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Abstract Background Our previous study demonstrated that long intergenic noncoding RNA 02454 (LINC02454) may act as an oncogene to promote the proliferation and inhibit the apoptosis of papillary thyroid cancer (PTC) cells. This study was designed to investigate the mechanisms whereby LINC02454 is related to PTC tumorigenesis. Methods Thyroid cancer RNA sequence data were obtained from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules closely associated with PTC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the key pathways, and the maximal clique centrality (MCC) topological method was used to identify the hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to compare expression levels of key genes between PTC samples and normal samples and explore the prognostic value of key genes. The key genes were further validated with GEO dataset. Results The top 5000 variable genes were investigated, followed by an analysis of 8 modules, and the turquoise module was the most positively correlated with the clinical stage of PTC. KEGG pathway analysis found the top two pathways of the ECM − receptor interaction and MAPK signaling pathway. In addition, five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified through the MCC algorithm and KEGG analysis. The expression levels of the five key genes were significantly upregulated in thyroid cancer in both TCGA and GEO datasets, and of these five genes, FN1 and ITGA3 were associated with poor disease-free prognosis. Conclusions Our study identified five key genes and two key pathways associated with LINC02454, which might shed light on the underlying mechanism of LINC02454 action in PTC.

Abstract Epigenetic modifications are crucial for plant development. EFD ( E xine F ormation D efect) encodes a SAM-dependent methyltransferase that is essential for the pollen wall pattern formation and male fertility in Arabidopsis. In this study, we find that the expression of DRM2, a de novo DNA methyltransferase in plants, complements for the defects in efd, suggesting its potential de novo DNA methyltransferase activity. Genetic analysis indicates that EFD functions through HB21, as the knockout of HB21 fully restores fertility in efd mutants. DNA methylation and histone modification analyses reveal that EFD represses the transcription of HB21 through epigenetic mechanisms. Additionally, we demonstrate that HB21 directly represses the expression of genes crucial for pollen formation and anther dehiscence, including CalS5, RPG1/SWEET8, CYP703A2 and NST2. Collectively, our findings unveil a double negative regulatory cascade mediated by epigenetic modifications that coordinates anther development, offering insights into the epigenetic regulation of this process.

Abstract Background Posterior spinal fusion (PSF) for the correction of idiopathic scoliosis is associated with severe postoperative pain. Erector spinae plane block (ESPB) has been proposed to provide analgesia and reduce opioid consumption. We aimed to investigate the effect of bilateral ultrasound-guided single-shot ESPB on postoperative analgesia in pediatric patients undergoing PSF. Methods This double-blinded, randomized controlled trial will enroll 74 AIS patients undergoing elective PSF. Participants will be assigned to the ESPB group or control group at a 1:1 ratio. Patients in the ESPB group will receive ultrasound-guided bilateral ESPB preoperatively, and patients in the control group received sham ESPB using normal saline. The primary joint endpoints are the area under the curve (AUC) of numerical rating scale (NRS) score and opioid consumption in postoperative 24 h. The secondary endpoints are numerical rating scale (NRS) score and opioid consumption at postoperative 0.5, 3, 6, 9, 12, 24, 36, and 48 h, rescue analgesia, recovery outcomes, and adverse events. Discussion At present, studies investigating the effect of ESPB on pediatric patients are still needed. This study focuses on the effect of ESPB on pediatric patients undergoing PSF on postoperative pain control and intends to provide a new strategy of multimodal analgesia management for major spine surgery. Trial registration Chinese Clinical Trial Registry ChiCTR2300074505. Registered on August 8, 2023.

Abstract Background Seed amplification assays (SAA) enable the amplification of pathological misfolded proteins, including α-synuclein (αSyn), in both tissue homogenates and body fluids of Parkinson’s disease (PD) patients. SAA involves repeated cycles of shaking or sonication coupled with incubation periods. However, this amplification scheme has limitations in tracking protein propagation due to repeated fragmentation. Methods We introduced a modified form of SAA, known as Quiescent SAA (QSAA), and evaluated biopsy and autopsy samples from individuals clinically diagnosed with PD and those without synucleinopathies (control group). Brain biopsy samples were obtained from 14 PD patients and 6 controls without synucleinopathies. Additionally, skin samples were collected from 214 PD patients and 208 control subjects. Data were analyzed from April 2019 to May 2023. Results QSAA successfully amplified αSyn aggregates in brain tissue sections from mice inoculated with pre-formed fibrils. In the skin samples from 214 PD cases and 208 non-PD cases, QSAA demonstrated high sensitivity (90.2%) and specificity (91.4%) in differentiating between PD and non-PD cases. Notably, more αSyn aggregates were detected by QSAA compared to immunofluorescence with the pS129-αSyn antibody in consecutive slices of both brain and skin samples. Conclusion We introduced the new QSAA method tailored for in situ amplification of αSyn aggregates in brain and skin samples while maintaining tissue integrity, providing a streamlined approach to diagnosing PD with individual variability. The integration of seeding activities with the location of deposition of αSyn seeds advances our understanding of the mechanism underlying αSyn misfolding in PD.

