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The arrival of the metaverse, as a new generation of information technology, will bring great changes to people's production, life, and learning. The educational metaverse is regarded as a new form of educational development, which will bring a transformative impact on educational teaching activities. In this context, this study has developed a general architecture of educational metaverse system, which includes the physical layer, software layer, data layer, and application layer, based on the technical, theoretical, and architectural support and its digital ecology of educational metaverse system construction. The study has tried to construct a physiology virtual experimental teaching system and taken the rabbit's exercise of respiration regulation experiment as an example to start the research on the educational metaverse in physiology experimental teaching. Participants of the study were 120 students from the 2019 clinical medicine class at School A. By analyzing the learning outcome of students in the virtual experiment course of the educational metaverse, it is concluded that educational metaverse can promote both teaching and learning in the process of experimental teaching; this research has explored the path for the new form of Internet education, which is of great significance for promoting the efficient construction of new education infrastructure and the innovative development of education modernization.

Poplar stands as one of the primary afforestation trees globally. We successfully generated transgenic poplar trees characterized by enhanced biomass under identical nutrient conditions, through the overexpression of the pivotal nitrogen assimilation gene, pxAlaAT3. An environmental risk assessment was conducted for investigate the potential changes in rhizosphere soil associated with these overexpressing lines (OL). The results show that acid phosphatase activity was significantly altered under ammonium in OL compared to the wild-type control (WT), and a similar difference was observed for protease under nitrate. 16SrDNA sequencing indicated no significant divergence in rhizosphere soil microbial community diversity between WT and OL. Metabolomics analysis revealed that the OL caused minimal alterations in the metabolites of the rhizosphere soil, posing no potential harm to the environment. With these findings in mind, we anticipate that overexpressed plants will not adversely impact the surrounding soil environment.

Grape production is an important part of the agricultural economy, which has economic and widespread social benefits. Monitoring and evaluation of grape berries during growth is an important guarantee for the production of high-quality grape berries. Traditional testing techniques are time-consuming, laborious and destructive, while non-destructive testing techniques represented by hyperspectral technology can successfully solve this problem. This paper summarizes recent progress in the application of hyperspectral technology in grape shape measurement, chemical substance detection, ripeness discrimination and defects and damage identification. It also analyzes the advantages and disadvantages of hyperspectral technology in the detection of different quality indexes, and discusses the potential of and prospects for the application of hyperspectral technology in the detection of grape quality, which is aimed at providing a reference to the research and developing non-destructive techniques for the quality detection of grape berry.

Abstract Impending myasthenic crisis (IMC) is an emergent situation requiring aggressive management to prevent patients from developing myasthenic crisis (MC) in patients with myasthenia gravis (MG). Efgartigimod has been proved to be well tolerated and efficacious in MG patients. The present study aimed to compare the efficacy of efgartigimod and intravenous immunoglobulin (IVIg) in rescuing IMC. IMC patients treated with efgartigimod or IVIg were retrospectively enrolled. The primary outcome was determined as the mean change in MG activities of daily living (MG-ADL) score from baseline to week 1 and 4 after treatment, respectively. Safety was assessed based on medical records during the hospitalization to monitor the adverse events. A total of 9 patients treated with efgartigimod and 10 patients treated with IVIg were enrolled. There were no significant differences in the clinical characteristics at baseline between the two groups (P > 0.05). Compared with the IVIg group, the efgartigimod group had a greater reduction in the MG-ADL score at week 1 (P = 0.035) and week 4 (P = 0.005). One patient in the efgartigimod group had an upper respiratory infection. These findings suggest that efgartigimod is a treatment option for IMC in addition to IVIg and plasma exchange.

Abstract Magnetic resonance imaging contrast agents can enhance diagnostic precision but often face limitations such as short imaging windows, low tissue specificity, suboptimal contrast enhancement, or potential toxicity, which affect resolution and long-term monitoring. Here, we present a protein contrast agent based on lanmodulin, engineered with a single-point mutation at position 108 from N to D to yield maximum gadolinium binding sites. After loading with Gd3+ ions, the resulting protein complex, LanND-Gd, exhibits efficient renal clearance, high relaxivity, and prolonged renal retention compared to commercial agents. LanND-Gd enables high-performance visualization of whole-body structures and brain vasculature in male mice at a resolution finer than one hundred micrometers. In male ischemia mouse models, LanND-Gd also improves kidney dysfunction monitoring while minimizing risks of neural toxicity or immunogenic reactions. This protein-based contrast agent offers superior image quality, improved biocompatibility, and extended imaging timeframes, promising significant advancements in magnetic resonance-based diagnostics and patient outcomes.

The deterioration in fruit quality of commercial tomatoes is a major concern of modern tomato breeding. However, the metabolism and genetics of fruit quality are poorly understood. Here, we performed transgenic and molecular biology experiments to reveal that tomato phytoene synthase 1 (SlPSY1) is responsible for the accumulation of an important flavor chemical, 6-methyl-5-hepten-2-one (MHO). To dissect the function of SlPSY1 in regulating fruit quality, we generated and analyzed a dataset encompassing over 2 000 compounds detected by GC–MS and LC-MS/MS along with transcriptomic data. The combined results illustrated that SlPSY1 deficiency imparts novel flavor to yellow tomatoes with 236 volatiles significantly changed and improves fruit firmness, possibly due to accumulation of seven cutins. Further analysis indicated SlPSY1 is essential for carotenoid-derived metabolite biosynthesis by catalyzing prephytoene-PP (PPPP) to 15-cis-phytoene. Notably, we showed that SlPSY1 can influence the metabolic flux between carotenoid and flavonoid pathways, and this metabolic flux was confirmed by silencing SlCHS1. Our study provided insights into the multiple effects of SlPSY1 on tomato fruit metabolome and highlights the potential to produce high-quality fruit by rational design of SlPSY1 expression.

