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Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder accompanied by ovulatory dysfunction. Insulin resistance (IR) is a key pathogenic mechanism in PCOS, and insulin sensitizers, such as metformin and pioglitazone, can improve PCOS symptoms. Chiglitazar, a pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, is also an insulin sensitizer; however, its therapeutic effects have not yet been studied in PCOS. We evaluated the therapeutic effects of chiglitazar in a rat model of PCOS. Methods Sprague–Dawley rats aged 4 weeks were injected subcutaneously with dehydroepiandrosterone (DHEA) (6 mg/100 g/day) to establish PCOS, and a control (CON) group was established. The rats were divided into the CON, PCOS model (DHEA), pioglitazone-treated (DHEA + PIO), and chiglitazar-treated (DHEA + CHI) groups. The DHEA + PIO group received pioglitazone (20 mg/kg/day) and the DHEA + CHI group received chiglitazar (20 mg/kg/day), each for 15 days. Body weight, estrous cycle, and glucose tolerance test (GTT) and insulin resistance test (ITT) results were monitored. Experimental animal energy metabolism systems were utilized to assess metabolic parameters. Enzyme-linked immunosorbent assay was conducted to detect changes in serum hormones, including insulin, adiponectin, sex-related hormones, and lipid metabolism indicators. The ovaries were used for molecular biology experiments to detect changes in Akt/phosphorylated Akt and glucose transporter 4 (GLUT4) expression by Western blotting and quantitative polymerase chain reaction. Results Chiglitazar and pioglitazone improved PCOS symptoms. However, chiglitazar demonstrated a more pronounced effect on lipid improvement and weight gain than pioglitazone. In the DHEA + PIO and DHEA + CHI groups, there was notable recovery in oxygen consumption and carbon dioxide output; substantial improvement in GTT and ITT results; an increase in adiponectin; and a reduction in serum insulin, androgens, luteinizing hormone (LH), and LH/follicle-stimulating hormone ratio. Compared with the DHEA group, the DHEA + CHI group exhibited notable decreases in triglycerides, free fatty acids, and atherosclerosis index, while the DHEA + PIO group demonstrated no changes. Granulosa cells and healthy follicles increased in ovarian sections. Ovarian steroidogenic enzymes also increased in the DHEA + PIO and DHEA + CHI groups compared with the DHEA group. Mechanistically, chiglitazar increased Akt phosphorylation. Conclusion Chiglitazar significantly improved ovulation in rats with PCOS and may be a potential novel therapeutic strategy for PCOS.

Abstract Human genetics analysis has identified many noncoding SNPs associated with diabetic traits, but whether and how these variants contribute to diabetes is largely unknown. Here, we focus on a noncoding variant, rs6048205, and report that the risk-G variant impairs the generation of PDX1+/NKX6-1+ pancreatic progenitor cells and further results in the abnormal decrease of functional β cells during pancreatic differentiation. Mechanistically, this risk-G variant greatly enhances RXRA binding and over-activates FOXA2 transcription, specifically in the pancreatic progenitor stage, which in turn represses NKX6-1 expression. Consistently, inducible FOXA2 overexpression could phenocopy the differentiation defect. More importantly, mice carrying risk-G exhibit abnormal pancreatic islet architecture and are more sensitive to streptozotocin or a high-fat diet to develop into diabetes eventually. This study not only identifies a causal noncoding variant in diabetes susceptibility but also dissects the underlying gain-of-function mechanism by recruiting stage-specific factors.

Abstract Prostate cancer is a malignant tumor of the male urological system with the highest incidence rate in the world, which seriously threatens the life and health of middle-aged and elderly men. The progression of prostate cancer involves the interaction between tumor cells and tumor microenvironment. Understanding the mechanisms of prostate cancer pathogenesis and disease progression is important to guide diagnosis and therapy. The emergence of single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (ST-seq) technologies has brought breakthroughs in the study of prostate cancer. It makes up for the defects of traditional techniques such as fluorescence-activated cell sorting that are difficult to elucidate cell-specific gene expression. This review summarized the heterogeneity and functional changes of prostate cancer and tumor microenvironment revealed by scRNA-seq and ST-seq, aims to provide a reference for the optimal diagnosis and treatment of prostate cancer.

Objective To study the RHD genotyping of primary screening RhD negative population in Beijing, and analyze the serological characteristics of different genotypes and the distribution of Rh phenotypes. Methods From August 2022 to January 2024, 204 RhD negative samples in our hospital were initially screened by microplate or microcolumn agglutination method. RhD antigen phenotype was identified by saline tube method, and RhD negative confirmation test was performed by microcolumn gel-indirect antiglobulin technology.RHD genotyping was performed by polymerasing chain reaction-sequence specific primmer (PCR-SSP) method and sequencing technology, and the phenotypic frequency and gene frequency were calculated. Results The distribution of Rh serologic phenotypes in 204 RhD negative samples were 112 cases of ccee (54.90%) > 73 cases of Ccee (35.78%) > 9 cases of CCee (4.41%) > 6 cases of ccEe (2.94%) > 4 cases of CcEe (1.96%). A total of 7 RHD genotypes were detected in this study, including 129 cases of RHD* 01N.01 (63.24%), 44 cases of RHD* 01EL.01 (21.57%), 26 cases of RHD* 01N.03 (12.75%), 2 cases of RHD* 01N.16 (0.98%), 1 case of RHD* 06.03.01 (0.49%), 1 case of weak RHD* 15 (0.49%) and 1 case of RHD* 13.01/RHD* 01N.01 (0.49%). The frequency and phenotype distribution of Rh blood group antigen gene were consistent with Hardy-Weinberg equilibrium (P>0.05). Conclusion The RHD gene is polymorphic in the primary screening RhD negative population in Beijing, and the most common RhD negative genotype is RHD* 01N.01, and the RHD variant is RHD* 01EL.01.This study may provide data to support the clinical implementation of genotype-matched blood transfusions.

Abstract Background Depression is prevalent among lung cancer patients undergoing chemotherapy, and the symptom cluster of fatigue-pain-insomnia may influence their depression. Identifying characteristics of patients with different depression trajectories can aid in developing more targeted interventions. This study aimed to identify the trajectories of depression and the fatigue-pain-insomnia symptom cluster, and to explore the predictive factors associated with the categories of depression trajectories. Methods In this longitudinal study, 187 lung cancer patients who were undergoing chemotherapy were recruited and assessed at the first (T1), second(T2), and fourth(T3) months using the Patient Health Questionnaire-9 (PHQ-9), the Brief Pain Inventory (BPI), the Brief Fatigue Inventory (BFI), and the Athens Insomnia Scale (AIS). Growth Mixture Model (GMM) and Latent Class Analysis (LCA) were used to identify the different trajectories of the fatigue-pain-insomnia symptom cluster and depression. Binary logistic regression was utilized to analyze the predictive factors of different depressive trajectories. Results GMM identified two depressive trajectories: a high decreasing depression trajectory (40.64%) and a low increasing depression trajectory (59.36%). LCA showed that 48.66% of patients were likely members of the high symptom cluster trajectory. Binary logistic regression analysis indicated that having a history of alcohol consumption, a higher symptom cluster burden, unemployed, and a lower monthly income predicted a high decreasing depression trajectory. Conclusions Depression and fatigue-pain-insomnia symptom cluster in lung cancer chemotherapy patients exhibited two distinct trajectories. When managing depression in these patients, it is recommended to strengthen symptom management and pay particular attention to individuals with a history of alcohol consumption, unemployed, and a lower monthly income.

Abstract With the changing times, obesity has become a characteristic epidemic in the context of the current era. Insulin resistance (IR) is most commonly caused by obesity, and IR is a common basis of the pathogenesis of many diseases such as cardiovascular disease, nonalcoholic fatty liver disease, and type 2 diabetes, which seriously threaten human life, as well as health. A major pathogenetic mechanism of obesity-associated IR has been found to be chronic low-grade inflammation in adipose tissue. Specialized pro-resolving mediators (SPMs) are novel lipid mediators that both function as “stop signals” for inflammatory reaction and promote inflammation to subside. In this article, we summarize the pathogenesis of obesity-associated IR and its treatments and outline the classification and biosynthesis of SPMs and their mechanisms and roles in the treatment of obesity-associated IR in order to explore the potential of SPMs for treating metabolic diseases linked with obesity-associated IR.