Abstract Background Moral distress seriously affects professional nurses, and a number of instruments have been developed to measure the level of moral distress. The moral distress thermometer (MDT) is one of the commonly used instruments that can rapidly measure real-time moral distress; however, it remains unclear whether it is still useful in the Chinese cultural context. Aim This study aimed to adapt and validate the MDT among Chinese registered nurses. Research design An online, cross-sectional, survey study of adapting and validating Chinese version of MDT. Participants and research context A total of 182 registered nurses effectively finished this survey. The correlation between MDT score and the score of the moral distress scale-revised version (MDS-R) was used for evaluating convergent validity, and MDT scores of registered nurses who working in different departments and who made different actions to the final question of the MDS-R were compared by using one-way ANOVA to evaluate construct validity. Ethical considerations The Ethics Committee of Chongqing Traditional Chinese Medicine Hospital approved this study. Results The Chinese version of MDT was described as relevant to measure moral distress, with a reported item-level content validity index (I-CVI) and scale-level CVI (S-CVI) of 1. The mean MDT score and mean MDS-R score were 2.54 and 38.66, respectively, and the correlation between these two scores was significantly moderate (r = 0.41). Nurses working different departments reported different levels of moral distress, and those working in intensive care unit reported the highest level of moral distress than those working in other departments (p = 0.04). The MDT scores between nurses who presented different actions to their position were also significantly different, and those who had ever left and those who had considered leaving but did not leave reported significantly higher moral distress. Conclusion The MDT is a reliable, valid, and easy-to-use instrument to rapidly measure the real-time moral distress of registered nurses in China.

Abstract The generation of radiological results from image data represents a pivotal aspect of medical image analysis. The latest iteration of ChatGPT-4, a large multimodal model that integrates both text and image inputs, including dermatoscopy images, histology images, and X-ray images, has attracted considerable attention in the field of radiology. To further investigate the performance of ChatGPT-4 in medical image recognition, we examined the ability of ChatGPT-4 to recognize credible osteosarcoma X-ray images. The results demonstrated that ChatGPT-4 can more accurately diagnose bone with or without significant space-occupying lesions but has a limited ability to differentiate between malignant lesions in bone compared to adjacent normal tissue. Thus far, the current capabilities of ChatGPT-4 are insufficient to make a reliable imaging diagnosis of osteosarcoma. Therefore, users should be aware of the limitations of this technology.

Abstract Previous studies have reported associations between newly diagnosed diabetes and poor outcomes after percutaneous coronary intervention (PCI), but there is limited data focusing on elderly patients (age ≥ 65). This study aimed to analyze the prevalence and clinical implications of newly diagnosed diabetes in elderly patients who underwent PCI. From 2004 to 2021, a total of 2456 elderly patients who underwent invasive PCI at Korea University Guro Hospital were prospectively enrolled and followed up for a median of five years. The primary endpoint was five-year major adverse cardiovascular events (MACE). Cox regression was used to evaluate whether newly diagnosed diabetes impacted on long-term clinical outcomes. Newly diagnosed diabetes was presented in approximately 8.1% to 10.9% of elderly patients who underwent PCI. Those who had a new diagnosis of diabetes had a higher risk of MACE than previously known diabetes (25.28% vs. 19.15%, p = 0.039). After adjusting for significant factors, newly diagnosed diabetes remained an independent predictor of MACE (HR [hazard ratio] 1.64, 95% confidence interval [CI] 1.24–2.17, p

Abstract Background Cancer is characterized by dysregulated cellular metabolism. Thus, understanding the mechanisms underlying these metabolic alterations is important for developing targeted therapies. In this study, we investigated the pro-tumoral effect of PDZ and LIM domain 2 (PDLIM2) downregulation in lung cancer growth and its association with the accumulation of mitochondrial ROS, oncometabolites and the activation of hypoxia-inducible factor-1 (HIF-1) α in the process. Methods Databases and human cancer tissue samples were analyzed to investigate the roles of PDLIM2 and HIF-1α in cancer growth. DNA microarray and gene ontology enrichment analyses were performed to determine the cellular functions of PDLIM2. Seahorse assay, flow cytometric analysis, and confocal microscopic analysis were employed to study mitochondrial functions. Oncometabolites were analyzed using liquid chromatography–mass spectrometry (LC–MS). A Lewis lung carcinoma (LLC) mouse model was established to assess the in vivo function of PDLIM2 and HIF-1α. Results The expression of PDLIM2 was downregulated in lung cancer, and this downregulation correlated with poor prognosis in patients. PDLIM2 highly regulated genes associated with mitochondrial functions. Mechanistically, PDLIM2 downregulation resulted in NF-κB activation, impaired expression of tricarboxylic acid (TCA) cycle genes particularly the succinate dehydrogenase (SDH) genes, and mitochondrial dysfunction. This disturbance contributed to the accumulation of succinate and other oncometabolites, as well as the buildup of mitochondrial reactive oxygen species (mtROS), leading to the activation of hypoxia-inducible factor 1α (HIF-1α). Furthermore, the expression of HIF-1α was increased in all stages of lung cancer. The expression of PDLIM2 and HIF-1α was reversely correlated in lung cancer patients. In the animal study, the orally administered HIF-1α inhibitor, PX-478, significantly reduces PDLIM2 knockdown-promoted tumor growth. Conclusion These findings shed light on the complex action of PDLIM2 on mitochondria and HIF-1α activities in lung cancer, emphasizing the role of HIF-1α in the tumor-promoting effect of PDLIM2 downregulation. Additionally, they provide new insights into a strategy for precise targeted treatment by suggesting that HIF-1α inhibitors may serve as therapy for lung cancer patients with PDLIM2 downregulation.