Abstract Objective Ulcerative colitis (UC) and Hashimoto’s thyroiditis frequently cooccur in patients with multiple autoimmune conditions, but the specific association between UC and hypothyroidism is unknown. We used Mendelian randomization (MR) methods to determine the causal relationship between UC and hypothyroidism. Methods We obtained single nucleotide polymorphisms (SNPs) related to ulcerative colitis (UC) and hypothyroidism from genome-wide association studies (GWAS) available in the public database of the Integrated Epidemiology Unit (IEU). To assess the causal relationship between UC and hypothyroidism, we employed MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode methods. Sensitivity analyses were performed using Cochran’s Q test, the horizontal pleiotropy test, and the leave-one-out (LOO) method to assess the reliability of the MR data. The genes corresponding to instrumental variables (IVs) were subjected to Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of the Genome (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis to explore the mechanisms behind the causal relationships at the gene level. Results Forward MR analysis indicated that hypothyroidism was associated with an increased risk of UC (IVW: P = 0.02, OR = 9.71, 95% confidence interval (CI) = 1.36–69.46). In contrast, reverse MR did not demonstrate a causal relationship between UC and hypothyroidism (IVW: P = 0.53). Sensitivity analysis proved the reliability of the results. The PPI network revealed CD247, CD80, and STAT4 as central genes. GO and KEGG analyses revealed significant enrichment of the T cell, gamma interferon (IFN-γ), and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways. Conclusion Hypothyroidism was a risk factor for UC. The balance of T-cell differentiation played an important role in the process of hypothyroidism-induced UC, and IL-21 might be the key to finding a cure. Enrichment of PD-1/PD-L1 might attenuate inflammation by suppressing the immune action of T cells.

Abstract Background Although the etiology of aneurysms remains elusive, recent advances in high-throughput sequencing technology and ongoing human microbiome investigations suggest a potential link between microbiome composition and the onset of various human diseases. Objective This study aimed to utilize high-throughput 16 S rRNA gene sequencing to analyze the oral flora bacterial profiles of individuals, comparing patients with intracranial aneurysms to a healthy control group. Importantly, we sought to identify differences in the oral microbiota and offer novel insights and methods for early diagnosis and identification of intracranial aneurysms. Method Saliva samples were collected from 60 patients with cerebral aneurysms (case group) and 130 healthy individuals (control group). The V3-V4 region of the bacterial 16 S rRNA gene was amplified and sequenced using the HiSeq high-throughput sequencing platform to establish the bacterial profile. Sequencing data were analyzed using QIIME2 and Metastats software to compare composition differences and relative abundance at the phylum and genus levels in the oral microbiota of the two groups. Results Significant differences in oral microbiota composition were observed between patients in the case and control groups (P

Introduction: Our research aimed to investigate the potential role and mechanism of lysyl oxidase (LOX)-like 2 (LOXL2) in atherosclerosis (AS) by using the human umbilical vein endothelial cells (HUVECs) stimulated by oxidized low-density lipoprotein (ox-LDL). Methods: HUVECs were treated with ox-LDL at different concentrations (0, 10, 25, 50, and 100 μg/mL) and incubated for 24 h. The transfection efficacy of siLOXL2 was investigated by Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). Cell migration, intracellular ROS measurement, oxidative stress, enzyme-linked immunosorbent assay, and adhesion assays were carried out to examine the ox-LDL-induced HUVECs injury. RT-qPCR and Western blot were used to determine gene and protein expression levels. Results: LOXL2 protein expression increased in ox-LDL-induced endothelial cells (ECs). ox-LDL + siLOXL2 significantly inhibited the migration ability of HUVECs and reduced the expression of vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase 9 gene expressions (all, p < 0.05). The ox-LDL + siLOXL2 significantly reduced intracellular ROS production and inhibited the expression of Malondialdehyde, whereas it markedly enhanced superoxide dismutase and catalase (all, p < 0.05). Supernatant levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were significantly attenuated by the ox-LDL + siLOXL2 treatment (all, p < 0.05). ox-LDL + siLOXL2 markedly suppressed the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (all, p < 0.05). ox-LDL + siLOXL2 treatment remarkably reduced the expression of α-smooth muscle actin and vimentin, while increased CD31 and von Willebrand factor gene expression (all, p < 0.05). Conclusion: LOXL2 silencing is protected against ox-LDL-induced EC dysfunction, and the mechanism may be related to the inhibition of the EndMT pathway.

Abstract Background Altered volumes in the hippocampus and amygdala have been linked to anorexia nervosa (AN). This study aimed to investigate amygdala and hippocampal subfields volume abnormalities in AN patients, and their associations with parental rearing practices and clinical psychological characteristics. Methods This study included twenty-nine drug-naive females with AN from West China Hospital of Sichuan University, China, and fifty-nine age- and gender-matched healthy controls (HCs) recruited through advertisement. All participants underwent T1-weighted imaging. Amygdala and hippocampal subfields volume was calculated using FreeSurfer 7.0. The Core Self-Evaluation Scale (CSES) and Rosenberg Self-Esteem Scale (RSES) were used to assess the psychological characteristics of AN patients. The Egna Minnen av Barndoms Uppfostran (EMBU) was employed to evaluate parental rearing practices. Group differences in brain volumes were analyzed with covariates like age and total intracranial volume (TIV). Partial correlation analysis explored the correlations between brain region volumes and clinical psychological characteristics. Results AN patients exhibited lower RSES and CSES scores, and more adverse parental rearing style than healthy norms. After adjusting for covariates, AN patients showed decreased gray matter volume (GMV) in the left medial (Me) and cortical (Co) nucleus, as well as in the right hippocampal-amygdala transition area (HATA). GMV in the left Me was correlated with years of education among HCs but not among AN patients. GMV in the right HATA was positively correlated with paternal penalty and severity, as well as maternal overinterference. Conclusion This study supports structure abnormalities in amygdala and hippocampus in AN patients and suggests that parental rearing practices may be associated with hippocampal abnormalities, potentially contributing to the pathophysiology of AN. Addressing appropriate parental rearing styles may offer a positive impact on AN.

