests.

Summary: Mesoscale to nanoscale three-dimensional (3D) fabrication mostly requires complicated industry processing techniques. Here, we present a protocol for 3D shaping control by solidifying a water-based TiO2 nanofluid drop on a polygonal wettability-patterned surface. We detail the steps for preparing stable TiO2 nanofluid and wettability-patterned surfaces. We then describe the experimental procedure to obtain various and precise 3D morphologies by adjusting the deposited TiO2 nanofluid drop volume. This protocol provides a promising technique for future 3D manufacturing.For complete details on the use and execution of this protocol, please refer to Jiang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background: Myokines play vital roles in both stable coronary artery disease (SCAD) and depression. Meanwhile, there is a pressing necessity to find effective biomarkers for early predictor of major adverse cardiovascular events (MACE) in SCAD patients with depressive symptoms. Methods: A single-center, 5-year follow-up study was investigated. MACE was defined as composite end points, including cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, coronary artery revascularization, or hospitalization for unstable angina. Results: A total of 116 SCAD patients were enrolled, consisting of 30 cases (25.9%) without depressive symptoms and 86 cases (74.1%) with depressive symptoms. During the follow-up, 3 patients (2.6%) were lost. Out of 113 patients, 51 (45.1%) experienced MACE. In the subgroup of 84 SCAD patients with depressive symptoms, 44 cases (52.4%) of MACE were observed. Finally, mature brain-derived neurotrophic factor (mBDNF), pro-brain-derived neurotrophic factor, receptor activator of nuclear factor-κB ligand, smoking history, hypertension and cystatin C were incorporated into the predictive model. Conclusions: Depressive symptoms represent an independent risk factor for MACE in patients with SCAD. Additionally, low mBDNF expression may be an important early predictor for MACE in SCAD patients with depressive symptoms. The predictive model may exhibit a commendable predictive performance for MACE in SCAD patients with depressive symptoms.

Objective: Based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, we analyzed the signals of potential adverse events (AEs) of orlistat in the real world to provide a reference for its safe clinical use. Methods: The FAERS database and OpenVigil 2.1 were used to obtain data on adverse events of orlistat from the first quarter of 2004 to the first quarter of 2023, and to analyze the population in which the adverse events occurred. And the signals of their potential adverse events were mined using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and empirical Bayesian geometric mean (EBGM). Result: A total of 21,079 reports of adverse events with orlistat as the primary suspected drug were collected in this study. Using four disproportionate analyses, we screened 117 preferred terms (PTs) involving 18 system organ classes (SOCs). We found that the most common adverse events at SOC level for orlistat remained ''gastrointestinal disorders'', while ''metabolism and nutrition disorders'', ''renal and urinary disorders'', ''musculoskeletal and connective tissue disorders'' and ''hepatobiliary disorders'' also ranked high in the number of case reports. In addition, at the PT level, we identified several new signals of adverse events not mentioned in the specification, including ''lipiduria'', ''anal haemorrhage'', ''rectal haemorrhage'', ''haematochezia'', ''sigmoiditis'', ''diverticulitis'' and ''muscle spasms''. Conclusion: Most of the adverse events found in this study are consistent with the results described in the drug label. At the same time, we also found some new adverse events, which require more prospective studies to verify and elucidate their relationship with orlistat.

Food is vital to the people, and safety comes first in food. Food safety is crucial to people's livelihood, economic development, and social stability. It represents people's aspiration for a better life and grabs great public attention. In recent years, while China has achieved significant progress in food safety, the situation remains severe, with incidents such as excessive residues of agricultural and veterinary drugs, as well as illegal addition of toxic and harmful substances. As an important technical support for ensuring food safety, food safety inspection and testing institutions also exhibit a mixed bag of performance. Problems such as inadequate personnel management, improper use of facilities and equipment, weak legal awareness resulting in issuance of false reports have frequently occurred, seriously disrupting the normal order of the inspection and testing market and affecting the authority and accuracy of food safety testing. Based on the capacity verification of inspection and testing organizations in Zhejiang Province in recent years, this paper studies the typical problems faced by food inspection and testing institutions in terms of management level and testing capabilities, analyzes the root causes in depth, and proposes specific strategies from three aspects: Strengthening the main responsibility of inspection and testing institutions, combining regulatory departments with supervision and guidance, and enhancing industry self-discipline, aiming to continuously improve their inspection and testing capabilities, promote the high-quality development of food inspection and testing institutions, and effectively ensure the safety of every bite of food.

Abstract Background Glioblastoma (GBM) is a relatively prevalent primary tumor of the central nervous system in children, characterized by its high malignancy and mortality rates, along with the intricate challenges of achieving complete surgical resection. Recently, an increasing number of studies have focused on the crucial role of super-enhancers (SEs) in the occurrence and development of GBM. This study embarks on the task of evaluating the effectiveness of MZ1, an inhibitor of BRD4 meticulously designed to specifically target SEs, within the intricate framework of GBM. Methods The clinical data of GBM patients was sourced from the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the gene expression data of tumor cell lines was derived from the Cancer Cell Line Encyclopedia (CCLE). The impact of MZ1 on GBM was assessed through CCK-8, colony formation assays, EdU incorporation analysis, flow cytometry, and xenograft mouse models. The underlying mechanism was investigated through RNA-seq and ChIP-seq analyses. Results In this investigation, we made a noteworthy observation that MZ1 exhibited a substantial reduction in the proliferation of GBM cells by effectively degrading BRD4. Additionally, MZ1 displayed a notable capability in inducing significant cell cycle arrest and apoptosis in GBM cells. These findings were in line with our in vitro outcomes. Notably, MZ1 administration resulted in a remarkable decrease in tumor size within the xenograft model with diminished toxicity. Furthermore, on a mechanistic level, the administration of MZ1 resulted in a significant suppression of pivotal genes closely associated with cell cycle regulation and epithelial-mesenchymal transition (EMT). Interestingly, our analysis of RNA-seq and ChIP-seq data unveiled the discovery of a novel prospective oncogene, SDC1, which assumed a pivotal role in the tumorigenesis and progression of GBM. Conclusion In summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.