Abstract Introduction D–Phenotype is linked to abnormal expression of RHCE gene. Consequently, individuals with this condition may develop antibodies against high-prevalence Rh antigens when exposed to a normal Rh phenotype, leading to challenges in blood matching. Case presentation A 90-year-old male was admitted to the hospital due to prostatitis and acute retention of urinary. Surgery was planned after evaluation by urologist. A request was made for 2 units of red blood cells (RBC). The result for unexpected antibody screening was positive, and the antibody was identified as anti-Hr0 alloantibody , a rare RHCE * CE-D (5) – CE was discovered by genetic testing. The patient has only one history of blood transfusion, which may result in the production of the anti-Hr0 antibody. Compatible blood donors for this patient were not found, even after extensive screening. Conclusion This report records a rare case of a D-- phenotype individual who produced anti-Hr0 alloantibody. Subsequent analysis of RH gene sequencing revealed a genotype that has not been previously reported in Asia.

Abstract Background The senescence of renal tubular epithelial cells (RTECs) is crucial in the progression of diabetic kidney disease (DKD). Accumulating evidence suggests a close association between insufficient mitophagy and RTEC senescence. Yeast mitochondrial escape 1-like 1 (YME1L), an inner mitochondrial membrane metalloprotease, maintains mitochondrial integrity. Its functions in DKD remain unclear. Here, we investigated whether YME1L can prevent the progression of DKD by regulating mitophagy and cellular senescence. Methods We analyzed YME1L expression in renal tubules of DKD patients and mice, explored transcriptomic changes associated with YME1L overexpression in RTECs, and assessed its impact on RTEC senescence and renal dysfunction using an HFD/STZ-induced DKD mouse model. Tubule-specific overexpression of YME1L was achieved through the use of recombinant adeno-associated virus 2/9 (rAAV 2/9). We conducted both in vivo and in vitro experiments to evaluate the effects of YME1L overexpression on mitophagy and mitochondrial function. Furthermore, we performed LC–MS/MS analysis to identify potential protein interactions involving YME1L and elucidate the underlying mechanisms. Results Our findings revealed a significant decrease in YME1L expression in the renal tubules of DKD patients and mice. However, tubule-specific overexpression of YME1L significantly alleviated RTEC senescence and renal dysfunction in the HFD/STZ-induced DKD mouse model. Moreover, YME1L overexpression exhibited positive effects on enhancing mitophagy and improving mitochondrial function both in vivo and in vitro. Mechanistically, our LC–MS/MS analysis uncovered a crucial mitophagy receptor, BCL2-like 13 (BCL2L13), as an interacting partner of YME1L. Furthermore, YME1L was found to promote the phosphorylation of BCL2L13, highlighting its role in regulating mitophagy. Conclusions This study provides compelling evidence that YME1L plays a critical role in protecting RTECs from cellular senescence and impeding the progression of DKD. Overexpression of YME1L demonstrated significant therapeutic potential by ameliorating both RTEC senescence and renal dysfunction in the DKD mice. Moreover, our findings indicate that YME1L enhances mitophagy and improves mitochondrial function, potentially through its interaction with BCL2L13 and subsequent phosphorylation. These novel insights into the protective mechanisms of YME1L offer a promising strategy for developing therapies targeting DKD.

Abstract Background Diabetic peripheral neuropathy (DPN) is a prevalent and serious complication of diabetes mellitus, impacting the nerves in the limbs and leading to symptoms like pain, numbness, and diminished function. While the exact molecular and immune mechanisms underlying DPN remain incompletely understood, recent findings indicate that mitochondrial dysfunction may play a role in the advancement of this diabetic condition. Methods Two RNA transcriptome datasets (codes: GSE185011 and GSE95849), comprising samples from diabetic peripheral neuropathy (DPN) patients and healthy controls (HC), were retrieved from the Gene Expression Omnibus (GEO) database hosted by the National Center for Biotechnology Information (NCBI). Subsequently, differential expression analysis and gene set enrichment analysis were performed. Protein–protein interaction (PPI) networks were constructed to pinpoint key hub genes associated with DPN, with a specific emphasis on genes related to mitochondria and peripheral neuropathy disease (PND) that displayed differential expression. Additionally, the study estimated the levels of immune cell infiltration in both the HC and DPN samples. To validate the findings, quantitative polymerase chain reaction (qPCR) was employed to confirm the differential expression of selected genes in the DPN samples. Results This research identifies four hub genes associated mitochondria or PN. Furthermore, the analysis revealed increased immune cell infiltration in DPN tissues, particularly notable for macrophages and T cells. Additionally, our investigation identified potential drug candidates capable of regulating the expression of the four hub genes. These findings were corroborated by qPCR results, reinforcing the credibility of our bioinformatics analysis. Conclusions This study provides a comprehensive overview of the molecular and immunological characteristics of DPN, based on both bioinformatics and experimental methods.

ChatGPT, a generative pretrained transformer, has garnered global attention and sparked discussions since its introduction on November 30, 2022. However, it has generated controversy within the realms of medical education and scientific research. This paper examines the potential applications, limitations, and strategies for using ChatGPT. ChatGPT offers personalized learning support to medical students through its robust natural language generation capabilities, enabling it to furnish answers. Moreover, it has demonstrated significant use in simulating clinical scenarios, facilitating teaching and learning processes, and revitalizing medical education. Nonetheless, numerous challenges accompany these advancements. In the context of education, it is of paramount importance to prevent excessive reliance on ChatGPT and combat academic plagiarism. Likewise, in the field of medicine, it is vital to guarantee the timeliness, accuracy, and reliability of content generated by ChatGPT. Concurrently, ethical challenges and concerns regarding information security arise. In light of these challenges, this paper proposes targeted strategies for addressing them. First, the risk of overreliance on ChatGPT and academic plagiarism must be mitigated through ideological education, fostering comprehensive competencies, and implementing diverse evaluation criteria. The integration of contemporary pedagogical methodologies in conjunction with the use of ChatGPT serves to enhance the overall quality of medical education. To enhance the professionalism and reliability of the generated content, it is recommended to implement measures to optimize ChatGPT’s training data professionally and enhance the transparency of the generation process. This ensures that the generated content is aligned with the most recent standards of medical practice. Moreover, the enhancement of value alignment and the establishment of pertinent legislation or codes of practice address ethical concerns, including those pertaining to algorithmic discrimination, the allocation of medical responsibility, privacy, and security. In conclusion, while ChatGPT presents significant potential in medical education, it also encounters various challenges. Through comprehensive research and the implementation of suitable strategies, it is anticipated that ChatGPT’s positive impact on medical education will be harnessed, laying the groundwork for advancing the discipline and fostering the development of high-caliber medical professionals.

Adjuvant chemoradiotherapy, molecular targeted therapy, and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer (GC). However, most of these treatments have toxic side effects, drug resistance, and limited improvements in survival and quality of life. Therefore, it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity. In previous studies, the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity; however, the specific mechanism was unclear. Our research utilising co-immunoprecipitation-mass spectrometry (Co-IP-MS), polypyrimidine tract binding protein 1 (ptbp1) clustered regularly interspaced short palindromic repeat-associated protein 9 (Cas9)-knockout (KO) mouse model, tissue microarray, and functional experiments suggests that alpha actinin-4 (ACTN4) could be a significant biomarker of GC. PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4. Celastrus orbiculatus stem extract (COE) may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4, thereby exerting anti-GC effects.

Mysids have become the preferred diet for Sepia and Hippocampus breeding due to their nutritional content and size. Despite their potential as a high-quality feed, limited literature exists on the specific nutritional needs of N. orientalis and how diet influences their reproduction. This study investigated the effects of various diets—Corethron sp., Chlorella sp., mixed algae, and flakes—on the survival, total reproductive output, and whole tissue nutritional composition of N. orientalis. The main results were as follows: 1) N. orientalis fed with Corethron sp. exhibited the highest survival (90.11 ± 5.09% at 14 d; 57.78 ± 5.09% at 21 d); 2) Significant differences in total reproductive output were observed among the dietary groups, with the mixed diet group showing the highest output (121.67 ± 5.03 ind), followed by the Corethron sp. group (102.67 ± 3.51 ind); 3) Principal component analysis revealed that the nutritional composition of mysids predominantly comprises C18:2n-6, C22:6n-3, Σn-3 PUFA, Asp, Glu, Val, Phe, and TAA; 4) Correlation analysis indicated a strong positive correlation between the dietary C18:2n-6 and Σn-3 PUFA and the survival and total reproductive output of N. orientalis. Additionally, the dietary C20:4n-6 and C20:5n-3 showed a strong positive correlation with the C22:5n-3 and Σn-3 PUFA in N. orientalis. A similar strong positive correlation was observed between dietary amino acids and those in mysids. In conclusion, the study demonstrates that different diets directly influence the nutritional composition of mysids, affecting their survival and total reproductive output during the breeding period. Consequently, Corethron sp. emerges as a suitable diet for N. orientalis, enriching C20:5n-3 and Σn-3 PUFA, which fulfills the nutritional requirements of N. orientalis during their reproductive period, thereby enhancing individual survival and reproduction.