Abstract Background Ferroptosis can be used as a powerful predictor of cancer prognosis. HPV persistent infection is the main cause of cervical cancer, so it is very important to improve the prognosis of patients. Therefore, it is necessary to explore the value of HPV-ferroptosis related genes as prognostic biomarkers of cervical cancer patients. Methods In this study, differentially expressed HPV-ferroptosis related genes were obtained from GSE7410, HPV gene set crossed with iron death genes. Five HPV-ferroptosis related genes with prognostic features were finally identified: CYBB, VEGFA, CKB, EFNA1 and HELLS. Multifactorial Cox regression was applied to establish and validate the prognostic model, and drug susceptibility and immune infiltration analyses were also performed. Results The prognostic model was validated in the training set (TCGA) and validation set (GSE44001). Kaplan–Meier curves reveal significant differences in overall survival (OS) between high-risk and low-risk groups. Receiver operating characteristic (ROC) curve reflects the stability and accuracy of the prognostic model established in this study. In terms of immune function, T cell costimulation was better in the low-risk group than in the high-risk group (P

In the high-level radioactive waste (HLW) deep geological repository, bentonite is compacted uniaxially, and then arranged vertically in engineered barriers. The assembly scheme induces the initial anisotropy, and with hydration, it develops more evidently under chemical conditions. To investigate the anisotropic swelling of compacted Gaomiaozi (GMZ) bentonite and the further response to saline effects, a series of constant-volume swelling pressure tests were performed. Results showed that dry density enhanced the bentonite swelling and raised the final anisotropy, whereas saline inhibited the bentonite swelling but still promoted the final anisotropy. The final anisotropy coefficient (ratio of radial to axial pressure) obeyed the Boltzmann sigmoid attenuation function, decreasing with concentration and dry density, converging to a minimum value of 0.76. The staged evolution of anisotropy coefficient was discovered, that saline inhibited the rise of the anisotropy coefficient (Δδ) in the isotropic process greater than the valley (δ1) in the anisotropic process, leading to the final anisotropy increasing. The isotropic stage amplified the impact of soil structure rearrangement on the macro-swelling pressure values. Thus, a new method for predicting swelling pressures of compacted bentonite was proposed, by expanding the equations of Gouy-Chapman theory with a dissipative wedge term. An evolutionary function was constructed, revealing the correlation between the occurrence time and the pressure value due to the structure rearrangement and the former crystalline swelling. Accordingly, a design reference for dry density was given, based on the chemical conditions around the pre-site in Beishan, China. The anisotropy promoted by saline would cause a greater drop of radial pressure, making the previous threshold on axial swelling fail.

Abstract The combination of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) in the treatment of tumors is emerging as a way to improve ICIs-resistant tumor therapy. In addition, gut microbes (GMs) are involved in angiogenesis in the tumor microenvironment and are also associated with the antitumor function of immune checkpoint inhibitors. However, it is unclear whether gut microbes have a role in anti-tumor function in the combination of anti-angiogenic drugs and immune checkpoint inhibitors for cancer treatment. Endostatin, an angiogenesis inhibitor, has been widely used as an antiangiogenic therapy for cancer. We showed that combined therapy with an adenovirus encoding human endostatin, named Ad-E, and PD-1 blockade dramatically abrogated MC38 tumor growth. The structure of intestinal microbes in mice was changed after combination treatment. We found that the antitumor function of combination therapy was inhibited after the elimination of intestinal microbes. In mice with depleted microbiota, oral gavage of Bacteroides fragilis salvaged the antitumor effects of combination Ad-E and αPD-1 monoclonal antibody (mAb) to a certain extent. Further, Bacteroides fragilis could improve CD3+T cells, NK cells, and IFNγ+CD8+ T cells in the tumor microenvironment to inhibit tumor growth. Besides, Bacteroides fragilis might restore antitumor function by down-regulating isobutyric acid (IBA). Our results suggested that GMs may be involved in the combination of Ad-E and αPD-1 mAb for cancer treatment, which has oncological implications for tumor growth dynamics and cancer immune surveillance.

CO2 conversion is gradually seen as a better way for society to effectively use carbon sources and avoid climate crisis associated with fossil CO2 emissions. And the decision to deploy CO2 technology scale should be relied on its environmental impact. In this work, life cycle assessment model evaluates the environmental performance of CO2 conversion by photocatalytic reaction process with two different catalysts (NiAl-LDH and Co-ZIF-9). Six impact categories considered in this analysis, including climate change, acidification potential, depletion of abiotic resources, eutrophication potential, ozone layer depletion potential, and photochemical oxidation potential. Results indicated that CO2 conversion with Co-ZIF-9 photocatalyst has a better environmental impact than the NiAl-LDH photocatalyst route. Moreover, the Co-ZIF-9 catalyst scenario also has a lower total environmental burden than the conventional CO production route. Sensitivity analysis shows that recycle performance of the catalyst is highly sensitive to the production process in two scenarios. This study could provide a framework for robust decisions in CO2 conversion by photocatalytic reaction, which is useful for policymakers to decide the feasibility of industrialization.

Extrusion-based 3D bioprinting techniques are revolutionizing bioengineering by facilitating the creation of complex 3D microstructures. This review offers a thorough overview of extrusion-based 3D bioprinting methods, particularly highlighting the innovative electric-assisted coil-write 3D bioprinting technology. The review begins by explicating the fundamental principles underlying various extrusion-based 3D bioprinting technologies. It covers the printing equipment composition, suitable materials for 3D bioprinting, and the latest breakthroughs in technology. A critical aspect of this review is the in-depth comparison of the strengths and weaknesses associated with each 3D bioprinting approach. The electro-microfluidic extrusion method and the electric-assisted coil-write 3D bioprinting technology are highlighted. This advanced technology successfully overcomes the limitations of conventional extrusion-based methods, notably in the precise printing of intricately curved line structures with high resolution and speed. This method ingeniously integrates mechanical motion for creating microscale features with electrical coiling for sub-micron details, thus achieving remarkable printing speeds and structural complexity. This review concludes by exploring the potential applications and future advancements of this state-of-the-art technology. It underscores the ability of electric-assisted coil-write 3D bioprinting to develop pioneering materials and micro-devices for a variety of technological sectors, highlighting its transformative impact in bioengineering.

Rare actinomycete genera are highly recognized as a promising source of structurally diverse and bioactive natural products. Among these genera, Allokutzneria and Kibdelosporangium are two phylogenetically closely related and have been reported to encode some valuable biosynthetic enzymes and secondary metabolites. However, there is currently no relevant systematic research available to outline the linkage of genomic and metabolomics for specific secondary metabolites in these two promising genera. In this study, we first investigated the genus-specific secondary metabolic potential in Allokutzneria and Kibdelosporangium by comparing the diversity and novelty of their secondary metabolite biosynthetic gene clusters (BGCs). The specific secondary metabolites produced by two representative strains of these genera were comprehensively investigated using untargeted metabolomics techniques. The findings unveiled that the majority (95.4%) of the gene cluster families (GCFs) encoded by Allokutzneria and Kibdelosporangium were genus-specific, including NRPS GCFs encoding siderophores. The untargeted metabolomics analysis revealed that the metabolic profiles of two representative strains exhibit extensive specificity, with the culture medium having a big impact on the metabolic profiles. Besides, an MS-cluster featuring a series of hydroxamate-type siderophores was identified from Allokutzneria albata JCM 9917, with two of them, including a novel one (N-deoxy arthrobactin A), being experimentally validated. The present study offers valuable insights for the targeted discovery of genus-specific natural products from microorganisms.