Abstract Rockbursts are a complex phenomenon characterized by a violent ejection of rock fragments from the free face of deep underground mines. Due to the sudden, disruptive, and complex nature of these events, accurate predictions of rockbursts are difficult. Therefore, geotechnical intervention is imperative to prevent the occurrence of a rockburst. The scenarios of microwave destressing is introduced here as an application method to potentially prevent their occurrence. To understand the influences of microwave destressing, such as microwave exposure duration, spatial layout, and geometric parameters of the microwave preconditioned zone (MPZ), on the occurrence of a rockburst, numerical simulation was conducted based on an impact-induced rockburst model. The feasibility of microwave destressing technology was validated numerically. This paper also provides guidance for the utilization of microwave destressing in practice. Discontinuous MPZ is suitable for a known blasting source with a fixed position, and continuous MPZ can be applied for a working condition with multiple blasting sources with variable positions. A closer distance of MPZ from the free face results in a better microwave destressing effect. However, the closer distance of MPZ from the free face also introduces more negative influences on the static stability of surrounding rock.

Abstract As an emerging business model, merchants are selling surplus food in blind boxes, which provides new opportunities for reducing waste and promoting sustainable development. Surplus food blind boxes, however, have not been extensively researched in terms of design and marketing strategies. Therefore, we are examining how to increase consumers’ purchase intention regarding surplus food blind boxes as well as the relationship between purchase intention, continuous intention, and recommendation intention. In this paper, two studies are conducted. As part of study 1, We used factor analysis to explore the reasons that influence consumers to purchase. In study 2, we utilized structural equation modeling to examine the impact of purchase intention on continuous intention and recommendation intention. Results indicate that food quality, perceived sustainability, and conspicuous consumption are the most important positive factors. The most important negative factors are perceived food risk, resistance to sales techniques, taste anxiety, and inadequate marketing strategies. Based on our findings, we constructed a path relationship between purchase intention, continuous intention, and recommendation intention. The purchase intention of the surplus food blind box users directly influences the recommendation intention and the continuous intention, while the recommendation intention indirectly influences the continuous intention. This study did not demonstrate that gender had a moderating effect. Meanwhile, it provides a reference for the actual marketing management of surplus food blind box merchants.

High-quality images are of great significance for vision tasks in underwater environments. However, as light propagates through water, it is scattered and absorbed, which commonly causes issues like color distortion and loss of detail, making the capture of high-quality images challenging. To improve the quality of underwater images, we propose an underwater image enhancement method that is based on channel similarity to adaptive color correction and stationary wavelet detail enhancement. Specifically, We first innovatively introduce channel similarity values to avoid red artifacts during color correction, and finely adjust the compensation amount at the pixel level based on the intensity difference between the red and green channels. By designing a new dynamic normalization range based on channel similarity, our color correction method adaptively adjusts the dynamic range of each RGB channel’s pixel value. This accommodation for color deviations in various underwater scenes enhances the color saturation of images. Subsequently, using the stationary wavelet transform, we accurately decompose the image into low-frequency and high-frequency components. Through fine processing of the low-frequency components, we optimize detail performance and enhance the visual clarity of the underwater scene. Extensive experiments on four benchmark datasets validate that our method is state-of-the-art in underwater image enhancement, excelling in both qualitative and quantitative evaluations. Additionally, our method bolsters the precision of tasks such as keypoint matching and edge detection within the realm of image processing. The code is available at https://github.com/Zhenbo-Wang/Adaptive-Color-Correction-and-Stationary-Wavelet-Detail-Enhancement.

Land cover classification has the goal to attribute each pixel of high-resolution remoste sensing image with planimetric category labels (such as vegetation, building, and water). In recent years, many serial deep-learning architectures (features are delivered through a single path, such as in ResNet, MobileNet, and Segformer) based on convolutional neural networks and attention mechanisms have been widely explored in land cover classification. However, high-resolution remote sensing images typically have abundant textual details, variable scales in objects, large intraclass variance, and similar interclass correlation, which bring challenges to land cover classification. In this work, we present two pluggable modules to further boost serial learning architecture: first, to cope with ambiguous boundaries caused by lost details and fragmented segmentation stemmed from scale variances, a combination of spatial attention and channel attention is proposed for multiscale feature reconstruction (MSFR); second, to mitigate the classification error caused by intraclass variance and interclass correlation, we explore an interclass attention weighting (ICAW) module, which builds feature vectors for each category, and applies a multihead attention model to capture self-attention dependence among different categories. The experimental results demonstrate that the proposed modules are feasible to the existing serial learning architectures and can improve overall accuracy (OA) by 5.64% on the ISPRS Vaihingen two-dimensional dataset (using ResNet50 as a backbone); in particular, the OA values are 80.68% and 86.32% before and after using the proposed modules, respectively. In addition, compared with other state-of-the-art models, our method can achieve similar or even better classification results, yet offer superior inference performance.