This study examined the applicability of indocyanine green (ICG) fluorescence imaging to assist the laparoscopic resection of retroperitoneal tumors in pediatric patients via an abdominal approach. Conducted prospectively at the Guangzhou Women and Children's Medical Center from May to September 2023, the research included three pediatric cases, for whom laparoscopic retroperitoneal tumor resections were performed utilizing ICG fluorescence imaging. In each case, ICG was intravenously administered (0.3 mg/kg) prior to surgery, enabling the visualization of vital vascular structures through real-time fluorescence imaging. The trocar's placement was guided by a “four-hole” technique from the healthy side in a 70-degree lateral decubitus position. The operations were accomplished successfully without any complications. Pathological analysis of the patients identified one case of Wilms tumor of the embryonal type, one ganglioneuroblastoma of the mature type without N-MYC gene amplification, and one mature cystic teratoma. The findings suggest that with careful patient selection and skilled surgical execution, the utilization of ICG fluorescence imaging in the laparoscopic resection of retroperitoneal tumors is both safe and effective in children. This approach significantly improves the visualization of critical blood vessels, thus enhancing surgical safety.

Abstract Background With social transformation, rapid economic development and deepening awareness of psychological health in China, people’s demand for psychological health services is becoming increasingly urgent. A key challenge for Chinese medical organizations is to train enough qualified psychological care nurses. A greater understanding of psychological care competences (PCC) can help in clinical nurse selection, training, and assessment. Objective To develop a PCC framework for Chinese nurses and obtain a consensus on the framework among experts. Methods A descriptive mixed methods study was designed consisting of a literature review and semi-structured interviews followed by three Delphi rounds. The experts (n = 16) involved were nurses, nursing managers and educators from nine Chinese provinces with a specific interest in psychological care. Descriptive statistics assisted in data analysis. Results Using the Iceberg Model as a theoretical foundation, five main dimensions and associated subdomains were integrated from 39 chosen articles. The semi-structured interviews with 24 nursing managers and nurses confirmed all of the themes from the literature review while generating new themes, both of which were incorporated into the initial PCC framework. After three Delphi rounds, the experts reached consensus on the PCC framework, including five domains (knowledge, skills, professional ethics, personal traits, internal motivations) and 22 subdomains with connotations. The response rate (RR) values for the three rounds of consultation were 80.00%, 87.50% and 92.86%, the composite reliability (Cr) values were 0.89–0.90, and the Kendall coordination coefficients were 0.155-0.200 (P

Purposes Event extraction is a prerequisite for building high-quality event knowledge graphs. The dependency of event elements exists in the process of clinical event extraction. Existing methods fail to accurately identify event elements and combine them into events, and the amount of available clinical event tagging data is limited. These problems bring great challenges to the event extraction task. Methods In this research, clinical event is extracted and modelled as an entity recognition model, and a Chinese medical event extraction method incorporating multiple features is proposed: BERT-MCRF. In this method, Bidirectional Encoder Representation from Transformers(BERT) is used to construct the embedding and feature extraction parts of the model, multiple word sliding window features in the Conditional Random Fields(CRF) layer are added, then BERT-MCRF is used as a base experiment for semi-supervised experiments, and a high confidence pseudo-labeled data is proposed. The selection algorithm is used as a condition to filter the data, and 300 data of higher quality are obtained and merged with the original data. Finally, 1 700 corpus are constructed and the model is retrained. Findings The overall F1 value of the BERT-MCRF model on the three attribute entities reaches 80.21%, which is 15.11% better than that of the classical Bi-directional Long Short Term Memory-Conditional Random Fields (BiLSTM-CRF) model; with the model retrained by the semi-supervised idea, the final F1 value reaches 81.56%, which is 1.35% higher than the original BERT-MCRF.

Abstract High‐coverage mass spectrometry analysis of single‐cell metabolomics remains challenging due to the extremely low abundance and wide polarity of metabolites and ultra‐small volume in single cells. Herein, a novel concentric hybrid ionization source, nanoelectrospray ionization‐atmospheric pressure chemical ionization (nanoESI‐APCI), is ingeniously designed to detect polar and nonpolar metabolites simultaneously in single cells. The source is constructed by inserting a pulled glass capillary coaxially into a glass tube that acts as a dielectric barrier layer. Benefitting from the integrated advantages of nanoESI and APCI, its limit of detection is improved by one order of magnitude to 10 pg mL−1. After the operational parameter optimization, 254 metabolites detected in nanoESI‐APCI are tentatively identified from a single cell, and 82 more than those in nanoESI. The developed nanoESI‐APCI is successively applied to study the metabolic heterogeneity of human hepatocellular carcinoma tissue microenvironment united with laser capture microdissection (LCM), the discrimination of cancer cell types and subtypes, the metabolic perturbations to glucose starvation in MCF7 cells and the metabolic regulation of cancer stem cells. These results demonstrated that the nanoESI‐APCI not only opens a new avenue for high‐coverage and high‐sensitivity metabolomics analysis of single cell, but also facilitates spatially resolved metabolomics study coupled with LCM.

(E)-β-Farnesene (EBF) serves as the primary component of the alarm pheromone used by most aphid pest species. Pyrethrum (Tanacetum cinerariifolium) exhibits tissue-specific regulation of EBF accumulation and release, effectively mimicking the aphid alarm signal, deterring aphid attacks while attracting aphid predators. However, cultivated chrysanthemum (Chrysanthemum morifolium), a popular and economically significant flower, is highly vulnerable to aphid infestations. In this study, we investigated the high expression of the pyrethrum EBF synthase (TcEbFS) gene promoter in the flower head and stem, particularly in the parenchyma cells. Subsequently, we introduced the TcEbFS gene, under the control of its native promoter, into cultivated chrysanthemum. This genetic modification led to increased EBF accumulation in the flower stem and young flower bud, which are the most susceptible tissues to aphid attacks. Analysis revealed that aphids feeding on transgenic chrysanthemum exhibited prolonged probing times and extended salivation durations during the phloem phase, indicating that EBF in the cortex cells hindered their host-location behavior. Interestingly, the heightened emission of EBF was only observed in transgenic chrysanthemum flowers after mechanical damage. Furthermore, we explored the potential of this transgenic chrysanthemum for aphid resistance by comparing the spatial distribution and storage of terpene volatiles in different organs and tissues of pyrethrum and chrysanthemum. This study provides valuable insights into future trials aiming for a more accurate replication of alarm pheromone release in plants. It highlights the complexities of utilizing EBF for aphid resistance in cultivated chrysanthemum and calls for further investigations to enhance our understanding of this defense mechanism.

Abstract Single‐stranded DNA oligonucleotides wrapping on the surface of single‐walled carbon nanotubes (SWCNTs), described as DNA corona, are often used as a dispersing agent for SWCNTs. The uneven distribution of DNA corona along SWCNTs is related to the photoelectric properties and the surface activity of SWCNTs. An ionic strength‐mediated “DNA corona defects” (DCDs) strategy is proposed to acquire an exposed surface of SWCNTs (accessible surface) as large as possible while maintaining good dispersibility via modulating the conformation of DNA corona. By adjusting the solution ionic strength, the DNA corona phase transitioned from an even‐distributed and loose conformation to a locally compact conformation. The resulting enlarged exposed surface of SWCNTs is called DCDs, which provide active sites for molecular adsorption. This strategy is applied for the arrangement of SWCNTs on DNA origami. SWCNTs with ≈11 nm DCD, providing enough space for the adsorption of “capture ssDNA” (≈7 nm width required for 24‐nt) extended from DNA origami structures are fabricated. The DCD strategy has potential applications in SWCNT‐based optoelectronic devices.