Abstract Abnormal cardiac development has been observed in individuals with Cornelia de Lange syndrome (CdLS) due to mutations in genes encoding members of the cohesin complex. However, the precise role of cohesin in heart development remains elusive. In this study, we aimed to elucidate the indispensable role of SMC3, a component of the cohesin complex, in cardiac development and its underlying mechanism. Our investigation revealed that CdLS patients with SMC3 mutations have high rates of congenital heart disease (CHD). We utilized heart-specific Smc3-knockout (SMC3-cKO) mice, which exhibit varying degrees of outflow tract (OFT) abnormalities, to further explore this relationship. Additionally, we identified 16 rare SMC3 variants with potential pathogenicity in individuals with isolated CHD. By employing single-nucleus RNA sequencing and chromosome conformation capture high-throughput genome-wide translocation sequencing, we revealed that Smc3 deletion downregulates the expression of key genes, including Ets2, in OFT cardiac muscle cells by specifically decreasing interactions between super-enhancers (SEs) and promoters. Notably, Ets2-SE-null mice also exhibit delayed OFT development in the heart. Our research revealed a novel role for SMC3 in heart development via the regulation of SE-associated genes, suggesting its potential relevance as a CHD-related gene and providing crucial insights into the molecular basis of cardiac development.

Abstract Drought is a major abiotic stress affecting crop yields. Mapping quantitative trait loci (QTLs) and mining genes for drought tolerance in rice are important for identifying gene functions and targets for molecular breeding. Here, we performed linkage analysis of drought tolerance using a recombinant inbred line population derived from Jileng 1 (drought sensitive) and Milyang 23 (drought tolerant). An ultra-high-density genetic map, previously constructed by our research team using genotype data from whole-genome sequencing, was used in combination with phenotypic data for rice grown under drought stress conditions in the field in 2017–2019. Thirty-nine QTLs related to leaf rolling index and leaf withering degree were identified, and QTLs were found on all chromosomes except chromosomes 6, 10, and 11. qLWD4-1 was detected after 32 days and 46 days of drought stress in 2017 and explained 7.07–8.19% of the phenotypic variation. Two loci, qLRI2-2 and qLWD4-2, were identified after 29, 42, and 57 days of drought stress in 2018. These loci explained 10.59–17.04% and 5.14–5.71% of the phenotypic variation, respectively. There were 281 genes within the QTL interval. Through gene functional annotation and expression analysis, two candidate genes, Os04g0574600 and OsCHR731, were found. Quantitative reverse transcription PCR analysis showed that the expression levels of these genes were significantly higher under drought stress than under normal conditions, indicating positive regulation. Notably, Os04g0574600 was a newly discovered drought tolerance gene. Haplotype analysis showed that the RIL population carried two haplotypes (Hap1 and Hap2) of both genes. Lines carrying Hap2 exhibited significantly or extremely stronger drought tolerance than those carrying Hap1, indicating that Hap2 is an excellent haplotype. Among rice germplasm resources, there were two and three haplotypes of Os04g0574600 and OsCHR731, respectively. A high proportion of local rice resources in Sichuan, Yunnan, Anhui, Guangdong and Fujian provinces had Hap of both genes. In wild rice, 50% of accessions contained Hap1 of Os04g0574600 and 50% carried Hap4; 13.51%, 59.46% and 27.03% of wild rice accessions contained Hap1, Hap2, and Hap3, respectively. Hap2 of Os04g0574600 was found in more indica rice resources than in japonica rice. Therefore, Hap2 has more potential for utilization in future drought tolerance breeding of japonica rice.

ObjectiveThis paper analyzes and models the core logic of a strike chain in terms of time sensitivity, reconfiguration and coverage, thereby providing model and method support for improving the dynamic management ability of naval combat resources under confrontation conditions. MethodsFirst, the typical combat platforms and elements related to the cross-domain cooperative combat of naval battlefields, such as escort ships, UAVs and unmanned boats, are abstracted into four types of resource nodes, namely detection, processing, decision-making and strike. Next, taking the shortest delay as the goal and considering constraints such as wide battlespace, low transmission rate between nodes and limited communication distance, the dynamic integration optimization mathematical model of the strike chain is established. A typical air defense scenario is then designed to demonstrate the shortest delay analysis of the strike chain and the destruction reconstruction analysis under the absence or attack of nodes, and quantitatively describe the changes of the shortest delay and sector coverage index of the reorganized strike chain under countermeasure conditions. Finally, based on a typical combat example of a Ukrainian unmanned cluster attack on the Black Sea Fleet, the ability of the fleet to resist the attack is analyzed on basis of the strike chain model. ResultsThe simulation results show that the model can be used to generate multiple strike chains with the shortest delays, and the responsibility division of each strike chain can be optimized, forming a multi-target killing network at sea. The destruction reconstruction of the strike chain often needs to pay such costs as increased delay and decreased sector coverage. The model can also be used to test anti-saturation attack ability under different formations.ConclusionsThis paper studies and validates the feasibility of analyzing the naval warfare system based on the strike chain model, and can provide theoretical model support for the subsequent design of future naval joint combat systems oriented to the killing network.

As a highly prevalent disease worldwide, diabetes kidney disease （DKD） is a common complication of diabetes and a major cause of end-stage renal disease （ESRD）. One clinical symptom of DKD is persistent proteinuria with or without a gradual decrease in glomerular filtration rate （GFR）. Urinary microalbumin is currently recognized as a marker of early renal injury. However, it has some limitations. Kidney biopsy is a gold diagnostic standard for DKD. Yet its wider applications are restricted by its invasive nature. Therefore actively seeking non-invasive and reliable diagnostic modalities for DKD is of great significance. This review summarized the latest researches of early non-invasive diagnosis of DKD and provided valuable references for an early diagnosis of DKD in clinical practices.