In this study, the metabolic profiles of traditional craftsmanship (TC) Liupao tea presented great changes at different processing stages. The contents of flavonoids and their glycosides generally exhibited a continuing downward trend, resulting in the sensory quality of TC-Liupao tea gradually improved. However, the taste of TC-Liupao tea faded when piling exceeded 12 h, as a result of the excessive degradation of some key flavor substances. Therefore, it could be deduced that piling for 10 h might be optimum for the quality formation of TC-Liupao tea. Sphingomonas, Acrobacter, Microbacterium, and Methylobacterium were the dominant bacteria during piling. The correlation analysis between differential metabolites and bacteria showed that only Sphingomonas and Massilia were significantly correlated to metabolites, demonstrating that the bacteria had less effect on the transformation of metabolites. Thus, the metabolic structure change during the process of TC-Liupao tea might be mainly attributed to the high temperature and humidity environment.

BackgroundsType 2 Diabetes Mellitus (T2DM) has become a significant global public health issue, characterized by a rising prevalence and associated deficits across multiple organ systems. Our study aims to utilize the DTI-ALPS technique to assess the change of ALPS index in T2DM patients, and to explore whether such changes are correlated with cognition level and diffusion parameters.MethodsThe study involved 41 patients with T2DM (mean age, 60.49 ± 8.88 years) and 27 healthy controls (mean age, 58.00 ± 7.63 years). All subjects underwent MRI examination, cognitive assessment, and laboratory tests. Tract-based spatial statistics (TBSS) was used to evaluate white matter changes. GLM was performed to check the DTI-ALPS index difference between T2DM and HC groups. Spearman correlation analysis and partial correlation analysis were used to analyze the correlation between the DTI-ALPS index and diffusion properties & cognitive scores.ResultsThe results show that the ALPS index was lower in T2DM patients. MoCA score was significantly correlated with the ALPS index. Patients with T2DM had a significant increase in both mean diffusivity (MD) and radial diffusivity (RD) and decrease in fractional anisotropy (FA) compared to the HC group.ConclusionThe results suggest that the ALPS index is decreased in T2DM patients and associates with cognitive level.

Gouty stone ulcers inducing bloodstream infections leading to chest wall and mediastinal abscesses and progression to sepsis and hemophagocytic syndrome are extremely rare in clinical practice. Keep in mind the possibility of coexistence of gout and septic arthritis. Prompt and accurate diagnosis and treatment of hemophagocytic syndrome (HPS), a highly fatal disease with acquired immunoregulatory abnormalities and release of large amounts of inflammatory factors, are important to save the patient's life.

The coexistence of chronic pain and depression in clinical practice places a substantial social burden and profoundly impacts in patients. Although a clear correlation exists, the underlying mechanism of comorbidity between chronic pain and depression remains elusive. Research conducted in recent decades has uncovered that soluble epoxide hydrolase, a pivotal enzyme in the metabolism of polyunsaturated fatty acids, plays a crucial role in inflammation. Interestingly, this enzyme is intricately linked to the development of both pain and depression. With this understanding, this review aims to summarize the roles of soluble epoxide hydrolase in pain, depression, and their comorbidity. Simultaneously, we will also explore the underlying mechanisms, providing guidance for future research and drug development.

Abstract The anonymous and tamper‐proof nature of the blockchain poses significant challenges in auditing and regulating the behaviour and data on the chain. Criminal activities and anomalies are frequently changing, and fraudsters are devising new ways to evade detection. Moreover, the high volume and complexity of transactions and asymmetric errors make data classification more challenging. Also, class imbalances and high labelling costs are hindering the development of effective algorithms. In response to these issues, the authors present BlockDetective, a novel framework based on GCN that utilizes student–teacher architecture to detect fraudulent cryptocurrency transactions that are related to money laundering. The authors’ method leverages pre‐training and fine‐tuning, allowing the pre‐trained model (teacher) to adapt better to the new data distribution and enhance the prediction performance while teaching a new, light‐weight model (student) that provides abstract and top‐level information. The authors’ experimental results show that BlockDetective outperforms state‐of‐the‐art research methods by achieving top‐notch performance in detecting fraudulent transactions on the blockchain. This framework can assist regulators and auditors in detecting and preventing fraudulent activities on the blockchain, thereby promoting a more secure and transparent financial system.

AIM: To describe the optical coherence tomography angiography (OCTA) characteristics of exudative and non-exudative treatment-naïve pachychoroid neovasculopathy (PNV). METHODS: Thirty-five patients with exudative treatment-naïve PNV and 13 with non-exudative treatment-naïve PNV between March 2020 and December 2021 were included. All patients underwent ophthalmologic examination, including fluorescein angiography (FA), indocyanine green angiography (ICGA), spectral-domain OCT, and OCTA. The clinical data of the patients were retrospectively analyzed. RESULTS: The study included 51 eyes from 46 patients, of whom 33 (71.7%) were male. The central macular thickness (CMT) in the exudative PNV group was significantly higher than that in the non-exudative PNV group (383.97±132.16 µm vs 213.13±51.63 µm; P

Abstract Multiple myeloma (MM) is related to immune disorders, recent studys have revealed that immunotherapy can greatly benefit MM patients. Immune checkpoints can negatively modulate the immune system and are closely associated with immune escape. Immune checkpoint-related therapy has attracted much attention and research in MM. However, the efficacy of those therapies need further improvements. There need more thoughts about the immune checkpoint to translate their use in clinical work. In our review, we aggregated the currently known immune checkpoints and their corresponding ligands, further more we propose various ways of potential translation applying treatment based on immune checkpoints for MM patients.