The lymphoma incidence rate is on the rise, with invasive forms particularly prone to relapse following conventional treatment, posing a significant threat to human life and wellbeing. Numerous studies have shown that traditional Chinese botanical drug medicine offers promising therapeutic benefits for various malignancies, with previous experimental findings indicating that Celastrus orbiculatus extract effectively combats digestive tract tumors. However, its impact on lymphoma remains unexplored. This study aims to investigate the impact and underlying mechanisms of COE on the proliferation and apoptosis of Burkitt lymphoma cells. We diluted COE in RPMI-1640 medium to create various working concentrations and introduced it to human Burkitt lymphoma Raji and Ramos cells. To evaluate cell viability, we used the CCK-8 assay, and we observed morphological changes using HE staining. We also conducted Annexin V-PI and JC-1 staining experiments to assess apoptosis. By combining the cell cycle experiment with the EDU assay, we gained insights into the effects of COE on DNA replication in lymphoma cells. Using Western blotting, we detected alterations in apoptosis-related proteins. In vivo experiments revealed that following COE intervention, tumor volume decreased, survival time was prolonged, spleen size reduced, and the expression of tumor apoptosis-related proteins changed. Our findings indicate that COE effectively inhibits lymphoma cell proliferation and promotes apoptosis by regulating these apoptosis-related proteins.

Background: Transition shock is prevalent among nursing interns. Future time perspective helps nursing interns learn and work more effectively and improve their problem-solving skills. Professional self-concept and professional identity play an important central and driving role in nursing interns' career choices and career development. However, the mechanism by which future time perspective, professional self-concept and professional identity are linked to transition shock among nursing interns remains unknown. Objectives: We assess the degree of transition shock experienced by nursing interns and investigate the connections among transition shock, future-focused viewpoint, professional identity, and professional self-concept. Design: A descriptive, cross-sectional design was conducted. Setting: Eight hospitals in Hunan Province, China were included in the study. Participants: Nursing interns at the studied hospital participated in the study. Methods: A total of 1090 nursing interns [929 female, 161 male] were recruited from eight hospitals. Data on transition shock, future time perspective, professional self-concept and professional identity among nursing interns were collected using questionnaires from 30 May to June 15, 2022. Results: On a 4-point rating scale, the participants' felt transition shock had a mean overall score of 2.39 (SD = 0.52). The dimension with the highest score was overwhelming workload (mean = 2.74, SD = 0.58), while the dimension with the lowest score was incongruity between work and personal life (mean = 2.16, SD = 0.70).Professional identity was statistically significantly correlated with transition shock (r = −0.198, p

Abstract Objective Xinyang Tablet (XYT) has emerged as a potential intervention to counter sepsis-induced myocardial dysfunction (SMID) by influencing macrophage autophagy and M2 polarization. This study aimed to unravel the underlying mechanism of XYT in sepsis-induced myocardial dysfunction (SIMD). Methods A microarray analysis was employed to explore sepsis-related changes, and bioinformatics analysis was used to predict lncRNAs binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). This studio utilized SIMD mouse models induced by lipopolysaccharide (LPS) injection, followed by treatments involving varied doses of XYT, digoxin (positive control), or si-LncSICRNT1. After seven days, evaluations encompassing mouse hair/mental state/diet/weight were measured, and cardiac function via echocardiography were conducted. Myocardial tissue changes were observed using hematoxylin–eosin staining. Additionally, bone marrow-derived macrophages (BMDMs) subjected to LPS for M1 polarization were treated with oe-LncSICRNT1, si-TRAF6 and their negative control, XYT, or autophagy inhibitor 3-Methyladenine (3-MA) (positive control). RT-qPCR and Western blot analyses were employed to assess LncSICRNT1, TRAF6, Beclin-1, LC3II/LC3I, and p62 levels. Immunohistochemistry and flow cytometry were used for M1/M2 polarization markers, while enzyme-linked immunosorbent assay (ELISA) gauged inflammatory factor levels. Interaction between TRAF6 and LncSICRNT1 was probed using RNA pull-down and RNA immunoprecipitation (RIP) assays. Results Chip analysis obtained 1463 differentially expressed lncRNAs, including LINC01550 (LncSICRNT1). Further prediction indicated that LncSICRNT1 was highly likely to directly bind to TRAF6. XYT treatment in LPS-induced SIMD mice led to notable enhancements in sleep/hair/diet/activity, increased weight/left ventricular end-diastolic diameter (LVEDd)/LV ejection fraction (LVEF)/LV fraction shortening (LVFS). These improvements were associated with elevated LncSICRNT1 expression and decreased TRAF6 protein levels, culminating in reduced myocardial inflammatory responses and improved cardiac function. Notably, XYT was found to suppress macrophage M1 polarization, while enhancing M2 polarization, ultimately benefitting cardiac function via LncSICRNT1 modulation. Furthermore, the study revealed LncSICRNT1 modulated Beclin-1 ubiquitination and restrained macrophage autophagy by targeting TRAF6 expression. Conclusion The study highlights XYT’s potential to ameliorate LPS-induced SIMD by elevating LncSICRNT1 expression, influencing TRAF6 expression, and regulating Beclin-1 ubiquitination. These actions collectively inhibit macrophage autophagy and foster M1/M2 polarization, contributing to cardiac function improvement.

Abstract Cancer stem-like cells (CSCs) contribute to cancer metastasis, drug resistance and tumor relapse, yet how amino acid metabolism promotes CSC maintenance remains exclusive. Here, we identify that proline synthetase PYCR1 is critical for breast cancer stemness and tumor growth. Mechanistically, PYCR1-synthesized proline activates cGMP-PKG signaling to enhance cancer stem-like traits. Importantly, cGMP-PKG signaling mediates psychological stress-induced cancer stem-like phenotypes and tumorigenesis. Ablation of PYCR1 markedly reverses psychological stress-induced proline synthesis, cGMP-PKG signaling activation and cancer progression. Clinically, PYCR1 and cGMP-PKG signaling components are highly expressed in breast tumor specimens, conferring poor survival in breast cancer patients. Targeting proline metabolism or cGMP-PKG signaling pathway provides a potential therapeutic strategy for breast patients undergoing psychological stress. Collectively, our findings unveil that PYCR1-enhanced proline synthesis displays a critical role in maintaining breast cancer stemness.

Abstract. Background:. Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca2+ homeostasis. The present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation (small ubiquitin-like modifier) process after ischemia/reperfusion injury (I/RI) in vitro and in vivo. Methods:. Calcium transient and systolic/diastolic function of cardiomyocytes isolated from Serca2a knockout (KO) and wild-type mice with I/RI were compared. SUMO-relevant protein expression and localization were detected by quantitative real-time PCR (RT-qPCR), Western blotting, and immunofluorescence in vitro and in vivo. Serca2a-SUMOylation, infarct size, and cardiac function of Senp1 or Senp2 overexpressed/suppressed adenovirus infected cardiomyocytes, were detected by immunoprecipitation, triphenyltetrazolium chloride (TTC)-Evans blue staining, and echocardiography respectively. Results:. The results showed that the changes of Fura-2 fluorescence intensity and contraction amplitude of cardiomyocytes decreased in the I/RI groups and were further reduced in the Serca2a KO + I/RI groups. Senp1 and Senp2 messenger ribose nucleic acid (mRNA) and protein expression levels in vivo and in cardiomyocytes were highest at 6 h and declined at 12 h after I/RI. However, the highest levels in HL-1 cells were recorded at 12 h. Senp2 expression increased in the cytoplasm, unlike that of Senp1. Inhibition of Senp2 protein reversed the I/RI-induced Serca2a-SUMOylation decline, reduced the infarction area, and improved cardiac function, while inhibition of Senp1 protein could not restore the above indicators. Conclusion:. I/RI activated Senp1 and Senp2 protein expression, which promoted Serca2a-deSUMOylation, while inhibition of Senp2 expression reversed Serca2a-SUMOylation and improved cardiac function.