Abstract Diarrhea and constipation are common health concerns in children. Numerous studies have identified strong association between gut microbiota and digestive-related diseases. But little is known about the gut microbiota that simultaneously affects both diarrhea and constipation or their potential regulatory mechanisms. Stool samples from 618 children (66 diarrhea, 138 constipation, 414 healthy controls) aged 0–3 years were collected to investigate gut microbiota changes using 16S rRNA sequencing. Compared with healthy, children with diarrhea exhibited a significant decrease in microbial diversity, while those with constipation showed a marked increase (p

Abstract Depression is a prevalent mental disorder with a complex biological mechanism. Following the rapid development of systems biology technology, a growing number of studies have applied proteomics and metabolomics to explore the molecular profiles of depression. However, a standardized resource facilitating the identification and annotation of the available knowledge from these scattered studies associated with depression is currently lacking. This study presents ProMENDA, an upgraded resource that provides a platform for manual annotation of candidate proteins and metabolites linked to depression. Following the establishment of the protein dataset and the update of the metabolite dataset, the ProMENDA database was developed as a major extension of its initial release. A multi-faceted annotation scheme was employed to provide comprehensive knowledge of the molecules and studies. A new web interface was also developed to improve the user experience. The ProMENDA database now contains 43,366 molecular entries, comprising 20,847 protein entries and 22,519 metabolite entries, which were manually curated from 1370 human, rat, mouse, and non-human primate studies. This represents a significant increase (more than 7-fold) in molecular entries compared to the initial release. To demonstrate the usage of ProMENDA, a case study identifying consistently reported proteins and metabolites in the brains of animal models of depression was presented. Overall, ProMENDA is a comprehensive resource that offers a panoramic view of proteomic and metabolomic knowledge in depression. ProMENDA is freely available at https://menda.cqmu.edu.cn .

Abstract The Hendra and Nipah viruses (HNVs) are highly pathogenic pathogens without approved interventions for human use. In addition, the interaction pattern between the attachment (G) and fusion (F) glycoproteins required for virus entry remains unclear. Here, we isolate a panel of Macaca-derived G-specific antibodies that cross-neutralize HNVs via multiple mechanisms. The most potent antibody, 1E5, confers adequate protection against the Nipah virus challenge in female hamsters. Crystallography demonstrates that 1E5 has a highly similar binding pattern to the receptor. In cryo-electron microscopy studies, the tendency of 1E5 to bind to the upper or lower heads results in two distinct quaternary structures of G. Furthermore, we identify the extended outer loop β1S2-β1S3 of G and two pockets on the apical region of fusion (F) glycoprotein as the essential sites for G-F interactions. This work highlights promising drug candidates against HNVs and contributes deeper insights into the viruses.

Abstract The pathogenesis of major depressive disorder (MDD) involves lipid metabolism. Our earlier research also revealed that MDD patients had much lower total cholesterol (TC) concentrations than healthy controls (HCs). However, it is still unclear why TC decreased in MDD. Here, based on the Ingenuity Knowledge Base’s ingenuity pathway analysis, we found that sodium voltage-gated channel alpha subunit 11A (SCN11A) might serve as a link between low lipid levels and MDD. We analyzed the TC levels and used ELISA kits to measure the levels of SCN11A in the serum from 139 MDD patients, and 65 HCs to confirm this theory and explore the potential involvement of SCN11A in MDD. The findings revealed that TC levels were considerably lower and SCN11A levels were remarkably increased in MDD patients than those in HCs, while they were significantly reversed in drug-treatment MDD patients than in drug-naïve MDD patients. There was no significant difference in SCN11A levels among MDD patients who used single or multiple antidepressants, and selective serotonin reuptake inhibitors or other antidepressants. Pearson correlation analysis showed that the levels of TC and SCN11A were linked with the Hamilton Depression Rating Scales score. A substantial association was also found between TC and SCN11A. Moreover, a discriminative model made up of SCN11A was discovered, which produced an area under a curve of 0.9571 in the training set and 0.9357 in the testing set. Taken together, our findings indicated that SCN11A may serve as a link between low lipid levels and MDD, and showed promise as a candidate biomarker for MDD.

Wireless Sensor Network (WSN) is a distributed sensor network composed a large number of nodes with low cost, low performance and self-management. The special structure of WSN brings both convenience and vulnerability. For example, a malicious participant can launch attacks by capturing a physical device. Therefore, node authentication that can resist malicious attacks is very important to network security. Recently, blockchain technology has shown the potential to enhance the security of the Internet of Things (IoT). In this paper, we propose a Blockchain-empowered Authentication Scheme (BAS) for WSN. In our scheme, all nodes are managed by utilizing the identity information stored on the blockchain. Besides, the simulation experiment about worm detection is executed on BAS, and the security is evaluated from detection and infection rate. The experiment results indicate that the proposed scheme can effectively inhibit the spread and infection of worms in the network.