Abstract Objectives To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial detachment (PED). Methods Systematic review identifying studies comparing intravitreal ranibizumab (IVR), intravitreal aflibercept (IVA) and intravitreal conbercept (IVC) published before Mar 2022. Results One randomized controlled trial and 6 observational studies were selected for meta-analysis (1,069 patients). The change of best corrected visual acuity (BCVA) in IVA 2.0 mg group was better than IVR 0.5 mg (average difference 0.07) and IVR 2.0 mg (average difference 0.10), the differences were statistically significant. The change of the height of PED in IVA 2.0 group was better than IVR 0.5 group (average difference 45.30), the difference was statistically significant. The proportion of patients without PED at last visit in IVA 2.0 group were better than those in IVR 2.0 group (hazard ratio 1.91), the difference was statistically significant. There was no significant difference compared with IVR 0.5 group (hazard ratio 1.45). IVA required fewer injections than IVR, with a mean difference of -1.58. Conclusions IVA appears to be superior to IVR in improvement of BCVA, height decrease of PED and regression of PED with less injections in nAMD with PED.

Abstract Background Echinococcus granulosus can manipulate its host's immune response to ensure its own survival. However, the effect of histone modifications on the regulation of the NOD-like receptor protein 3 (NLRP3) inflammasome and downstream interleukin-1β (IL-1β) production in response to the parasite is not fully understood. Methods We evaluated IL-1β secretion through enzyme-linked immunosorbent assay and assessed reactive oxygen species levels using the dichlorodihydrofluorescein diacetate probe. Western blotting and quantitative real-time polymerase chain reaction were performed to examine the expression of NLRP3 and IL-1β in mouse peritoneal macrophages and Tohoku Hospital Pediatrics-1 cells, a human macrophage cell line. The presence of trimethylated histone H3 lysine 27 (H3K27me3) modification on NLRP3 and IL-1β promoters was studied by chromatin immunoprecipitation. Results Treatment with E. granulosus cyst fluid (EgCF) considerably reduced IL-1β secretion in mouse and human macrophages, although reactive oxygen species production increased. EgCF also suppressed the expression of NLRP3 and IL-1β. Mechanistically, EgCF prompted the enrichment of repressive H3K27me3 modification on the promoters of both NLRP3 and IL-1β in macrophages. Notably, the presence of EgCF led to a significant reduction in the expression of the H3K27me3 demethylase KDM6B. Conclusions Our study revealed that EgCF inhibits KDM6B expression and H3K27me3 demethylation, resulting in the transcriptional inhibition of NLRP3 and IL-1β. These results provide new insights into the immune evasion mechanisms of E. granulosus. Graphical Abstract

Abstract Objective To evaluate the image quality of reduced field-of-view (rFOV) DWI for abdominal imaging at 5.0 Tesla (T) compared with 3.0 T. Methods Fifteen volunteers were included into this prospective study. All the subjects underwent the 3.0 T and 5.0 T MR examinations (time interval: 2 ± 1.9 days). Free-breathing (FB), respiratory-triggered (RT), and navigator-triggered (NT) spin-echo echo-planner imaging-based rFOV-DWI examinations were conducted at 3.0 T and 5.0 T (FB3.0 T, NT3.0 T, RT3.0 T, FB5.0 T, NT5.0 T, and RT5.0 T) with two b values (b = 0 and 800 s/mm2), respectively. The signal-to-noise ratio (SNR) of different acquisition approaches were determined and statistically compared. The image quality was assessed and statistically compared with a 5-point scoring system. Results The SNRs of any 5.0 T DWI images were significantly higher than those of any 3.0 T DWI images for same anatomic locations. Moreover, 5.0 T rFOV-DWIs had the significantly higher sharpness scores than 3.0 T rFOV-DWIs. Similar distortion scores were observed at both 3.0 T and 5.0 T. Finally, RT5.0 T displayed the best overall image quality followed by NT5.0 T, FB5.0 T, RT3.0 T, NT3.0 T and FB3.0 T (RT5.0 T = 3.9 ± 0.3, NT5.0 T = 3.8 ± 0.3, FB5.0 T = 3.4 ± 0.3, RT3.0 T = 3.2 ± 0.4, NT3.0 T = 3.1 ± 0.4, and FB3.0 T = 2.7 ± 0.4, p

Abstract Background and aims The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI+ HCC and investigate the underlying immune infiltration patterns with radiomics features. Methods Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI+ HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE+ macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO. Results Elevated levels of APOE+ macrophages and iCAFs were detected in MVI+ HCC. There was a strong correlation between the infiltration of APOE+ macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE+ macrophages. APOE+ macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE+ macrophages and iCAFs. Conclusion This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI+ HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE+ macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI+ HCC.

Abstract The clinical benefit of tyrosine kinase inhibitors (TKIs)-based systemic therapy for advanced hepatocellular carcinoma (HCC) is limited due to drug resistance. Here, we uncover that lipid metabolism reprogramming mediated by unconventional prefoldin RPB5 interactor (URI) endows HCC with resistance to TKIs-induced ferroptosis. Mechanistically, URI directly interacts with TRIM28 and promotes p53 ubiquitination and degradation in a TRIM28-MDM2 dependent manner. Importantly, p53 binds to the promoter of stearoyl-CoA desaturase 1 (SCD1) and represses its transcription. High expression of URI is correlated with high level of SCD1 and their synergetic expression predicts poor prognosis and TKIs resistance in HCC. The combination of SCD1 inhibitor aramchol and deuterated sorafenib derivative donafenib displays promising anti-tumor effects in p53-wild type HCC patient-derived organoids and xenografted tumors. This combination therapy has potential clinical benefits for the patients with advanced HCC who have wild-type p53 and high levels of URI/SCD1.