Abstract Background Polypyrimidine tract binding protein 1 (PTBP1) has been found to play an important role in the occurrence and development of various tumors. At present, the role of PTBP1 in gastric cancer (GC) is still unknown and worthy of further investigation. Methods We used bioinformatics to analyze the expression of PTBP1 in patients with GC. Cell proliferation related experiments were used to detect cell proliferation after PTBP1 knockdown. Skeleton staining, scanning electron microscopy and transmission electron microscopy were used to observe the changes of actin skeleton. Proliferation and actin skeleton remodeling signaling pathways were detected by Western Blots. The relationship between PTBP1 and proliferation of gastric cancer cells was further detected by subcutaneous tumor transplantation. Finally, tissue microarray data from clinical samples were used to further explore the expression of PTBP1 in patients with gastric cancer and its correlation with prognosis. Results Through bioinformatics studies, we found that PTBP1 was highly expressed in GC patients and correlated with poor prognosis. Cell proliferation and cycle analysis showed that PTBP1 down-regulation could significantly inhibit cell proliferation. The results of cell proliferation detection related experiments showed that PTBP1 down-regulation could inhibit the division and proliferation of GC cells. Furthermore, changes in the morphology of the actin skeleton of cells showed that PTBP1 down-regulation inhibited actin skeletal remodeling in GC cells. Western Blots showed that PTBP1 could regulate proliferation and actin skeleton remodeling signaling pathways. In addition, we constructed PTBP1 Cas9-KO mouse model and performed xenograft assays to further confirm that down-regulation of PTBP1 could inhibit the proliferation of GC cells. Finally, tissue microarray was used to further verify the close correlation between PTBP1 and poor prognosis in patients with GC. Conclusions Our study demonstrates for the first time that PTBP1 may affect the proliferation of GC cells by regulating actin skeleton remodeling. In addition, PTBP1 is closely related to actin skeleton remodeling and proliferation signaling pathways. We suppose that PTBP1 might be a potential target for the treatment of GC. Graphical abstract

Abstract Objective Despite strong evidence on the safety and tolerability of the COVID‐19 vaccine, data on vaccination in children with epilepsy, particular younger children with specific epilepsy syndromes, are limited. The protective effects of vaccination against seizure increase upon COVID‐19 infection also remain to be elucidated. Methods Questionnaire surveys were distributed online via an established WeChat group for patient management as well as in our outpatient clinic. The data collected included demographics and clinical information related to COVID‐19 vaccination and infection. Detailed information related to epilepsy diagnosis and treatment was also collected from our patient database. Logistic regression analysis was performed to determine the factors associated with non‐vaccination. The characteristics of seizures following COVID‐19 infection were described. Results In total, 354 suitable questionnaires were included in the study. The median age at survey was 6 years (interquartile range 4, 9). The most common epilepsy syndrome was self‐limited epilepsy (n = 153, 43.2%), followed by developmental and/or epileptic encephalopathy (D/EE, n = 81, 22.9%) and genetic generalized epilepsy (n = 59, 16.7%). The vaccine uptake rate was 43.8% (n = 155), and all related side‐effects (n = 11, 7.1%) remitted spontaneously. Younger age (odds ratio [OR] = 0.877, P = 0.001), D/EE (OR = 5.096, P = 0.008), and less than six months seizure‐freedom before vaccination (OR = 3.026, P = 0.005) were associated with unwillingness to be vaccinated. There were no significant differences in the rate of COVID‐19 infection (33.7% vs 32.7%, P = 0.879) and resultant increased seizure activity following infection between the vaccinated and unvaccinated groups after propensity score matching (9.1% vs 15.6%, P = 0.428).Three unvaccinated cases of Dravet syndrome developed status epilepticus following COVID‐19 infection. Significance Vaccination against COVID‐19 is safe and well tolerated in children, even in younger patients with D/EE. Although the risk of worsening seizures following COVID‐19 infection may not be reduced by immunization, education focused on increased vaccination in pediatric epilepsy is still warranted.

Background and objective The treatment and diagnosis of non-small cell lung cancer (NSCLC) is still a difficult problem in the medical community, and exploring the molecular mechanism of the occurrence and development of NSCLC is a hot topic of the current research. Long non-coding RNA (lncRNA) NORAD is highly expressed in a variety of cancer cells. It may be a molecular target that promotes NSCLC. The aim of this study was to investigate the impacts of lncRNA NORAD on the proliferation, apoptosis, and chemosensitivity of NSCLC by regulating zinc finger protein 217 (ZNF217) through miR-199a-3p. Methods Real-time quantitative polymerase chain reaction (qRT-PCR) method was applied to detect the expressions of NORAD, miR-199a-3p and ZNF217 genes in normal lung epithelial cells BEAS-2B, lung cancer H460 cells, and Cisplatin (DDP) resistant cell lines H460/DDP. H460/DDP cells were devided into control group, si-NC group, si-NORAD group, miR-NC group, miR-199a-3p mimic group, si-NORAD+inhibitor NC group and si-NORAD+miR-199a-3p inhibitor group. Cell proliferation, apoptosis, the expression of NORAD, miR-199a-3p and ZNF217 genes of cells in each group were detected and the expression levels of Ki-67, caspase-9 and ZNF217 proteins in different cells were also observed. The relationship between miR-199a-3p, NORAD and ZNF217 was vefified. Results Compared with BEAS-2B cells, the expressions of NORAD, ZNF217 mRNA were significantly increased in H460 and H460/DDP cells (P

ObjectiveTo compare the effects of different selective sodium-glucose cotransporter-2 inhibitors (SGLT2i) on hemoglobin and hematocrit in patients with type 2 diabetes mellitus (T2DM) with a network meta-analysis (NMA).MethodsRandomized controlled trials (RCTs) on SGLT2i for patients with T2DM were searched in PubMed, Embase, Cochrane Library, and Web of Science from inception of these databases to July 1, 2023. The risk of bias (RoB) tool was used to evaluate the quality of the included studies, and R software was adopted for data analysis.ResultsTwenty-two articles were included, involving a total of 14,001 T2DM patients. SGLT2i included empagliflozin, dapagliflozin, and canagliflozin. The NMA results showed that compared with placebo, canagliflozin 100mg, canagliflozin 300mg, dapagliflozin 10mg, dapagliflozin 2mg, dapagliflozin 50mg, dapagliflozin 5mg, empagliflozin 25mg, and dapagliflozin 20mg increased hematocrit in patients with T2DM, while canagliflozin 100mg, canagliflozin 200mg, canagliflozin 300mg increased hemoglobin in patients with T2DM. In addition, the NMA results indicated that canagliflozin 100mg had the best effect on the improvement of hematocrit, and canagliflozin 200mg had the best effect on the improvement of hemoglobin.ConclusionBased on the existing studies, we concluded that SGLT2i could increase hematocrit and hemoglobin levels in patients with T2DM, and canagliflozin 100mg had the best effect on the improvement of hematocrit, while canagliflozin 200mg had the best effect on the improvement of hemoglobin.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#loginpage, identifier PROSPERO (CRD42023477103).

Hirudo nipponia is an important medicinal animal in China. Its salivary gland secretions contain a variety of protein bioactive substances. Investigations of its salivary glands are of great significance in the study of the medicinal value and mechanism of leech secretions. Illumina RNA-Seq technology was used to perform transcriptome sequencing of salivary gland tissue of H. nipponia under starvation (D30) and fed (D0) states. A total of 2,650 differentially expressed genes (DEGs) were screened. Using the label-free protein quantification technique and bioinformatics analysis, the expression of differentially expressed proteins (DEPs) in the salivary gland tissue of H. nipponia was compared. A total of 2,021 proteins were identified, among which 181 proteins were differentially expressed between the starvation and fed states, with 72 significantly upregulated and 109 significantly downregulated. The salivary glands of H. nipponia synthesized protein-based active substances after 30 days of starvation and adapted to the starvation environment by weakening respiratory activity and reducing metabolic activity to reduce energy expenditure. Energy was produced by glycolysis and the tricarboxylic acid cycle for the synthesis of substances such as antibiotics. This study combined transcriptome and proteome sequencing data to provide a data reference for an in-depth study of the regulatory mechanism of salivary gland secretions of H. nipponia under starvation stress by analyzing DEGs and DEPs.

Key Clinical Message Immunotherapy may be ineffective in the advanced stages of anti‐IgLON5 disease with psychiatric symptoms. The psychiatric symptoms in advanced stages of anti‐IgLON5 disease may be associated with neurodegeneration.

Although the global pandemic of SARS-CoV-2 has passed, there are still regional outbreaks that continue to jeopardize human health. Hence, there is still a great deal of interest in developing an efficient vaccine that can quickly and effectively prevent reemerging outbreaks of SARS-CoV-2. Delta variant was once a dominant strain in the world in 2021, and we first constructed a recombinant RBDdelta-Fc fusion vaccine by coupling the RBD of Delta variant with the human Fc fragment. This Fc fusion strategy increases the immunogenicity of the recombinant RBD vaccine, with a long-lasting high level of IgG antibodies and neutralizing antibodies induced by RBDdelta-Fc vaccine. This RBDdelta-Fc vaccine, as well as the RBD-Fc vaccine prepared in our previously study, could trigger a durable immune effect by the heterologous boosting immunity, and the RBD-Fc induced a quicker humoral immune response than the homologous immunization with inactivated vaccines. In conclusion, the Fc fusion strategy has a significant role in enhancing the immunogenicity of recombinant protein vaccines, thus promising the development of a safe and efficient vaccine for the heterologous boosting against SARS-CoV-2.