Abstract Essential amino acids (EAA) and microRNAs (miRs) control biological activity of a cell. Whether EAA regulates the activity of miR has never been demonstrated. Here, as proof‐of‐concept, a tryptophan (Trp, an EAA) complex containing Argonaute 2 (Ago2) and miRs including miR‐193a (Trp/Ago2/miR‐193a) is identified. Trp binds miR‐193a‐3p and interacts with Ago2. Trp/Ago2/miR‐193a increases miR‐193a‐3p activity via enhancing Argonaute 2 (Ago2) RNase activity. Other miRs including miR‐103 and miR‐107 in the Trp complex enhance miR‐193a activity by targeting the same genes. Mechanistically, the Trp/Ago2/miR‐193a complex interacts with Trp‐binding pockets of the PIWI domain of Ago2 to enhance Ago2 mediated miR activity. This newly formed Ago2/Trp/miR‐193a‐3p complex is more efficient than miR‐193a‐3p alone in inhibiting the expression of targeted genes and inhibiting colon cancer liver metastasis. The findings show that Trp regulates miR activity through communication with the RNA‐induced silencing complexes (RISC), which provides the basis for tryptophan based miR therapy.

BackgroundLung cancer associated with cystic airspaces is a rare disease, and a rare imaging performance of non-small cell lung cancer. Due to the lack of conventional diagnosis methods, it is difficult to rely on imaging diagnosis. Therefore, the definitive diagnosis of these neoplastic lesions remains challenging.Case presentationWe summarize the follow-up and diagnosis of a rare cystic airspaces lung metastatic carcinoma in an elderly man with annular density shadow in the right inferior lobe 2 years after surgery for squamous cell carcinoma in the left inferior lobe.ResultsDuring the follow-up of the patient, after the lesion of the lower lobe of the right lung was enlarged, the structural and imaging characteristics were identified, and a special method was selected, namely biopsy of the lesion under the electromagnetic navigation bronchoscope, for clear diagnosis and subsequent treatment.ConclusionFor pulmonary cystic airspaces, it is important to correctly identify their imaging features. Because of the possibility of malignancy, it is essential to stop the radiological study in time and to acquire the pathological diagnosis by an appropriate method.

Acute intermittent porphyria (AIP) is caused by mutations in the gene encoding hydroxymethylbilane synthase (HMBS), a key enzyme in the heme biosynthesis pathway. AIP is an autosomal dominant disorder characterized by low penetrance and a highly heterogenous clinical presentation. The estimated prevalence of AIP is 5–10 cases per 100,000 persons, with acute attacks manifesting in less than 1% of the at-risk population. This low frequency of attacks suggests significant roles for oligogenic inheritance and environmental factors in the pathogenesis of the disease. In recent years, identification of several modifier genes has advanced our understanding of the factors influencing AIP penetrance and disease severity. This review summarizes these factors including the impact of specific HMBS mutations, oligogenic inheritance, mitochondrial DNA copy number, age, sex, the influence of sex hormones, and the role of environmental factors. Further studies into the etiology of AIP disease penetrance should inform pathogenesis, potentially allowing for the development of more precise diagnostic and therapeutic approaches.

BackgroundThe ongoing global health crisis of COVID-19, and particularly the challenges posed by recurrent infections of the Omicron variant, have significantly strained healthcare systems worldwide. There is a growing body of evidence indicating an increased susceptibility to Omicron infection in patients suffering from Acute Kidney Injury (AKI). However, the intricate molecular interplay between AKI and Omicron variant of COVID-19 remains largely enigmatic.MethodsThis study employed a comprehensive analysis of human RNA sequencing (RNA-seq) and microarray datasets to identify differentially expressed genes (DEGs) associated with Omicron infection in the context of AKI. We engaged in functional enrichment assessments, an examination of Protein-Protein Interaction (PPI) networks, and advanced network analysis to elucidate the cellular signaling pathways involved, identify critical hub genes, and determine the relevant controlling transcription factors and microRNAs. Additionally, we explored protein-drug interactions to highlight potential pharmacological interventions.ResultsOur investigation revealed significant DEGs and cellular signaling pathways implicated in both Omicron infection and AKI. We identified pivotal hub genes, including EIF2AK2, PLSCR1, GBP1, TNFSF10, C1QB, and BST2, and their associated regulatory transcription factors and microRNAs. Notably, in the murine AKI model, there was a marked reduction in EIF2AK2 expression, in contrast to significant elevations in PLSCR1, C1QB, and BST2. EIF2AK2 exhibited an inverse relationship with the primary AKI mediator, Kim-1, whereas PLSCR1 and C1QB demonstrated strong positive correlations with it. Moreover, we identified potential therapeutic agents such as Suloctidil, Apocarotenal, 3′-Azido-3′-deoxythymidine, among others. Our findings also highlighted a correlation between the identified hub genes and diseases like myocardial ischemia, schizophrenia, and liver cirrhosis. To further validate the credibility of our data, we employed an independent validation dataset to verify the hub genes. Notably, the expression patterns of PLSCR1, GBP1, BST2, and C1QB were consistent with our research findings, reaffirming the reliability of our results.ConclusionOur bioinformatics analysis has provided initial insights into the shared genetic landscape between Omicron COVID-19 infections and AKI, identifying potential therapeutic targets and drugs. This preliminary investigation lays the foundation for further research, with the hope of contributing to the development of innovative treatment strategies for these complex medical conditions.

Leakage failure occurred in the reheater pipe of a subcritical unit after 9 years operation, but didn't reach the design lifespan. Multi test and analysis methods were applied to find the failure reason and mechanism. The results show that the main failure mode is the thinning of the pipe wall caused by high temperature corrosion, the metal loss of the pipe wall is more than 25 %. Through the analysis of the structure and composition of the corrosion products, it is found that the corrosion products of the pipe wall are divided into three layers, while a large number of pores exist between the corrosion products and base material, hereby, the corrosive substances can continuously reach the surface of the base material. The content of sulfur and oxygen in the corrosion layer on the side of pipe wall is high, and the percentage reaches 20.95 % and 49.17 % respectively. It is proved that sulfur is the main factor affecting the high temperature corrosion of reheater pipes, and sulfate is produced by the combined action of sulfur and oxygen. Under the continuous action of high temperature sulfur corrosion, the local pipe wall of the pipeline is thinned and eventually leaks.