There is limited research on robotic systems designed for Endoscopic Retrograde Cholangiopancreatography (ERCP) procedures using a side-view duodenoscope. The unique structure of the duodenoscope presents challenges to safely and precisely control the distal end pose. Control methods applied can reduce potential medical risks. We have redesigned the control section of the duodenoscope to facilitate its manipulation by a robotic system. An orthogonal compensator is employed to rectify the motion planes to standard planes. A hysteresis compensator based on the Prandtl-Ishlinskii model enables precise control of the distal pose of the duodenoscope. Furthermore, we utilize a contact force prediction model to prevent excessive contact force at the distal end. The performance of the modified duodenoscope is comparable to that of the standard duodenoscope. Following orthogonal compensation, the deviation angles of the motion planes is reduced by 32% to 98%. Post-hysteresis compensation, the root mean square error (RMSE) of the output angle of the distal end is decreased from 8.347° to 4.826°. The accuracy of distal end contact force prediction was approximately ±25% under conditions of high contact force. In conclusion, the modification and control strategy we proposed can achieve relatively safe and precise control of bending section, laying the foundation for the subsequent roboticization of duodenoscope systems for ERCP procedures.

This study focuses on the synthesis, fabrication, and characterization of a molecularly imprinted polymer (MIP) sensor tailored for the selective determination of 4,4′-oxydianiline (4,4′-ODA) in plastic products. Notably, by integrating the sensor matrix with pyrolyzed copper/carbon material derived from Cu-BTC MOF, a remarkable enhancement in electrochemical performance is achieved. The Cu-BTC material is grown successfully on the surface of carbon nanotubes (CNTs) and subjected to calcination at 800 °C, yielding a CNT/Cu/C composite. This composite exhibits an increased surface area and enhanced electron transfer capability, resulting in an improved current response. To augment the selective detection capability of the modified electrodes for 4,4′-ODA, molecularly imprinted polymers (MIPs) were incorporated onto the composite surface. The modified electrode (CNT-2/Cu/C/MIP/GCE) was synthesized using acrylamide (AM) and methacrylic acid (MAA) as dual-functional monomers with 4,4′-ODA as a template molecule via precipitation polymerization. The differential pulse voltammetric (DPV) current response to 4,4′-ODA showed a favorable linear relationship within the concentration range of (0.15–10 μM,10–100 μM), with a detection limit of 0.05 μM. Moreover, the CNT-2/Cu/C/MIP/GCE sensor demonstrates exceptional sensitivity, specificity, consistency, and durability. Furthermore, this approach has proven effective in detecting 4,4′-ODA in spiked nylon spatula samples, with recovery rates ranging from 86.3% to 103.5%.

BackgroundAlzheimer’s disease (AD) is an age-related neurodegenerative disorder with no effective interventions for curing or modifying its progression. However, emerging research suggests that vitamin A in the diet may play a role in both the prevention and treatment of AD, although the exact mechanisms are not fully understood.ObjectivesThis study aims to investigate the dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aβ pathology shedding light on its potential as a dietary intervention for AD prevention and treatment.MethodsThe APP/PS1-AD mouse model was employed and divided into three dietary groups: vitamin A-deficient (VAD), normal vitamin A (VAN), and vitamin A-supplemented (VAS) for a 12-week study. Neurobehavioral functions were assessed using the Morris Water Maze Test (MWM). Enzyme-linked immunosorbent assay (ELISA) was used to quantify levels of Diamine Oxidase (DAO), D-lactate, IL-6, IL-1β, and TNF-a cytokines. Serum vitamin A levels were analyzed via LC-MS/MS analysis. Immunohistochemical analysis and morphometry were performed to evaluate the deposition of Aβ in brain tissue. The gut microbiota of APP/PS1 mice was analyzed using 16S rRNA sequencing analysis. Additionally, transcriptomic analysis was conducted on intestinal tissue from APP/PS1 mice.ResultsNo significant changes in food intake and body weight were observed among the groups. However, the VAD and VAS groups showed reduced food intake compared to the VAN group at various time points. In terms of cognitive function, the VAN group performed better in the Morris Water Maze Test, indicating superior learning and memory abilities. The VAD and VAS groups exhibited impaired performance, with the VAS group performing relatively better than the VAD group. Serum vitamin A concentrations differed significantly among the groups, with the VAS group having the highest concentration. Aβ levels were significantly higher in the VAD group compared to both the VAN and VAS groups. Microbial analysis revealed that the VAS and VAN groups had higher microbial diversity than the VAD group, with specific taxa characterizing each group. The VAN group was characterized by taxa such as Actinohacteriota and Desulfovibrionaceae, while the VAD group was characterized by Parabacteroides and Tannerellaceae. The VAS group showed similarities with both VAN and VAD groups, with taxa like Desulfobacterota and Desulfovibrionaceae being present. The VAD vs. VAS, VAD vs. VAN, and VAS vs. VAN comparisons identified 571, 313, and 243 differentially expressed genes, respectively, which associated with cellular and metabolic processes, and pathway analysis revealed enrichment in pathways related to chemical carcinogenesis, drug metabolism, glutathione metabolism, and immune-related processes. The VAD group exhibited higher levels of D-lactate, diamine oxidase, and inflammatory cytokines (TNF-a, IL-1β, IL-6) compared to the VAN and VAS groups.ConclusionDietary vitamin A supplementation modulates the gut microbiota, intestinal permeability, inflammatory factors, and Aβ protein formation, offering insights into the pathogenesis of AD and potential therapeutic avenues for further exploration. This research highlights the intricate interplay between diet, gut microbiota, and neurodegenerative processes, emphasizing the importance of dietary interventions in managing AD-related pathologies.