Objective: Pre-treatment enhanced CT image data were used to train and build models to predict the efficacy of non-small cell lung cancer after conventional radiotherapy and chemotherapy using two classification algorithms, Logistic Regression (LR) and Gaussian Naive Baye (GNB). Methods: In this study, we used pre-treatment enhanced CT image data for region of interest (ROI) sketching and feature extraction. We utilized the least absolute shrinkage and selection operator (LASSO) mutual confidence method for feature screening. We pre-screened logistic regression (LR) and Gaussian naive Bayes (GNB) classification algorithms and trained and modeled the screened features. We plotted 5-fold and 10-fold cross-validated receiver operating characteristic (ROC) curves to calculate the area under the curve (AUC). We performed DeLong's test for validation and plotted calibration curves and decision curves to assess model performance. Results: A total of 102 patients were included in this study, and after a comparative analysis of the two models, LR had only slightly lower specificity than GNB, and higher sensitivity, accuracy, AUC value, precision, and F1 value than GNB (training set accuracy: 0.787, AUC value: 0.851; test set accuracy: 0.772, AUC value: 0.849), and the LR model has better performance in both the decision curve and the calibration curve. Conclusion: CT can be used for efficacy prediction after radiotherapy and chemotherapy in NSCLC patients. LR is more suitable for predicting whether NSCLC prognosis is in remission without considering the computing speed.

Abstract Neonatal bacterial meningitis is serious and accounts for high morbidity and mortality in developing countries, but the duration of antimicrobial treatment is not well established. Cerebrospinal fluid (CSF) levels are important factors for diagnosing and monitoring the occurrence and development of bacterial meningitis. In this study, we aimed to compare the clinical characteristics and outcomes of neonatal bacterial meningitis with normal CSF and abnormal CSF at discharge. We enrolled neonates with bacterial meningitis who were admitted to the neonatology department of the Children's Hospital of Chongqing Medical University between August 1, 2019 and January 1, 2021. The children's clinical data, laboratory data, and outcomes were recorded and analyzed. Fifty‐five neonates met the inclusion criteria in our study. Other than CSF protein levels, there was no significant difference in clinical symptoms, blood levels (white blood cell [WBC] count, neutrophils, platelets, C‐reactive protein, and procalcitonin), CSF WBC counts at admission and discharge, duration of antibiotics, or hospital stays between the two groups (p > 0.05). For the sequelae of bacterial meningitis, short‐ and long‐term complications also showed no statistically significant differences between the two groups. The duration of antimicrobial therapy in neonatal bacterial meningitis may depend on the clinical condition of the patient rather than the CSF levels. This study may improve the reasonable utilization of antibiotics in neonatal bacterial meningitis.

BackgroundWith the rapid development of artificial intelligence (AI) and the widespread use of ChatGPT, nursing students’ artificial intelligence quotient (AIQ), employability, cognition, and demand for ChatGPT are worthy of attention. ObjectiveWe aimed to investigate Chinese nursing students’ AIQ and employability status as well as their cognition and demand for the latest AI tool—ChatGPT. This study was conducted to guide future initiatives in nursing intelligence education and to improve the employability of nursing students. MethodsWe used a cross-sectional survey to understand nursing college students’ AIQ, employability, cognition, and demand for ChatGPT. Using correlation analysis and multiple hierarchical regression analysis, we explored the relevant factors in the employability of nursing college students. ResultsIn this study, out of 1788 students, 1453 (81.30%) had not used ChatGPT, and 1170 (65.40%) had never heard of ChatGPT before this survey. College students’ employability scores were positively correlated with AIQ, self-regulation ability, and their home location and negatively correlated with school level. Additionally, men scored higher on college students’ employability compared to women. Furthermore, 76.5% of the variance was explained by the multiple hierarchical regression model for predicting college students’ employability scores. ConclusionsChinese nursing students have limited familiarity and experience with ChatGPT, while their AIQ remains intermediate. Thus, educators should pay more attention to cultivating nursing students’ AIQ and self-regulation ability to enhance their employability. Employability, especially for female students, those from rural backgrounds, and students in key colleges, deserves more attention in future educational efforts.

Abstract Background Plant-derived exosomes-like nanovesicles (PDENs) have been found to be advantageous in disease treatment and drug delivery, but research on their biogenesis, compositional analysis, and key marker proteins is still in its infancy, which limits the standardized production of PDENs. Efficient preparation of PDENs continues to be a major challenge. Results Novel PDENs-based chemotherapeutic immune modulators, Catharanthus roseus (L.) Don leaves-derived exosome-like nanovesicles (CLDENs) were isolated from apoplastic fluid. CLDENs were membrane structured vesicles with a particle size of 75.51 ± 10.19 nm and a surface charge of −21.8 mV. CLDENs exhibited excellent stability, tolerating multiple enzymatic digestions, resisting extreme pH environments, and remaining stable in the gastrointestinal simulating fluid. Biodistribution experiments showed that CLDENs could be internalized by immune cells, and targeted at immune organs after intraperitoneal injection. The lipidomic analysis revealed CLDENs’ special lipid composition, which contained 36.5% ether-phospholipids. Differential proteomics supported the origin of CLDENs in multivesicular bodies, and six marker proteins of CLDENs were identified for the first time. 60 ~ 240 μg/ml of CLDENs promoted the polarization and phagocytosis of macrophages as well as lymphocyte proliferation in vitro. Administration of 20 mg/kg and 60 mg/kg of CLDENs alleviated white blood cell reduction and bone marrow cell cycle arrest in immunosuppressive mice induced by cyclophosphamide. CLDENs strongly stimulated the secretion of TNF-α, activated NF-κB signal pathway and increased the expression of the hematopoietic function-related transcription factor PU.1 both in vitro and in vivo. To ensure a steady supply of CLDENs, plant cell culture systems of C. roseus were established to provide CLDENs-like nanovesicles which had similar physical properties and biological activities. Gram-level nanovesicles were successfully obtained from the culture medium, and the yield was three times as high as the original. Conclusions Our research supports the use of CLDENs as a nano-biomaterial with excellent stability and biocompatibility, and for post-chemotherapy immune adjuvant therapy applications. Graphical Abstract

Pacific white shrimp (Penaeus vannamei) is one of the main shrimp species cultivated around the world. Despite its high yields and easy handling, water pollution from intensive shrimp cultivation remains a serious problem in China. In this study, a compound aquaculture model of P. vannamei and water spinach (Ipomoea aquatica) was used to investigate the effect of a water spinach floating raft on water quality, antioxidants, non-specific immune response, growth performance, and microbial diversity. The experimental design of this study consisted of two groups with three replicates for each, i.e., control group: aquatic monoculture (AM) system with only P. vannamei; treatment group: P. vannamei-I. aquatica raft aquaponics (AP) system with a 50% cover ratio with a water spinach floating raft. The experiment lasted for seven weeks. The results show that the concentrations of total phosphorus (TP), total nitrogen (TN), nitrate nitrogen (NO3−-N), ammonia nitrogen (NH4+-N), nitrite nitrogen (NO2−-N), and active phosphorus (AP) in the AM group were higher than those in the AP group at different sampling times. The water quality index of the AP group was better than that of the AM group, indicating that water spinach can remove the nutrients from aquaculture water bodies. The average daily gain and survival rate of shrimp in the AP group were higher than those in the AM group. The total antioxidant capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and acid phosphatase (ACP) in the AP group were better than those in the AM group. The Shannon–Wiener and Simpson indices of the gut, water, and sediment of the AP system were significantly higher than those in the AM system, which implied a higher abundance of microorganisms in the AP system. These results demonstrate that the application of a water spinach floating raft in aquaponics can not only improve the water quality, but also improve the growth performance, antioxidant system, and non-specific immune responses of Pacific white shrimp, while increasing the abundance of microorganisms in the aquaculture system and improving the ecological benefits in terms of the expenditure.