Abstract Background The relationship between the gut mycobiome and end-stage renal disease (ESRD) remains largely unexplored. Methods In this study, we compared the gut fungal populations of 223 ESRD patients and 69 healthy controls (HCs) based on shotgun metagenomic sequencing data, and analyzed their associations with host serum and fecal metabolites. Results Our findings revealed that ESRD patients had a higher diversity in the gut mycobiome compared to HCs. Dysbiosis of the gut mycobiome in ESRD patients was characterized by a decrease of Saccharomyces cerevisiae and an increase in various opportunistic pathogens, such as Aspergillus fumigatus, Cladophialophora immunda, Exophiala spinifera, Hortaea werneckii, Trichophyton rubrum, and others. Through multi-omics analysis, we observed a substantial contribution of the gut mycobiome to host serum and fecal metabolomes. The opportunistic pathogens enriched in ESRD patients were frequently and positively correlated with the levels of creatinine, homocysteine, and phenylacetylglycine in the serum. The populations of Saccharomyces, including the HC-enriched Saccharomyces cerevisiae, were frequently and negatively correlated with the levels of various toxic metabolites in the feces. Conclusions Our results provided a comprehensive understanding of the associations between the gut mycobiome and the development of ESRD, which had important implications for guiding future therapeutic studies in this field.

As an important supplement to traditional airborne synthetic aperture radar (SAR), multirotor unmanned aerial vehicle (UAV) SAR has the advantages of low cost, high flexibility, and strong survival ability. However, due to the complex motion and flight characteristics of the multirotor UAV platform, multirotor UAV SAR faces challenges, including spatially variant low-frequency (LF) errors and severe high-frequency (HF) errors. To deal with these problems, an improved motion compensation approach is proposed for multirotor UAV SAR imaging, which is implemented through two processing steps. 1) The LF errors are eliminated by an improved two-step MoCo approach, which takes into account the spatial variations of both envelope and phase. 2) The HF errors are estimated and corrected by an extended phase gradient autofocus scheme. Different from conventional solutions, our approach can effectively remove the complex motion errors of multirotor UAV SAR step-by-step with high robustness even in high-resolution scenarios. Computer simulation and experimental results verify the effectiveness of our approach.

Abstract The electrochemical conversion of nitrate to ammonia is a way to eliminate nitrate pollutant in water. Cu-Co synergistic effect was found to produce excellent performance in ammonia generation. However, few studies have focused on this effect in high-entropy oxides. Here, we report the spin-related Cu-Co synergistic effect on electrochemical nitrate-to-ammonia conversion using high-entropy oxide Mg0.2Co0.2Ni0.2Cu0.2Zn0.2O. In contrast, the Li-incorporated MgCoNiCuZnO exhibits inferior performance. By correlating the electronic structure, we found that the Co spin states are crucial for the Cu-Co synergistic effect for ammonia generation. The Cu-Co pair with a high spin Co in Mg0.2Co0.2Ni0.2Cu0.2Zn0.2O can facilitate ammonia generation, while a low spin Co in Li-incorporated MgCoNiCuZnO decreases the Cu-Co synergistic effect on ammonia generation. These findings offer important insights in employing the synergistic effect and spin states inside for selective catalysis. It also indicates the generality of the magnetic effect in ammonia synthesis between electrocatalysis and thermal catalysis.

Abstract Retinoblastoma (RB) is the most prevalent ocular tumor of childhood, and its extraocular invasion significantly increases the risk of metastasis. Nevertheless, a single-cell characterization of RB local extension has been lacking. Here, we perform single-cell RNA sequencing on four RB samples (two from intraocular and two from extraocular RB patients), and integrate public datasets of five normal retina samples, four intraocular samples, and three extraocular RB samples to characterize RB local extension at the single-cell level. A total of 128,454 qualified cells are obtained in nine major cell types. Copy number variation inference reveals chromosome 6p amplification in cells derived from extraocular RB samples. In cellular heterogeneity analysis, we identified 10, 8, and 7 cell subpopulations in cone precursor like cells, retinoma like cells, and MKI67+ photoreceptorness decreased (MKI67+ PhrD) cells, respectively. A high expression level of SOX4 was detected in cells from extraocular samples, especially in MKI67+ PhrD cells, which was verified in additional clinical RB samples. These results suggest that SOX4 might drive RB local extension. Our study presents a single-cell transcriptomic landscape of intraocular and extraocular RB samples, improving our understanding of RB local extension at the single-cell resolution and providing potential therapeutic targets for RB patients.