Social dominance is a universal phenomenon among grouped animals that profoundly affects survival, health, and reproductive success by determining access to resources, and exerting a powerful influence on subsequent behavior. However, the understanding of pain and anxiety comorbidities in dominant or subordinate animals suffering from chronic pain is not well-defined. Here, we provide evidence that subordinate mice are more susceptible to pain-induced anxiety compared to dominant mice. We propose that the gut microbiota may play a mediating role in this mechanism. Our findings demonstrate that transplantation of fecal microbiota from subordinate mice with chronic inflammatory pain, but not dominant mice, into antibiotics-treated pseudo-germ-free mice significantly amplifies anxiety-like phenotypes, highlighting the critical involvement of gut microbiota in this behavioral response. Using chronic inflammatory pain model, we carried out 16S rRNA sequencing and untargeted metabolomic analyses to explore the relationship between microbiota and metabolites in a stable social hierarchy of mice. Interestingly, anxiety-like behaviors were directly associated with some microbial genera and metabolites, especially bile acid metabolism. Overall, we have demonstrated a close relationship between social status and anxiety susceptibility, highlighting the contributions of gut microbiota and the associated metabolites in the high-anxiety state of subordinate mice with chronic inflammatory pain.

Objectives: To evaluate radiation exposure, image quality, and diagnostic performance of coronary CT angiography (CCTA) using the invasive coronary angiography (ICA) as the reference standard in patients with irregular heart rhythm on a 0.25 s rotation time, 16 cm coverage, single-beat, CT scanner with AI-assisted motion correction. Methods: CCTA data-sheets of 427 patients using a CT scanner with an ECG monitoring system and motion correction algorithm were collected retrospectively. All the patients were divided into two groups: regular heart rhythm (357 patients) and irregular heart rhythm (70 patients). 22 patients in irregular heart rhythm underwent ICA. Image quality and effective dose in both groups were evaluated and compared. Image quality was evaluated on 5-point scales. The diagnostic performance of CCTA in irregular heart rhythm group was compared with the results of ICA. Results: The image quality in both groups was similar (4.34 ± 0.47 vs 4.37 ± 0.48, p > 0.05). No significant difference was observed in effective dose between two groups (2.7 ± 0.7 vs 2.9 ± 1.3, p > 0.05). The diagnostic accuracy was 90.91% in a patient-based analysis, 96.97% in a vessel-based analysis, and 98.61% in a segment-based analysis. In irregular heart rhythm group, gender was an important factor affecting the number of CCTA scans in a single examination and the radiation dose exposed to the patient. Conclusions: For patients with irregular heart rhythm, a CT scanner with an ECG monitoring system and motion correction algorithm can not only reduce the radiation dose to the same level as patients with normal heart rhythms, but also ensure that the images with high diagnostic accuracy.

As an important measure to achieve high-quality economic development in China, the implementation of low-carbon city pilot policy (LCCP) will inevitably have an impact on enterprises’ environmental protection behavior, but the empirical evidence in this field is limited. Therefore, based on the data of Chinese A-share listed industrial enterprises in Shanghai and Shenzhen from 2008 to 2020, this paper empirically tests the impact of LCCP on corporate environmental performance (EP) and its mechanism of action by using the multiperiod difference-in-difference (DID) method. The results show that (1) the implementation of LCCP has significantly improved EP, and after a series of necessary tests such as parallel trend and placebo, the conclusion remains robust. (2) LCCP promotes enterprises to improve their EP mainly through the pressure of environmental supervision, financing constraints, and market competition. (3) The policy effect of LCCP varies with the nature of enterprise property rights, pollution attributes, and technical level. State-owned enterprises, heavily polluting enterprises, and high-tech enterprises respond more positively to LCCP, and the effect of EP improvement affected by the policy is more obvious. Further analysis shows that facing the pressure of environmental policy, state-owned enterprises mainly deal with it through two methods: increasing environmental protection investment and strengthening green innovation; heavy-polluting enterprises tend to increase investment in environmental protection; high-tech enterprises mainly benefit from the improvement of the green innovation level. Our findings have important policy implications for improving LCCP to achieve high-quality economic development based on the improvement of EP.

Background: Single-cell sequencing (SCS) is a technique used to analyze the genome, transcriptome, epigenome, and other genetic data at the level of a single cell. The procedure is commonly utilized in multiple fields, including neurobiology, immunology, and microbiology, and has emerged as a key focus of life science research. However, a thorough and impartial analysis of the existing state and trends of SCS-related research is lacking. The current study aimed to map the development trends of studies on SCS during the years 2010–2022 through bibliometric software.Methods: Pertinent papers on SCS from 2010 to 2022 were obtained using the Web of Science Core Collection. Research categories, nations/institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords were analyzed using VOSviewer, the R package “bibliometric”, and CiteSpace.Results: The bibliometric analysis included 9,929 papers published between 2010 and 2022, and showed a consistent increase in the quantity of papers each year. The United States was the source of the highest quantity of articles and citations in this field. The majority of articles were published in the periodical Nature Communications. Butler A was the most frequently quoted author on this topic, and his article “Integrating single-cell transcriptome data across diverse conditions, technologies, and species” has received numerous citations to date. The literature and keyword analysis showed that studies involving single-cell RNA sequencing (scRNA-seq) were prominent in this discipline during the study period.Conclusion: This study utilized bibliometric techniques to visualize research in SCS-related domains, which facilitated the identification of emerging patterns and future directions in the field. Current hot topics in SCS research include COVID-19, tumor microenvironment, scRNA-seq, and neuroscience. Our results are significant for scholars seeking to identify key issues and generate new research ideas.