Abstract In this manuscript, a simple method combining atomic layer deposition and magnetron sputtering is developed to fabricate high‐performance Pd/SnO2 film patterns applied for micro‐electro‐mechanical systems (MEMS) H2 sensing chips. SnO2 film is first accurately deposited in the central areas of MEMS micro hotplate arrays by a mask‐assistant method, leading the patterns with wafer‐level high consistency in thickness. The grain size and density of Pd nanoparticles modified on the surface of the SnO2 film are further regulated to obtain an optimized sensing performance. The resulting MEMS H2 sensing chips show a wide detection range from 0.5 to 500 ppm, high resolution, and good repeatability. Based on the experiments and density functional theory calculations, a sensing enhancement mechanism is also proposed: a certain amount of Pd nanoparticles modified on the SnO2 surface could bring stronger H2 adsorption followed by dissociation, diffusion, and reaction with surface adsorbed oxygen species. Obviously, the method provided here is quite simple and effective for the manufacturing of MEMS H2 sensing chips with high consistency and optimized performance, which may also find broad applications in other MEMS chip technologies.

Facial amphiphilicity is an extraordinary chemical structure feature of a variety of antimicrobial peptides and polymers. Vast efforts have been dedicated to small molecular, macromolecular and dendrimer-like systems to mimic this highly preferred structure or conformation, including local facial amphiphilicity and global amphiphilicity. This work conceptualizes Facial Amphiphilicity Index (FAI) as a numerical value to quantitatively characterize the measure of chemical compositions and structural features in dictating antimicrobial efficacy. FAI is a ratio of numbers of charges to rings, representing both compositions of hydrophilicity and hydrophobicity. Cationic derivatives of multicyclic compounds were evaluated as model systems for testing antimicrobial selectivity against Gram-negative and Gram-positive bacteria. Both monocyclic and bicyclic compounds are non-antimicrobial regardless of FAIs. Antimicrobial efficacy was observed with systems having larger cross-sectional areas including tricyclic abietic acid and tetracyclic bile acid. While low and high FAIs respectively lead to higher and lower antimicrobial efficacy, in consideration of cytotoxicity, the sweet spot is typically suited with intermediate FAIs for each specific system. This can be well explained by the synergistic hydrophobic-hydrophobic and electrostatic interactions with bacterial cell membranes and the difference between bacterial and mammalian cell membranes. The adoption of FAI would pave a new avenue toward the design of next-generation antimicrobial macromolecules and peptides.

Glioblastoma is the most common malignant tumor in the adult primary central nervous system. It has a strong proliferative ability, high recurrence rate, and high malignant degree. Despite standard radiotherapy combined with temozolomide chemotherapy, the prognosis was poor, with a 5-year survival of

Accurate detection of antigen p24 for HIV−1 early diagnosis remains challenging. Here the authors present a click chemistry amplified nanopore (CAN) assay that allows p24 quantification at ultralow concentration range in clinical samples.

Green development is an important direction of international economic and social development, and the green management practice of enterprises is the decisive factor to realize green development. This paper collected the data of green management and carbon performance of China paper enterprises through a questionnaire, from the perspective of measuring green management from management consciousness and management ability, applied the fixed-effect model to test the impact of management awareness and management ability on the carbon performance of paper enterprises, and explored mediation effect of management behavior of paper enterprises between management consciousness, management ability and carbon performance. The research results show that green management awareness and management ability positively affect carbon performance of paper enterprises; management behavior has a mediation effect between management awareness and management ability and corporate carbon performance; heterogeneity analysis shows that the positive impact of green management awareness and management ability on carbon performance varies due to establishment time, size, nature and regional differences.

The mortality rate of patients with coronary artery disease (CAD) increases year by year, and the age of onset is decreasing, primarily because of the lack of an efficient and convenient diagnostic method for CAD. In the present study, we aimed to detect CAD‐correlated biomarkers and the regulatory pathways involved through weighted co‐expression network analysis. The microarray data originated from 93 CAD patients and 48 controls within the Gene Expression Omnibus (GEO) database. The gene network was implemented by weighted gene co‐expression network analysis, and the genes were observed to fall into a range of modules. We took the intersection of genes in the modules most correlated with CAD with the differentially expressed genes of CAD, which were identified by applying the limma package. Lasso regression and support vector machine recursive feature elimination algorithms were used to determine CAD candidate signature genes. The biomarkers for diagnosing CAD were detected by validating candidate signature gene diagnostic capabilities (receiver operating characteristic curves) based on data sets from GEO. Three modules were selected, and 26 vital genes were identified. Eight of these genes were reported as the optimal candidate features in terms of CAD diagnosis. Through receiver operating characteristic curve analysis, we identified three genes (ERCC5, HES6 and RORA; area under the curve > 0.8) capable of distinguishing CAD from the control, and observed that these genes are correlated with the immune response. In summary, ERCC5, HES6 and RORA may have potential for diagnosis of CAD.

Abstract Objective The phenotype of the chromosomal aberration 47, XXY exhibits considerable heterogenicity. In addition, epilepsy is extremely uncommon in individuals with this chromosomal disorder. As a result, the clinical characteristics of epilepsy in these patients remain poorly understood. Methods Clinical data and the evolution of epilepsy in a boy diagnosed with chromosomal aberration 47, XXY were collected and analyzed. Furthermore, a systematic literature review was conducted to examine the relationship between chromosomal aberration 47, XXY and epilepsy in children. Results We identified a novel phenotype associated with the chromosomal anomaly 47, XXY in a 2‐year‐2‐month‐old boy who presented with self‐limited epilepsy with autonomic seizures at onset, followed by developmental and/or epileptic encephalopathy with spike‐wave activation in sleep (D/EE‐SWAS), which was responsive to corticosteroid treatment. Including the present case, we analyzed 21 cases of children diagnosed with epilepsy due to the presence of the 47, XXY chromosomal anomaly. The most common types of epilepsy were focal combined generalized epilepsy (n = 9), epileptic spasms (n = 6), and generalized epilepsy (n = 4). There were six cases of infantile epileptic spasm syndrome (IESS) (n = 5) and developmental and epileptic encephalopathy (n = 1), one case of Lennox–Gastaut syndrome, and one case of D/EE‐SWAS. Apart from corticosteroids in IESS, 15 antiseizure medications (ASMs) were prescribed to eight children in this cohort, with valproate (n = 5) being the most frequently used. Conclusions The epilepsy types and syndromes associated with the chromosomal anomaly 47, XXY demonstrated considerable heterogeneity. Among the observed phenotypes, IESS and focal epilepsy, which displayed partial responsiveness to multiple ASMs, were the most prevalent.

BackgroundDiabetic kidney disease (DKD) is a common complication of diabetes that is clinically characterized by progressive albuminuria due to glomerular destruction. The etiology of DKD is multifactorial, and numerous studies have demonstrated that cellular senescence plays a significant role in its pathogenesis, but the specific mechanism requires further investigation.MethodsThis study utilized 5 datasets comprising 144 renal samples from the Gene Expression Omnibus (GEO) database. We obtained cellular senescence-related pathways from the Molecular Signatures Database and evaluated the activity of senescence pathways in DKD patients using the Gene Set Enrichment Analysis (GSEA) algorithm. Furthermore, we identified module genes related to cellular senescence pathways through Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm and used machine learning algorithms to screen for hub genes related to senescence. Subsequently, we constructed a cellular senescence-related signature (SRS) risk score based on hub genes using the Least Absolute Shrinkage and Selection Operator (LASSO), and verified mRNA levels of hub genes by RT-PCR in vivo. Finally, we validated the relationship between the SRS risk score and kidney function, as well as their association with mitochondrial function and immune infiltration.ResultsThe activity of cellular senescence-related pathways was found to be elevated among DKD patients. Based on 5 hub genes (LIMA1, ZFP36, FOS, IGFBP6, CKB), a cellular senescence-related signature (SRS) was constructed and validated as a risk factor for renal function decline in DKD patients. Notably, patients with high SRS risk scores exhibited extensive inhibition of mitochondrial pathways and upregulation of immune cell infiltration.ConclusionCollectively, our findings demonstrated that cellular senescence is involved in the process of DKD, providing a novel strategy for treating DKD.