Abstract The realization and control of exchange bias (EB) are highly desirable for spintronic applications. All-oxide heterostructures comprised of ferromagnetic and antiferromagnetic/multiferroic oxides provide an ideal platform to enable the electric-field control of EB, promising for energy-efficient memory and logic devices. However, the low block temperature (TB) and small bias field (HEB) hinder further advances towards room-temperature applications. Here, we report an alternative approach to enhance the interface-induced EB by using ferrimagnetic double-perovskite with B-site cation ordering. In heterostructures comprised of double-perovskite Sr2FeReO6 (SFRO) and LaFeO3 (LFO), a high TB (about 250 K) and large HEB are observed, which is significantly larger than the counterparts with LFO and ferromagnetic oxides. Further analysis suggests that the cation-ordering and ferrimagnetic spin structure of the double-perovskite could contribute significantly to the enhanced exchanged bias when interfacing with G-type antiferromagnets. Our results open a new avenue for developing all-oxides heterostructures for future magnetic technologies.

Abstract Background Extranodal natural killer/T-cell lymphoma (ENKTL) with tonsil involvement is not common, especially in children. Case presentation A 13-year-old girl presented with an unexplained sore throat for more than 2 months, together with intermittent fever and suppurative tonsilitis. Nasopharyngoscopy revealed a pharyngeal mass. Enhanced computed tomography (CT) scan showed tonsillar hypertrophy and punctate calcification. Chronic pyogenic granulomatous inflammation with pseudoepithelial squamous epithelial hyperplasia was observed in left tonsil, and pyogenic granulomatous inflammation and a small number of T-lymphoid cells were detected in the right tonsil. The immunohistochemical results showed CD2+, CD3+, CD4+, CD5+, CD8+, granzyme B+, and TIA-1+. The Ki-67 proliferation index was 20%. The case showed T cell receptor gene rearrangement. Finally, the case was diagnosed as ENKTL of stage II with tonsil involvement. The patient received 6 cycles of chemotherapy with SMILE regimen, and showed complete response with no recurrence in the follow-up. Conclusion We presented a rare case of ENKTL with tonsil involvement in a child. The patient showed complete response to the SMILE chemotherapy with no recurrence.

Abstract Background Endometriosis (EMs) is an enigmatic disease of yet-unknown pathogenesis. Disulfidptosis, a novel identified form of programmed cell death resulting from disulfide stress, stands a chance of treating diverse ailments. However, the potential roles of disulfidptosis-related genes (DRGs) in EMs remain elusive. This study aims to thoroughly explore the key disulfidptosis genes involved in EMs, and probe novel diagnostic markers and candidate therapeutic compounds from the aspect of disulfidptosis based on bioinformatics analysis, machine learning, and animal experiments. Results Enrichment analysis on key module genes and differentially expressed genes (DEGs) of eutopic and ectopic endometrial tissues in EMs suggested that EMs was closely related to disulfidptosis. And then, we obtained 20 and 16 disulfidptosis-related DEGs in eutopic and ectopic endometrial tissue, respectively. The protein-protein interaction (PPI) network revealed complex interactions between genes, and screened nine and ten hub genes in eutopic and ectopic endometrial tissue, respectively. Furthermore, immune infiltration analysis uncovered distinct differences in the immunocyte, human leukocyte antigen (HLA) gene set, and immune checkpoints in the eutopic and ectopic endometrial tissues when compared with health control. Besides, the hub genes mentioned above showed a close correlation with the immune microenvironment of EMs. Furthermore, four machine learning algorithms were applied to screen signature genes in eutopic and ectopic endometrial tissue, including the binary logistic regression (BLR), the least absolute shrinkage and selection operator (LASSO), the support vector machine-recursive feature elimination (SVM-RFE), and the extreme gradient boosting (XGBoost). Model training and hyperparameter tuning were implemented on 80% of the data using a ten-fold cross-validation method, and tested in the testing sets which determined the excellent diagnostic performance of these models by six indicators (Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, Accuracy, and Area Under Curve). And seven eutopic signature genes (ACTB, GYS1, IQGAP1, MYH10, NUBPL, SLC7A11, TLN1) and five ectopic signature genes (CAPZB, CD2AP, MYH10, OXSM, PDLIM1) were finally identified based on machine learning. The independent validation dataset also showed high accuracy of the signature genes (IQGAP1, SLC7A11, CD2AP, MYH10, PDLIM1) in predicting EMs. Moreover, we screened 12 specific compounds for EMs based on ectopic signature genes and the pharmacological impact of tretinoin on signature genes was further verified in the ectopic lesion in the EMs murine model. Conclusion This study verified a close association between disulfidptosis and EMs based on bioinformatics analysis, machine learning, and animal experiments. Further investigation on the biological mechanism of disulfidptosis in EMs is anticipated to yield novel advancements for searching for potential diagnostic biomarkers and revolutionary therapeutic approaches in EMs.

Abstract Background Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients. Methods This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs. Results 92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs. Conclusion Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.

Abstract Magnons, bosonic quasiparticles carrying angular momentum, can flow through insulators for information transmission with minimal power dissipation. However, it remains challenging to develop a magnon-based logic due to the lack of efficient electrical manipulation of magnon transport. Here we show the electric excitation and control of multiferroic magnon modes in a spin-source/multiferroic/ferromagnet structure. We demonstrate that the ferroelectric polarization can electrically modulate the magnon-mediated spin-orbit torque by controlling the non-collinear antiferromagnetic structure in multiferroic bismuth ferrite thin films with coupled antiferromagnetic and ferroelectric orders. In this multiferroic magnon torque device, magnon information is encoded to ferromagnetic bits by the magnon-mediated spin torque. By manipulating the two coupled non-volatile state variables—ferroelectric polarization and magnetization—we further present reconfigurable logic operations in a single device. Our findings highlight the potential of multiferroics for controlling magnon information transport and offer a pathway towards room-temperature voltage-controlled, low-power, scalable magnonics for in-memory computing.

Due to the concentrated carbon emission sources and the enormous carbon emissions in the Ningxia Hui Autonomous, it is necessary to evaluate carbon sequestration potential to support future CCUS planning and major demonstrations. Based on the basic geological conditions for carbon sequestration in Ningxia, this study used the volumetric method of the US Department of Energy (US-DOE) to assess the geological potential for deep saline aquifer sequestration in Ningxia. The results show that the predicted geological potential of carbon sequestration in the deep saline aquifers in Ningxia is approximately 86.742 billion tons, with the predicted technical capacity of about 42.334 billion tons. The main reservoirs are concentrated in the Yanchi area in eastern Ningxia and the Liupan Mountain Basin. A preliminary evaluation of the suitability of saline aquifer sequestration in Ningxia was conducted by considering many factors such as the overall sequestration potential, cap rock integrity, geological stability, and socio-environmental risks. The results indicate that the Yanchi area in eastern Ningxia has favorable reservoir and cap rock conditions, stable structures, and low population density, making it a potential region for CO2 sequestration in Ningxia.