Pancreatic adenocarcinoma (PAAD) remains challenging to diagnose and treat clinically due to its difficult early diagnosis, low surgical resection rate, and high risk of postoperative recurrence and metastasis. SMAD4 is a classical mutated gene in pancreatic cancer and is lost in up to 60%–90 % of PAAD patients, and its mutation often predicts a poor prognosis and treatment resistance. In this study, based on the expression profile data in The Cancer Genome Atlas database, we identified a ceRNA network composed of 2 lncRNAs, 1 miRNA, and 4 mRNAs through differential expression analysis and survival prognosis analysis. Among them, high expression of KLK10/LIPH/PARD6B/SLC52A3 influenced the prognosis and overall survival of PAAD patients. We confirmed the high expression of these target genes in pancreatic tissue of pancreatic-specific SMAD4-deficient mice. In addition, immune infiltration analysis showed that the high expression of these target genes affects the tumor immune environment and contributes to the progression of PAAD. Abnormal overexpression of these target genes may be caused by hypermethylation. In conclusion, we found that KLK10/LIPH/PARD6B/SLC52A3 is a potential prognostic marker for PAAD based on a competing endogenous RNA-mediated mechanism and revealed the potential pathogenic mechanism by which deficient expression of SMAD4 promotes pancreatic cancer progression, which provides a new pathway and theoretical basis for targeted therapy or improved prognosis of pancreatic cancer. These data will help reveal potential therapeutic targets for pancreatic cancer and improve the prognosis of pancreatic cancer patients.

Abstract Background Echinococcus granulosus cyst fluid (EgCF) weakens macrophage inflammatory responses, thereby enabling the parasite to evade the immune system. However, the role of histone modification in this process remains to be explored. Methods The levels of IL-6, TNF-α, IL-10, H3K4me3, and KDM5B were detected using quantitative real-time PCR, ELISA, and Western blotting. The enrichment of H3K4me3 and KDM5B at the promoter of inflammatory factors was detected by chromatin immunoprecipitation. Results Based on EgCF-stimulated macrophage models, we found that EgCF significantly inhibited mRNA expression and protein secretion of IL-6 and TNF-α and upregulated mRNA expression of IL-10 under the influence of TLR4. EgCF lowered the level of H3K4me3 and promoted the transcription and protein stability of histone demethylase KDM5B. Chromatin immunoprecipitation analysis revealed that EgCF suppressed the enrichment of H3K4me3 modification at the promoters of TNF-α and IL-6 and downregulated their expression in macrophages. Additionally, the inhibition of KDM5B activity by CPI-455 weakened the anti-inflammatory effect of EgCF. Conclusions Our findings demonstrate a novel mechanism through which EgCF promotes KDM5B expression and inhibits the enrichment of H3K4me3 at the promoters of inflammatory cytokines to suppress the inflammatory response. Graphical Abstract

Abstract Background Cancer patients can achieve dramatic responses to chemotherapy yet retain resistant tumor cells, which ultimately results in relapse. Although xenograft model studies have identified several cellular and molecular features that are associated with chemoresistance in acute myeloid leukemia (AML), to what extent AML patients exhibit these properties remains largely unknown. Results We apply single-cell RNA sequencing to paired pre- and post-chemotherapy whole bone marrow samples obtained from 13 pediatric AML patients who had achieved disease remission, and distinguish AML clusters from normal cells based on their unique transcriptomic profiles. Approximately 50% of leukemic stem and progenitor populations actively express leukemia stem cell (LSC) and oxidative phosphorylation (OXPHOS) signatures, respectively. These clusters have a higher chance of tolerating therapy and exhibit an enhanced metabolic program in response to treatment. Interestingly, the transmembrane receptor CD69 is highly expressed in chemoresistant hematopoietic stem cell (HSC)-like populations (named the CD69 + HSC-like subpopulation). Furthermore, overexpression of CD69 results in suppression of the mTOR signaling pathway and promotion of cell quiescence and adhesion in vitro. Finally, the presence of CD69 + HSC-like cells is associated with unfavorable genetic mutations, the persistence of residual tumor cells in chemotherapy, and poor outcomes in independent pediatric and adult public AML cohorts. Conclusions Our analysis reveals leukemia stem cell and OXPHOS as two major chemoresistant features in human AML patients. CD69 may serve as a potential biomarker in defining a subpopulation of chemoresistant leukemia stem cells. These findings have important implications for targeting residual chemo-surviving AML cells.