Abstract Background & aims The present study utilized extracted computed tomography radiomics features to classify the gross tumor volume and normal liver tissue in hepatocellular carcinoma by mainstream machine learning methods, aiming to establish an automatic classification model. Methods We recruited 104 pathologically confirmed hepatocellular carcinoma patients for this study. GTV and normal liver tissue samples were manually segmented into regions of interest and randomly divided into five-fold cross-validation groups. Dimensionality reduction using LASSO regression. Radiomics models were constructed via logistic regression, support vector machine (SVM), random forest, Xgboost, and Adaboost algorithms. The diagnostic efficacy, discrimination, and calibration of algorithms were verified using area under the receiver operating characteristic curve (AUC) analyses and calibration plot comparison. Results Seven screened radiomics features excelled at distinguishing the gross tumor area. The Xgboost machine learning algorithm had the best discrimination and comprehensive diagnostic performance with an AUC of 0.9975 [95% confidence interval (CI): 0.9973–0.9978] and mean MCC of 0.9369. SVM had the second best discrimination and diagnostic performance with an AUC of 0.9846 (95% CI: 0.9835– 0.9857), mean Matthews correlation coefficient (MCC)of 0.9105, and a better calibration. All other algorithms showed an excellent ability to distinguish between gross tumor area and normal liver tissue (mean AUC 0.9825, 0.9861,0.9727,0.9644 for Adaboost, random forest, logistic regression, naivem Bayes algorithm respectively). Conclusion CT radiomics based on machine learning algorithms can accurately classify GTV and normal liver tissue, while the Xgboost and SVM algorithms served as the best complementary algorithms.

Abstract Our previous work has shown that d-ribose (RIB)-induced depressive-like behaviors in mice. However, the relationship between variations in RIB levels and depression as well as potential RIB participation in depressive disorder is yet unknown. Here, a reanalysis of metabonomics data from depressed patients and depression model rats is performed to clarify whether the increased RIB level is positively correlated with the severity of depression. Moreover, we characterize intestinal epithelial barrier damage, gut microbial composition and function, and microbiota-gut-brain metabolic signatures in RIB-fed mice using colonic histomorphology, 16 S rRNA gene sequencing, and untargeted metabolomics analysis. The results show that RIB caused intestinal epithelial barrier impairment and microbiota-gut-brain axis dysbiosis. These microbial and metabolic modules are consistently enriched in peripheral (fecal, colon wall, and serum) and central (hippocampus) glycerophospholipid metabolism. In addition, three differential genera (Lachnospiraceae_UCG-006, Turicibacter, and Akkermansia) and two types of glycerophospholipids (phosphatidylcholine and phosphatidylethanolamine) have greater contributions to the overall correlations between differential genera and glycerophospholipids. These findings suggest that the disturbances of gut microbiota by RIB may contribute to the onset of depressive-like behaviors via regulating glycerophospholipid metabolism, and providing new insight for understanding the function of microbiota-gut-brain axis in depression.

Currently, the standard treatment for patients who have undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (MI) involves dual antiplatelet therapy (DAPT) with a combination of aspirin and a potent P2Y12 receptor inhibitor. However, the potential benefits of aspirin were partially constrained by the intolerance of some patients. The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.This retrospective study was conducted at a single center and utilized propensity score matching. The enrollment spanned from January 2019 to June 2022, incorporating patients with AMI after PCI. The participants were categorized into two groups based on discharged prescriptions: the aspirin DAPT group and the indobufen DAPT group. The primary endpoint focused on net adverse clinical event (NACE), defined as a composite outcome, including cardiac death, recurrence of MI, definite or probable stent thrombosis (ST), target lesion revascularization (TLR), ischemic stroke and Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5. All the patients underwent a one-year follow-up period.A total of 1451 patients were enrolled in this study, with 258 assigned to the indobufen DAPT group and 1193 to the aspirin DAPT group. Following 1:1 propensity score matching, 224 patients were retained in each group. In the indobufen DAPT group, 58 individuals (25.9%) experienced the primary endpoint within one year, compared to 52 individuals (23.2%) in the aspirin DAPT group (HR 1.128, 95% CI 0.776–1.639, p = .527). Specifically, no significant differences were observed in either the efficacy endpoint (MACCE, 20.1% vs. 14.7%, HR 1.392, 95% CI 0.893–2.170, p = .146) or the safety endpoint (BARC 2,3 or 5, 8.04% vs. 10.30%, HR 0.779, p = .427). These findings remained consistent at 1, 3, or 6 months. Additionally, the incidence of gastrointestinal symptoms were significantly lower in indobufen DAPT group compared to the aspirin DAPT group (7.1% vs. 14.3%, p = .022).Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.

BackgroundLarge Hemispheric Infarction (LHI) poses significant mortality and morbidity risks, necessitating predictive models for in-hospital mortality. Previous studies have explored LHI progression to malignant cerebral edema (MCE) but have not comprehensively addressed in-hospital mortality risk, especially in non-decompressive hemicraniectomy (DHC) patients.MethodsDemographic, clinical, risk factor, and laboratory data were gathered. The population was randomly divided into Development and Validation Groups at a 3:1 ratio, with no statistically significant differences observed. Variable selection utilized the Bonferroni-corrected Boruta technique (p

Amino acid-derived quaternary ammonium salts were successfully applied in the asymmetric aza-Henry reaction of nitromethane to N-Boc trifluoromethyl ketimines. α-Trifluoromethyl β-nitroamines were synthesized in good to excellent yields with moderate to good enantioselectivities. This reaction is distinguished by its mild conditions, low catalyst loading (1 mol%), and catalytic base. It also proceeded on a gram scale without loss of enantioselectivity. The products were transformed to a series of adamantane-type compounds containing chiral trifluoromethylamine fragments. The potent anticancer activities of these compounds against liver cancer HepG2 and melanoma B16F10 were evaluated. Six promising compounds with notable efficacy have potential for further development.