Abstract Ovalbumin (OVA) in egg is one of the predominant causes of food allergy around the world. In the present study, the alleviating effect of selenium‐enriched tea polysaccharide (Se‐TPS) on OVA allergy was evaluated, and the underlying mechanistic insights were investigated. Se‐TPS significantly alleviated the clinical manifestations and diarrhea of allergic mice, accelerated the recovery of jejunal injury, and decreased the immune organ index. Meanwhile, Se‐TPS decreased the levels of immunoglobulin E (IgE), histamine, and IL‐4 in serum, increased the levels of IFN‐γ, and promoted the balance of Th1/Th2 cells. Furthermore, the intervention of Se‐TPS reshaped the gut microbiota structure of OVA‐allergic mice. Se‐TPS increased the abundance of Lachnospiraceae_NK4A136_group, unclassified_f_Lachnospiraceae, and Alistipes, whereas decreased the Faecalibaculum abundance. Analysis of intestinal metabolites showed that Se‐TPS treatment caused a significant increase in homocitrulline and 7a‐hydroxyandrost‐4‐ene‐3,17‐dione levels. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment results indicated that Se‐TPS treatment may alleviate allergic symptoms by enhancing the anti‐inflammatory ability of OVA‐allergic mice through neuroimmunity.

Purpose: This study aimed to identify the altered pathways and genes associated with freezing damage in human sperm during cryopreservation by multiomics analysis. Materials and Methods: Fifteen fresh human semen samples were collected for transcriptomic analysis, and another 5 fresh human semen samples were obtained for metabolomic analysis. For each semen sample, 1 mL was cryopreserved, and another 1 mL was left untreated for paired design. The results were then combined with previously published proteomic results to identify key genes/pathways. Results: Cryopreservation significantly reduced sperm motility and mitochondrial structure. Transcriptomic analysis revealed altered mitochondrial function, including changes in tRNA-methyltransferase activity and adenosine tri-phosphate/adenosine di-phosphate transmembrane transporter activity. Metabolomic analysis showed that the citrate cycle in mitochondria was significantly altered. Combining transcriptomic, proteomic, and metabolomic analyses revealed 346 genes that were altered in at least two omics analyses. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that metabolic pathways were significantly altered and strongly associated with mitochondria. Five genes were altered in all three omics analyses: COL11A1, COL18A1, LPCAT3, NME1, and NNT. Conclusions: Five genes were identified by multiomics analysis in human cryopreserved sperm. These genes might have specific functions in cryopreservation. Explorations of the functions of these genes will be helpful for sperm cryopreservation and sperm motility improvement or even for reproduction in the future.

Direct incorporation of straw into the flooded paddy has been widely confirmed to induce substantial methane (CH4) emissions. Exploring innovative modes of straw return and associated field water management is necessary to mitigate CH4 emissions without compromising crop yield. Here, a 2-year field experiment was conducted with two wheat straw returning modes [straw evenly-plowed returning (SR) with conventional flooding water management, and straw centralized returning (SCR) under rainfed conditions], to evaluate greenhouse gas (GHG) emissions, crop yields, carbon footprint (CF), and net ecosystem economic benefit (NEEB) in the rice-wheat rotation system. The results showed that the GHG emissions contributed significantly to the total annual carbon source value, accounting for 48.0 % and 43.0 % in SR and SCR, respectively. The mean CF in SCR was 6760 kg CO2-eq ha–1, which was 17.6 % lower than that in SR, primarily due to the significantly lower CH4 (by 27.5 %) during the rice seasons. Lower soil water contents might partly regulate the CH4 emissions by decreasing DOC contents and increasing the soil Eh, leading to a lower CH4 production potential (decreased by 44.3–45.8 %) and production/oxidation potential ratio in SCR. Annually, the total yields of rice and wheat were 9.53 t ha–1 and 9.38 t ha–1 in SR and SCR, respectively. However, the irrigation electricity consumption and CF costs were lower in SCR, resulting in an increased NEEB of 179 CNY ha–1 relative to SR. The findings suggest that straw centralized returning under rainfed conditions in the rice season could reduce both CH4 emissions and carbon footprint while sustaining food security and economic benefit in the rice-wheat rotation system.

ObjectiveThe aim of this study was to assess the clinical value of metagenomic next-generation sequencing (mNGS) of blood samples for the identification of disseminated tuberculosis (DTB).MethodsA total of 48 individuals suspected of DTB were enrolled. All patients underwent mNGS of peripheral blood and conventional microbiological tests. Patient characteristics were collected from their medical records.ResultsA total of 28 patients were diagnosed with DTB, whereas 20 patients were confirmed as non-DTB cases. In the DTB groups, 19 (67.9%) contained TB sequences, with specific reads of TB ranging from 1 to 219. The TB sequence was more detectable by mNGS in male patients, those with elevated PCT levels, those who are HIV positive, and those with a decreased CD4 T-cell count. The HIV-positive group shows higher TB mNGS reads (p = 0.012) and TB mNGS sensitivity (p = 0.05). The sensitivity of TB mNGS in blood samples was 80% for HIV-infected patients and 44.4% for non-HIV-infected individuals (p = 0.05). The non-HIV group had a higher prevalence of miliary tuberculosis (p = 0.018), and extrapulmonary tuberculosis was more prevalent in the HIV-positive group.ConclusionOur research has shown that the mNGS of blood samples has excellent sensitivity for the diagnosis of DTB. The TB sequence was more detectable by mNGS in patients with elevated PCT levels, those who are HIV positive, and those with a decreased CD4 T-cell count.

Neurodegenerative diseases (NDDs) represent a category of serious illnesses characterized by the progressive deterioration of neuronal structure and function. The exploration of natural compounds as potential therapeutic agents has gained increasing attention in recent years owing to their wide range of pharmacological activities and minimal side effects. Baicalin (BAI) and baicalein (BE), polyphenolic flavonoids, derived from the root of Scutellaria baicalensis, evidently show potential in treating NDDs. This review provides an overview of the current understanding of the roles of BAI and BE in alleviating neuroinflammation, a pivotal pathological process implicated in various NDDs. Studies conducted prior to clinical trials have shown that BAI and BE exert protective effects on the nervous system in different animal models of NDDs. Furthermore, mechanistic studies indicate that BAI and BE exert anti-inflammatory effects by inhibiting pro-inflammatory cytokines, suppressing microglial activation, and regulating microglial phenotypes. These effects are mediated through the modulation of inflammatory signaling cascades, including Toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), amp-activated protein kinase (AMPK), NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome, and nuclear factor erythroid 2-related factor 2 (Nrf2)/hemoglobin oxygenase-1 (HO-1). Overall, BAI and BE exhibit promising potential as natural compounds with anti-inflammatory properties and offer innovative therapeutic approaches for managing NDDs.