Abstract Background Pulmonary embolism is a severe cardiovascular disease and can be life-threatening if left untreated. However, the detection rate of pulmonary embolism using existing pretest probability scores remained relatively low and clinical rule out often relied on excessive use of computed tomographic pulmonary angiography. Methods We retrospectively collected data from pulmonary embolism suspected patients in Zhongshan Hospital from July 2018 to October 2022. Pulmonary embolism diagnosis and severity grades were confirmed by computed tomographic pulmonary angiography. Patients were randomly divided into derivation and validation set. To construct the Pulmonary Embolism Comprehensive Screening Score (PECSS), we first screened for candidate clinical predictors using univariate logistic regression models. These predictors were then included in a searching algorithm with indicators of Wells score, where a series of points were assigned to each predictor. Optimal D-Dimer cutoff values were investigated and incorporated with PECSS to rule out pulmonary embolism. Results In addition to Wells score, PECSS identified seven clinical predictors (anhelation, abnormal blood pressure, in critical condition when admitted, age > 65 years and high levels of pro-BNP, CRP and UA,) strongly associated with pulmonary embolism. Patients can be safely ruled out of pulmonary embolism if PECSS ≤ 4, or if 4

Abstract Food digestion requires the cooperation of different digestive organs. The differentiation of digestive organs is crucial for larvae to start feeding. Therefore, during digestive organogenesis, cell identity and the tissue morphogenesis must be tightly coordinated but how this is accomplished is poorly understood. Here, we demonstrate that WD repeat domain 5 (Wdr5)-mediated H3K4 tri-methylation (H3K4me3) coordinately regulates cell differentiation, proliferation and apoptosis in zebrafish organogenesis of three major digestive organs including intestine, liver, and exocrine pancreas. During zebrafish digestive organogenesis, some of cells in these organ primordia usually undergo differentiation without apoptotic activity and gradually reduce their proliferation capacity. In contrast, cells in the three digestive organs of wdr5 −/− mutant embryos retain progenitor-like status with high proliferation rates, and undergo apoptosis. Wdr5 is a core member of COMPASS complex to implement H3K4me3 and its expression is enriched in digestive organs from 2 days post-fertilization (dpf). Further analysis reveals that lack of differentiation gene expression is due to significant decreases of H3K4me3 around the transcriptional start sites of these genes; this histone modification also reduces the proliferation capacity in differentiated cells by increasing the expression of apc to promote the degradation of β-Catenin; in addition, H3K4me3 promotes the expression of anti-apoptotic genes such as xiap-like, which modulates p53 activity to guarantee differentiated cell survival. Thus, our findings have discovered a common molecular mechanism for cell fate determination in different digestive organs during organogenesis, and also provided insights to understand mechanistic basis of human diseases in these digestive organs.

This study aims to investigate the role of microRNA let-7f in the dysfunction and degeneration of retinal pigment epithelium (RPE) cells through the induction of senescence and oxidative stress. Furthermore, we explore whether let-7f inhibition can protect these cells against sodium iodate (SI)-induced oxidative stress. Oxidative stress and let-7f expression are reciprocally regulated in retinal pigment epithelial cells. Overexpression of let-7f in ARPE-19 cells induced oxidative stress as demonstrated by increased reactive oxygen species (ROS) production as well as senescence. Inhibition of let-7f successfully protected RPE cells from the detrimental effects induced by SI. In addition, let-7f overexpression induced RPE cellular dysfunction by diminishing their migratory capabilities and reducing the phagocytosis of porcine photoreceptor outer segments (POS). Results were further confirmed in vivo by intravitreal injections of SI and let-7f antagomir in C57BL/6 mice. Our results provide strong evidence that let-7f is implicated in the dysfunction of RPE cells through the induction of senescence and oxidative injury. These findings may help to uncover novel and relevant processes in the pathogenesis of dry AMD.

In recent years, cell migration assays (CMAs) have emerged as a tool to study the migration of cells along with their physiological responses under various stimuli, including both mechanical and bio-chemical properties. CMAs are a generic system in that they support various biological applications, such as wound healing assays. In this paper, we review the development of the CMA in the context of its application to wound healing assays. As such, the wound healing assay will be used to derive the requirements on CMAs. This paper will provide a comprehensive and critical review of the development of CMAs along with their application to wound healing assays. One salient feature of our methodology in this paper is the application of the so-called design thinking; namely we define the requirements of CMAs first and then take them as a benchmark for various developments of CMAs in the literature. The state-of-the-art CMAs are compared with this benchmark to derive the knowledge and technological gap with CMAs in the literature. We will also discuss future research directions for the CMA together with its application to wound healing assays.

Background: Hysteroscopic adhesiolysis effectively restores the anatomical integrity of the uterine cavity in cases of intrauterine adhesions (IUA). However, there is ongoing debate regarding the factors influencing the reproductive outcomes of hysteroscopic adhesiolysis in women with IUA. Methods: One-hundred and thirty-seven patients with IUAs who wanted to become pregnant were enrolled. All patients underwent hysteroscopic adhesiolysis performed by a single experienced surgeon at a tertiary University-affiliated hospital between February 2019 and July 2021. Subsequently, these patients attempted to conceive within the following two years. Patients with concurrent intrauterine diseases such as polyps, submucosal myoma, or IUAs attributed to tuberculosis were excluded from the study. General clinical data were collected and analyzed using univariate and multivariable logistic regression analyses. Results: The clinical pregnancy rate for patients with IUA was 60.6% (83/137), and the live birth rate was 51.8% (71/137). The clinical pregnancy and live birth rates were similar between the in vitro fertilization (IVF) group and the spontaneous conception group. Multivariable logistic regression analysis revealed that patients aged 37 years or older (Odds ratio (OR) 3.928, 95% confidence interval (CI) 1.214–12.710, p = 0.022) or with severe IUA (OR 4.579, 95% CI 1.811–11.578, p = 0.002) were significantly more likely to have a lower clinical pregnancy rate. Similarly, patients aged 37 years or older (OR 3.919, 95% CI 1.147–13.388, p = 0.029) or with severe IUA (OR 5.8, 95% CI 2.129–15.806, p = 0.001) were more likely to have a lower birth rate. Conclusions: Patients’ age and severity of IUA can potentially predict the reproductive outcomes of IUA treatment.