Abstract Background Building a large-scale medical knowledge graphs needs to automatically extract the relations between entities from electronic medical records (EMRs) . The main challenges are the scarcity of available labeled corpus and the identification of complexity semantic relations in text of Chinese EMRs. A hybrid method based on semi-supervised learning is proposed to extract the medical entity relations from small-scale complex Chinese EMRs. Methods The semantic features of sentences are extracted by a residual network and the long dependent information is captured by bidirectional gated recurrent unit. Then the attention mechanism is used to assign weights for the extracted features respectively, and the output of two attention mechanisms is integrated for relation prediction. We adjusted the training process with manually annotated small-scale relational corpus and bootstrapping semi-supervised learning algorithm, and continuously expanded the datasets during the training process. Results We constructed a small corpus of Chinese EMRs relation extraction based on the EMR datasets released at the China Conference on Knowledge Graph and Semantic Computing. The experimental results show that the best F1-score of the proposed method on the overall relation categories reaches 89.78%, which is 13.07% higher than the baseline CNN.

Objective: To explore the association between the pain-fatigue-sleep disturbance-depression symptom cluster (SC) and cancer-related cognitive impairment (CRCI) in patients having lung cancer and to identify other factors influencing CRCI. Methods: A cross-sectional study was conducted to investigate 378 patients having lung cancer in China from October 2021 to July 2022. The perceived cognitive impairment scale and the general anxiety disorder-7 were used to assess patients’ cognitive impairment and anxiety, respectively. The pain-fatigue-sleep disturbance-depression SC was assessed with the brief fatigue inventory, the brief pain inventory, the Patient Health Questionnaire-9, and the Athens Insomnia Scale. Latent class analysis by Mplus.7.4 was used to identify latent classes of the SC. We adjusted for covariates in the multivariable logistic regression model to examine the relationship between the pain-fatigue-sleep disturbance-depression SC and CRCI. Results: Among patients having lung cancer, two SC classes were identified: high and low symptom burden groups. In the crude model, compared to the low symptom burden group, the high symptom group had greater odds of developing CRCI (odds ratio: 10.065, 95% confidence interval: 4.138–24.478). After adjusting for covariates, in model 1, the high symptom group still had greater odds of developing CRCI (odds ratio: 5.531, 95% confidence interval: 2.133–14.336). Additionally, a diagnosis of over 6 months, anxiety, leisure activity, and a high platelet-to-lymphocyte ratio were found to be influencing factors of CRCI (all P ​

BackgroundMitochondria have long been considered a potential target in cancer therapy because malignant cells are known for their altered energy production. However, there is a lack of comprehensive research on the involvement of mitochondria-associated proteins (MAPs) in neuroblastoma (NB), and their potential as therapeutic targets is yet to be fully explored.MethodsMAP genes were defined based on the protein-coding genes with mitochondrial localization. The mRNA expression patterns and dynamics of MAP genes associated with NB were investigated by integrating publicly available transcriptional profiles at the cellular and tissue levels. Multivariate Cox regression analysis was conducted to reveal the association of MAP genes with the overall survival (OS) and clinical subgroups of NB patients. The single-cell RNA-seq dataset and gene dependency screening datasets were analyzed to reveal the therapeutic potential of targeting MAP genes.ResultsWe compiled a total of 1,712 MAP genes. We found the global and cell type-specific mRNA expression changes of the MAP genes associated with NB status and survival. Our analyses revealed a group of MAP gene signatures independent of MYCN-amplification status associated with NB outcome. We provided computational evidence with selected MAP genes showing good performance in predicting long-term prognosis. By analyzing gene dependency of the MAP genes in NB cell lines and ex vivo human primary T cells, we demonstrated the therapeutic potential of targeting several MAP genes in NB tumors.ConclusionsCollectively, our study provides evidence for the MAP genes as extended candidates in NB tumor stratification and staging, prognostic prediction, and targeted drug development.

PurposeDigital imaging technology and a real-time fluorescent quantitative polymerase chain reaction (RQ-PCR) were used to determine the changes in dental plaque caused by different toothbrushing tools.MethodsA total of 120 subjects were selected and divided into four groups: a manual toothbrush group, a manual toothbrush combined with an oral irrigator group, an electric toothbrush combined with an oral irrigator group, and an electric toothbrush group. We compared the changes in plaque count, plaque area, and colony colonization of the four groups after different cleaning tools had been used for a period of time.ResultsDental plaque count and plaque area decreased in all four groups. The decreases in plaque count and Streptococcus mutans in the electric toothbrush combined with an oral irrigator group were significantly higher than those in other groups.ConclusionElectric toothbrush combined with an oral irrigator shows a good result for plaque removal effect. Digital image analysis combined with biological methods can be used to evaluate dental plaque.

Abstract Background Suicidal ideation in cancer patients is a critical challenge. At present, few studies focus on factors associated with suicidal ideation, and predictive models are still lacking. This study aimed at investigating the risk factors for suicidal ideation among cancer patients, and developed a predictive nomogram to screen high risk cancer patients for early prevention and intervention. Methods A questionnaire survey was conducted among cancer patients between May 2021 and January 2022. The factors associated with suicidal ideation were used to construct a multivariate logistic regression model, which was visualized as a predictive nomogram to evaluate the risk of suicidal ideation. Areas under the curve, calibration plot, decision curve analysis, and internal and external validation were used to validate the discrimination, calibration and clinical usefulness of the model. Results A total of 820 patients with cancer were recruited for this study and 213 (25.98%) developed suicidal ideation. Levels of demoralization, depression and cancer staging, marital status, residence, medical financial burden, and living condition were influence factors for suicidal ideation. Comparing nomogram with Self-rating Idea of Suicide Scale (SIOSS), the nomogram had a satisfactory discrimination ability with an AUC of 0.859 (95% CI: 0.827–0.890) and 0.818 (95% CI: 0.764–0.873) in the training and validation sets, respectively. The calibration plot and decision curve analysis revealed that this nomogram was in good fitness and could be beneficial in clinical applications. Conclusions Suicidal ideation is common in cancer patients. Levels of demoralization, depression and cancer staging were independent predictors of suicidal ideation. The nomogram is an effective and simple tool for predictive suicidal ideation in cancer patients.

Abstract Aberrant RNA splicing produces alternative isoforms of genes to facilitate tumor progression, yet how this process is regulated by oncogenic signal remains largely unknown. Here, we unveil that non-canonical activation of nuclear AURKA promotes an oncogenic RNA splicing of tumor suppressor RBM4 directed by m6A reader YTHDC1 in lung cancer. Nuclear translocation of AURKA is a prerequisite for RNA aberrant splicing, specifically triggering RBM4 splicing from the full isoform (RBM4-FL) to the short isoform (RBM4-S) in a kinase-independent manner. RBM4-S functions as a tumor promoter by abolishing RBM4-FL-mediated inhibition of the activity of the SRSF1-mTORC1 signaling pathway. Mechanistically, AURKA disrupts the binding of SRSF3 to YTHDC1, resulting in the inhibition of RBM4-FL production induced by the m6A-YTHDC1-SRSF3 complex. In turn, AURKA recruits hnRNP K to YTHDC1, leading to an m6A-YTHDC1-hnRNP K-dependent exon skipping to produce RBM4-S. Importantly, the small molecules that block AURKA nuclear translocation, reverse the oncogenic splicing of RBM4 and significantly suppress lung tumor progression. Together, our study unveils a previously unappreciated role of nuclear AURKA in m6A reader YTHDC1-dependent oncogenic RNA splicing switch, providing a novel therapeutic route to target nuclear oncogenic events.

Abstract. Warfarin is a commonly used oral anticoagulant. Patients with artificial valve replacement, atrial fibrillation, pulmonary embolism, deep vein thrombosis, and other diseases require long-term anticoagulant oral treatment with warfarin. As warfarin exhibits prompt action with long maintenance time, it has become a key drug for the treatment of patients at risk of developing thrombosis or thromboembolism. Warfarin is a bican coumarin anticoagulant, that exhibits competitive action against vitamin K as its mechanism of action, thereby inhibiting the synthesis of coagulation factors—predominantly the vitamin K-dependent coagulation factors II, VII, IX, and X—in hepatocytes. Long-term warfarin is known to significantly increase the risk of organ bleeding in some patients, while some patients may need to reverse the anticoagulation effect. For instance, patients scheduled for emergency or invasive surgery may require rapid anticoagulation reversal. During such medical circumstances, fresh frozen plasma (FFP) is clinically used for the reversal of excess warfarin-associated anticoagulation, as it contains all the coagulation factors that can alleviate the abnormal blood anticoagulation status in such patients. Accordingly, this article aims to perform an in-depth review of relevant literature on the reversal of warfarin with FFP, and insightful deliberation of the application and efficacy of this clinical intervention.