The rapid evolution of high-throughput mass spectrometry (HT-MS) technologies has positioned MS as a pivotal analytical tool across diverse disciplines. Its significance is particularly pronounced in high-throughput drug discovery and development, where MS plays a critical role throughout various phases. Acoustic ejection mass spectrometry (AEMS) is a recent addition to the HT-MS landscape, showcasing a balanced performance high analytical throughput and high data quality. Particularly, AEMS's in-line dilution feature allows the direct analysis of large-scale, complex reaction solutions without the need for sample cleanup, making it a popular choice for large-scale high-throughput screenings. However, the substantial volume of complex matrix introduces concerns about system robustness, specifically regarding the potential clogging of the sample transfer line. This study addresses this challenge by introducing an integrated automatic washing feature to the AEMS system. This enhancement significantly improves system robustness without imposing any additional demands on assay execution time. Demonstrating an extended electrode lifetime, the cleaning approach proves effective in maintaining system performance over prolonged periods, showcasing its potential for continuous large-sample-scale high-throughput analysis applications.

Summary: Cervical lesions pose a significant threat to women’s health worldwide. Colposcopy is essential for screening and treating cervical lesions, but its effectiveness depends on the doctor’s experience. Artificial intelligence-based solutions via colposcopy images have shown great potential in cervical lesions screening. However, some challenges still need to be addressed, such as low algorithm performance and lack of high-quality multi-modal datasets. Here, we established a multi-modal colposcopy dataset of 2,273 HPV+ patients, comprising original colposcopy images, acetic acid reactions at 60s and 120s, iodine staining, diagnostic reports, and pathological results. Utilizing this dataset, we developed CerviFusionNet, a hybrid architecture that merges convolutional neural networks and vision transformers to learn robust representations. We designed a temporal module to capture dynamic changes in acetic acid sequences, which can boost the model performance without sacrificing inference speed. Compared with several existing methods, CerviFusionNet demonstrated excellent accuracy and efficiency.

We investigated the effect of different fat sources on growth performance and intestinal health in weaned piglets. A total of 72 21-day-old weaned piglets were divided into 3 groups the CON group with 2.5% soybean oil, TRE1 with 2.5% emulsified balanced oil powder and TRE2 with 2.5% emulsified coconut oil powder. These two experimental oil powders were emulsified with the emulsifier (lysophospholipid). The average daily feed intake in TRE1 was significantly higher than that in CON (P < 0.05). The apparent total tract digestibility (ATTD) of ash in TRE1 was significantly higher than that in CON (P < 0.05). Compared with CON, TRE1 tended to improve ATTD of dry matter (P = 0.075), serum triglyceride (P = 0.062) and serum-free fatty acids (P = 0.090). The jejunal villus width of piglets in TRE1 and TRE2 was significantly increased (P < 0.05) and the duodenal crypt depth was significantly decreased (P < 0.05). Compared with CON, TRE1 significantly increased the mRNA expression levels of jejunal Occludin, Claudin-1 and ZO-1 (P < 0.05). From the results of the present study, we concluded that dietary supplementation of 2.5% emulsified balanced oil powder has more obvious effects on enhancing the growth performance of weaned piglets by improving lipid metabolism, intestinal tissue development and barrier function.

AbstractMyeloid neoplasms post cytotoxic therapy (MN-pCT) are a category includes AML, MDS, and MDS/MPN arising in patients exposed to cytotoxic (DNA-damaging) therapy for an unrelated condition in 2022 version World Health Organization (WHO) classification. With improved survival of patients with tumors, the incidence of MN-pCT after chemotherapy and/or radiation therapy among patients with tumors has gradually risen. However, the outcome of MN-pCT is poorer than that of primary myeloid neoplasms. This review summarizes the current understanding based on existing research, as a foundation for further research on MN-pCT.

The significant economic losses caused by S. abortus equi in donkey husbandry have increased interest in exploring the potential of phages and their enzymes as control strategies. In this study, a S. abortus equi phage, designated 4FS1, was isolated from sewage at a donkey farm. Transmission electron microscopy (TEM) revealed a typical icosahedral head and a long, non-contractile tail. It exhibited a short latent period of 20 min and a burst size of 160 plaque-forming units (PFU) per cell. It demonstrated a broad host range, infecting 36 out of 60 salmonella strains, with an optimal multiplicity of infection (MOI) of 0.01 for S. abortus equi S1. The phage titer remained stable at 109 PFU/mL between 37°C and 50°C and exceeded 108 PFU/mL at pH from 5.0 to 10.0. After 1 h of UV exposure, the titer remained at 107 PFU/mL and showed no significant variation across NaCl concentrations from 2.5 to 15%. The genome of phage 4FS1 consists of a 42,485 bp linear double-stranded DNA molecule with a G + C content of 49.07%. Of the 56 predicted open reading frames (ORFs), 32 were functional annotated, with no virulence or drug resistance genes identified. ORF36 was predicted to encode a depolymerase responsible for endorhamnosidase activity. Recombinant expression of the Dpo36 protein in prokaryotes significantly reduced biofilm formation and removal. Combined with healthy donkey serum, Dpo36 inhibited bacterial growth in vitro and enhanced the survival rates of mice infected with S. abortus equi. These findings highlight the promising potential of phages and their depolymerases as novel therapeutic agents against S. abortus equi.

IntroductionAlterations in life forms could simultaneously influence the variability of fine root and leaf traits. However, our understanding of the organ-level coordination and patterns of variation in fine root and leaf traits among desert herbs and shrubs with distinct habits remains limited.MethodsConsequently, this study examined the leaf and fine root traits of 9 shrubs and 9 herbs across three desert habitats through Sperman's correlation analysis, principal component analysis (PCA), and standardized major axis (SMA) analysis as a means of identifying the hub traits and the resource trade-off strategies employed by desert plants to adapt to their environment.ResultsThe results showed that the extent of coordination between leaf and root traits, defined as similarity, was contingent upon the life form. While the traits in shrubs were completely decoupled, those in herbs exhibited a high degree of coordination. The traits related to water acquisition and storage are highly connected and do not depend on traits and life forms. Most leaves and fine roots were primarily loaded along the PC1 and PC2 axes of principal component analysis.DiscussionSuggesting that herbs and shrubs each adopt the most advantageous trait syndrome in accordance with their life form to acquire and conserve resources. The leaf economic spectrum and the root economic spectrum evolved independently, showing no dependence on the variations in life form. In conclusion, in desert plants, leaf and root variations occur independently along two axes, with traits associated with water acquisition playing a neutral role in their ecological strategy.