Uniportal video-assisted thoracoscopic surgery (UVATS) segmentectomy has emerged as an effective approach for managing early-stage non-small-cell lung cancer (NSCLC). Compared to conventional open and thoracoscopic surgeries, this minimally invasive surgical technique offers multiple benefits, including reduced postoperative discomfort, shorter hospital stays, expedited recovery, fewer complications, and superior cosmetic outcomes. Particularly advantageous in preserving lung function, UVATS segmentectomy is a compelling option for patients with compromised lung capabilities or limited pulmonary reserve. Notably, it demonstrates promising oncological results in early-stage NSCLC, with long-term survival rates comparable to those of lobectomies. Skilled thoracic surgeons can ensure a safe and effective execution of UVATS despite the potential technical challenges posed by complex tumor locations that may hinder visibility and maneuverability within the thoracic cavity. This study provided a comprehensive review of the literature and existing studies on UVATS segmentectomies. It delves into the evolution of the technique, its current applications, and the balance between its benefits and limitations. This discussion extends the technical considerations, challenges, and prospects of UVATS segmentectomy. Furthermore, it aimed to update advancements in segmentectomy for treating early-stage NSCLC, offering in-depth insights to thoracic surgeons to inform more scientifically grounded and patient-specific surgical decisions.

BackgroundThe tertiary lymphatic structure (TLS) is an important component of the tumor immune microenvironment and has important significance in patient prognosis and response to immune therapy. However, the underlying mechanism of TLS in soft tissue sarcoma remains unclear.MethodsA total of 256 RNAseq and 7 single-cell sequencing samples were collected from TCGA-SARC and GSE212527 cohorts. Based on published TLS-related gene sets, four TLS scores were established by GSVA algorithm. The immune cell infiltration was calculated via TIMER2.0 and “MCPcounter” algorithms. In addition, the univariate, LASSO, and multivariate-Cox analyses were used to select TLS-related and prognosis-significant hub genes. Single-cell sequencing dataset, clinical immunohistochemical, and cell experiments were utilized to validate the hub genes.ResultsIn this study, four TLS-related scores were identified, and the total-gene TLS score more accurately reflected the infiltration level of TLS in STS. We further established two hub genes (DUSP9 and TNFSF14) prognosis markers and risk scores associated with soft tissue sarcoma prognosis and immune therapy response. Flow cytometry analysis showed that the amount of CD3, CD8, CD19, and CD11c positive immune cell infiltration in the tumor tissue dedifferentiated liposarcoma patients was significantly higher than that of liposarcoma patients. Cytological experiments showed that soft tissue sarcoma cell lines overexpressing TNFSF14 could inhibit the proliferation and migration of sarcoma cells.ConclusionThis study systematically explored the TLS and related genes from the perspectives of bioinformatics, clinical features and cytology experiments. The total-gene TLS score, risk score and TNFSF14 hub gene may be useful biomarkers for predicting the prognosis and immunotherapy efficacy of soft tissue sarcoma.

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.

Abstract Amorphous porous organic polymers (aPOPs) are a type of highly crosslinked polymers. These polymers are generally constructed from rigid organic building blocks, which have become an important subclass of POPs with diverse applications. In the early stage of development, a wide range of carbon-based building blocks and network forming chemistry afforded a large library of aPOPs with rich structures and properties. Recently, implanting main group elements with diverse geometric structures and electronic configurations into aPOPs has proven to be a useful tool to fine-tune the structures and properties of these polymers. Herein, we outline the recent advances in the field of main group (MG)-aPOPs where main-group elements either played unique roles in tuning the structures and properties of MG-aPOPs, or offered new strategies in the synthesis of MG-aPOPs. Furthermore, this Review discusses various challenges remaining in the field from the perspectives of synthetic strategies and characterization techniques, and presents some specific studies that may potentially address the challenges.

Abstract Core genome multilocus sequence typing (cgMLST) is commonly used to classify bacterial strains into different types, for taxonomical and epidemiological applications. However, cgMLST schemes require central databases for the nomenclature of new alleles and sequence types, which must be synchronized worldwide and involve increasingly intensive calculation and storage demands. Here, we describe a distributed cgMLST (dcgMLST) scheme that does not require a central database of allelic sequences and apply it to study evolutionary patterns of epidemic and endemic strains of the genus Neisseria. We classify 69,994 worldwide Neisseria strains into multi-level clusters that assign species, lineages, and local disease outbreaks. We divide Neisseria meningitidis into 168 endemic lineages and three epidemic lineages responsible for at least 9 epidemics in the past century. According to our analyses, the epidemic and endemic lineages experienced very different population dynamics in the past 100 years. Epidemic lineages repetitively emerged from endemic lineages, disseminated worldwide, and apparently disappeared rapidly afterward. We propose a stepwise model for the evolutionary trajectory of epidemic lineages in Neisseria, and expect that the development of similar dcgMLST schemes will facilitate epidemiological studies of other bacterial pathogens.