Insomnia is the most common sleep disorder in which an individual has trouble falling or staying asleep. Chronic sleep loss interferes with daily functioning and adversely affects health. The main clinical drugs for insomnia are the positive allosteric modulator of the GABA (gamma-aminobutyric acid) A receptors (GABAARs) at the benzodiazepine site with selectivity of the GABA-α1 receptor. They are divided into benzodiazepine drugs and non-benzodiazepine drugs. Most recently, the first partial positive allosteric modulator of GABAAR Dimdazenil was approved by National Medical Products Administration (NMPA) and launched in China. This review summarized the mechanism of actions of current clinical drugs for insomnia, and the clinical applications of these drugs, which may help to understand their involvement in insomnia, and to search for more selective and potent ligands to be used in the treatment of insomnia.

Purpose: This study aims to address therapy-related toxicities and quality of life in prostate cancer patients undergoing transperineal ultrasound (TPUS) guided radiotherapy (RT). Methods: Acute and late gastrointestinal (GI) and genitourinary (GU) toxicities were assessed by physicians using CTCAE v5.0. Patient-reported quality of life outcomes were evaluated using EORTC QLQ-C30, -PR25 and IPSS. We utilized Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) as the RT technique for this study. The assessments were carried out before RT, at RT end, 3 months after RT and subsequently at 1-year intervals. Prostate-specific antigen (PSA) was also evaluated at each follow-up. Results: In this study, a total of 164 patients were enrolled, while among them, 112 patients delivered quality-of-life data in a prospective evaluation. The median pre-treatment PSA was 7.9 ng/mL (range: 1.8–169 ng/ml). At the median follow-up of 19 months (3–82 months), the median PSA decreased to 0.22 ng/ml. Acute grade II GI and GU toxicities occurred in 8.6 % and 21.5 % patients at RT end. Regarding late toxicities, 2.2 % patients experienced grade II GI toxicities at 27 months and only one patient at 51 months, whereas no grade II GU late toxicities were reported at these time points. Quality of life scores also indicated a well-tolerated treatment. Patients mainly experienced acute clinically relevant symptoms of fatigue, pain, as well as deterioration in bowel and urinary symptoms. However, most symptoms normalized at 3 months and remained stable thereafter. Overall functioning showed a similar decline at RT end but improved over time. Conclusion: The outcomes of TPUS-guided RT demonstrated promising results in terms of minimal physician-reported toxicities and satisfactory patient-reported QoL.

Summary: Extrachromosomal circular DNAs (eccDNAs) are defined as distinct genomic entities of circular and mobile DNA molecules, but their molecular functions in and impact on breast cancer (BC) are rarely known. This study used Circle-seq to analyze eccDNAs from 19 BC tissues and 17 adjacent normal tissues. We found that eccDNAs are present on all chromosomes and enriched in seven eccDNA hotspot genes (HSGs) associated with the BC pathway. Several eccDNAs harboring entire genes (eccGenes) and eccDNAs harboring miRNAs (eccMIRs) were identified and linked to cancer-relevant pathways. Synthetic eccMIR6748, eccMIR6508, and eccMIR3142 elevated miRNA expression in MCF-7 cells, with eccMIR6748 promoting BC cell migration and invasion by upregulating miR-6748, which suppresses tumor suppressor candidate factor 5 (TUSC5) at the post-transcriptional level. eccMIR6748 also influences BC progression via the p38 mitogen-activated protein kinase (MAPK) signaling pathway. These findings suggest that eccDNAs, which contain functional genomic segments, play a role in BC initiation and progression, offering a dynamic source of genomic plasticity and potential as biomarkers and therapeutic targets.

Abstract Aim To identify subtypes of job crafting among Chinese nurses and to explore the characteristics of different subtypes and their relationship with work engagement. Design A cross‐sectional study. Methods A survey of 350 clinical nurses was conducted between December 2022 and January 2023. Identify profile categories for nurses' job crafting using a latent profile analysis. Logistic regression and ANOVA were used to explore the characteristics of different categories of nurses' job crafting in terms of sociodemographic, work engagement variables. Results Ultimately 3 latent profiles are identified: low job crafting (Class 1, N = 177, 50.7%), moderate job crafting (Class 2, N = 136, 38.9%), high job crafting (Class 3, N = 37, 10.5%). Nurses who are female, aged 31 to 40 and married are more likely to be grouped into Class 2. Nurses with a middle level of title are more likely to be grouped as Class 3. Nurses with high levels of work engagement are more likely to be grouped as Class 2 and Class 3 rather than Class 1. Conclusion The job crafting has a distinctly classified character among Chinese nurses. 89.6% of nurses were at a low to medium level of job crafting, work engagement is an important predictor of nurses' job crafting. Nursing Managers should focus on the low job crafting group and develop targeted interventions to help nurses improve their job crafting and work engagement levels. Patient or Public Contribution None.

PurposeCoinfections or consecutive infections of Mucor and Aspergillus are exceedingly uncommon in children, we report the case to offer the valuable experience for colleagues facing similar situations.Case reportThis report documents the first recorded case of successful treatment for pulmonary mixed infection in a diabetic girl. Initially, the patient underwent treatment based on voriconazole, but the infection continued to deteriorate. Subsequently, bronchoalveolar lavage fluid culture and metagenomic next-generation sequencing (mNGS) were conducted, leading to a clear diagnosis of simultaneous infection by Aspergillus fumigatus and Rhizopus microsporus. Susceptibility testing revealed fungal resistance to voriconazole. Therefore, a combined treatment regimen of AmB liposomes and isavuconazole effectively eradicated the fungal infection.ConclusionThis case underscores the importance of early and precise identification of fungal pathogens, determination of effective antifungal medications, and timely implementation of well-planned therapeutic strategies. Furthermore, we comprehensively reviewed 10 cases of pulmonary mixed infections involving Mucor and Aspergillus, summarizing their characteristics and identifying commonalities.