Background: Ginsenoside Rg1 has been studied to improve systemic inflammatory injury induced by sepsis, but its mechanism is not fully understood. The objective of this study was to explore the potential molecular mechanism by which Rg1 ameliorates septic intestinal barrier function impairment. Results: Rg1 administration or miR-30e-5p upregulation alleviated LPS-induced apoptosis of Caco2 cells, decreased LDH and inflammatory cytokines levels, enhanced cell proliferation, promoted tight junction protein expression, and inhibited p65 phosphorylation. These beneficial effects of Rg1 were compensated by miR-30e-5p knockdown or FBXO11 overexpression. Animal studies have also yielded consistent results. Mechanistically, Rg1 performed this role by upregulating miR-30e-5p and inhibiting FBXO11 expression. Conclusions: Rg1 protects intestinal barrier function in sepsis by regulating the miR-30e-5p/FBXO11 axis. These data provide new insights into the development of targeted agents for septic intestinal injury and the understanding of Rg1's therapeutic mechanisms. How to cite:: Zhu W, Fan D, Zhou Z, et al. Ginsenoside protects intestinal barrier function and improves epithelium injury in sepsis by regulating the miR-30e-5p/FBXO11 axis. Electron J Biotechnol 2023;66. https://doi.org/10.1016/j.ejbt.2023.07.001.

This study investigates the application of deep learning models—specifically Deep Neural Networks (DNN), Long Short-Term Memory (LSTM), and Long Short-Term Memory Neural Networks (LSTM-NN)—to predict panel flutter in aerospace structures. The goal is to improve the accuracy and efficiency of predicting aeroelastic behaviors under various flight conditions. Utilizing a supersonic flat plate as the main structure, the research integrates various flight conditions into the aeroelastic equation. The resulting structural vibration data create a large-scale database for training the models. The dataset, divided into training, validation, and test sets, includes input features such as panel aspect ratio, Mach number, air density, and decay rate. The study highlights the importance of selecting appropriate hidden layers, epochs, and neurons to avoid overfitting. While DNN, LSTM, and LSTM-NN all showed improved training with more neurons and layers, excessive numbers beyond a certain point led to diminished accuracy and overfitting. Performance-wise, the LSTM-NN model achieved the highest accuracy in classification tasks, effectively capturing sequential features and enhancing classification precision. Conversely, LSTM excelled in regression tasks, adeptly handling long-term dependencies and complex non-linear relationships, making it ideal for predicting flutter Mach numbers. Despite LSTM’s higher accuracy, it required longer training times due to increased computational complexity, necessitating a balance between accuracy and training duration. The findings demonstrate that deep learning, particularly LSTM-NN, is highly effective in predicting panel flutter, showcasing its potential for broader aerospace engineering applications. By optimizing model architecture and training processes, deep learning models can achieve high accuracy in predicting critical aeroelastic phenomena, contributing to safer and more efficient aerospace designs.

This study introduces an innovative energy harvesting system designed for industrial applications such as fluid pipelines, air conditioning ducts, sewer systems, and subsea oil pipelines. The system integrates magneto-electric flow coupling and utilizes a dynamic vibration absorber (DVA) to mitigate the vibrations induced by fluid flow while simultaneously harvesting energy through magnetic dipole–dipole interactions in a vibration energy harvester (VEH). The theoretical models, based on Hamilton’s Principle and the Biot–Savart Law, were validated through comprehensive experiments. The results indicate the superior performance of the small-magnet system over the large-magnet system in both damping and power generation. The study analyzed the frequency response and energy conversion efficiency across different parameters, including the DVA mass, spring constant, and placement location. The experimental findings demonstrated significant vibration reduction and increased voltage output, validating the theoretical model. This research offers new avenues for energy harvesting systems in pipeline infrastructures, potentially enhancing energy efficiency and structural integrity.

Obesity is a multifactorial chronic inflammatory metabolic disorder, with pathogenesis influenced by genetic and non-genetic factors such as environment and diet. Intestinal microbes and their metabolites play significant roles in the occurrence and development of obesity by regulating energy metabolism, inducing chronic inflammation, and impacting intestinal hormone secretion. Epigenetics, which involves the regulation of host gene expression without changing the nucleotide sequence, provides an exact direction for us to understand how the environment, lifestyle factors, and other risk factors contribute to obesity. DNA methylation, as the most common epigenetic modification, is involved in the pathogenesis of various metabolic diseases. The epigenetic modification of the host is induced or regulated by the intestinal microbiota and their metabolites, linking the dynamic interaction between the microbiota and the host genome. In this review, we examined recent advancements in research, focusing on the involvement of intestinal microbiota and DNA methylation in the etiology and progression of obesity, as well as potential interactions between the two factors, providing novel perspectives and avenues for further elucidating the pathogenesis, prevention, and treatment of obesity.

Household energy consumption plays a critical role in the context of global climate change. Utilizing data from the 2018 China Social Survey (CGSS), this study empirically examined the impact of subjective socioeconomic status (SES) on household green energy consumption behaviors using probit and ordered probit models. The mechanism of influence was further analyzed through the mediated effect approach. The results found include the following: (1) Although the proportion of households participating in green energy policies is similar to those not participating, the proportion of households deeply participating in multiple policies is very low; (2) subjective SES significantly influences both the rate and depth of household participation in green energy policies; (3) internet usage and understanding of green energy policies serve as mediating mechanisms for the promotive effect of subjective SES; and (4) subjective SES showed significant heterogeneity in its effects on different gender and education level groups. These findings contribute to the understanding of the drivers of household green energy use decisions and provide an important reference for governmental policymaking to enhance participation rates and degrees in green energy participation. Implications of these findings highlight the potential for targeted policies that address internet accessibility and educational outreach, which could significantly enhance the effectiveness of green energy initiatives across diverse socioeconomic groups.