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Abstract Empathy enables understanding and sharing of others’ feelings. Human neuroimaging studies have identified critical brain regions supporting empathy for pain, including the anterior insula (AI), anterior cingulate (ACC), amygdala, and inferior frontal gyrus (IFG). However, to date, the precise spatio-temporal profiles of empathic neural responses and inter-regional communications remain elusive. Here, using intracranial electroencephalography, we investigated electrophysiological signatures of vicarious pain perception. Others’ pain perception induced early increases in high-gamma activity in IFG, beta power increases in ACC, but decreased beta power in AI and amygdala. Vicarious pain perception also altered the beta-band-coordinated coupling between ACC, AI, and amygdala, as well as increased modulation of IFG high-gamma amplitudes by beta phases of amygdala/AI/ACC. We identified a necessary combination of neural features for decoding vicarious pain perception. These spatio-temporally specific regional activities and inter-regional interactions within the empathy network suggest a neurodynamic model of human pain empathy.

Abstract Background Previous studies have demonstrated a strong association between depression and job burnout among healthcare professionals, but the results have been inconsistent, and there is a lack of in-depth exploration of such a relationship among different healthcare professions. The present study aims to investigate the interrelationships between depression and burnout among Chinese healthcare professionals and whether there are differences in the networks of these symptoms between doctors and nurses. Methods The Maslach Burnout Inventory-General Survey and the 2-item Patient Health Questionnaire were employed to assess job burnout and depression among 3,684 healthcare professionals. The translation has been refined to ensure accuracy and academic suitability. Subsequently, network analysis was conducted on 2,244 participants with a higher level of job burnout to identify core symptoms and explore the associations between job burnout and depression. Results The present study showed a network association between lack of interest and pleasure in things and being exhausted from work, excessive tiredness facing work, tendency to collapse at work, and lack of passion for work than before among healthcare professionals, as well as a notable difference in the network association between lack of interest and pleasure in things and lack of passion for work than before between nurses and doctors. Conclusions The depression-burnout network structures differ between doctors and nurses, highlighting the need for targeted intervention measures for both groups.

【Objective】Auxin response factors (ARF) are key transcription factors engaged in the auxin signaling system and play significant roles in plant flower and fruit development, organ morphogenesis, hormone control, and stress responses. The study aims to investigate the biological functions of AsARF gene in Aquilaria sinensis (Lour.) Gilg during the aroma formation process.【Method】The AsARF genes in A. sinensis at genome-wide level were identified and analyzed by bioinformatics approaches. The expression patterns of ARF family members in response to mechanical damage in A. sinensis were revealed through transcriptome data analysis.【Result】Twenty-one AsARF genes were identified at the genome-wide level, and the systematic bioinformatics analysis results showed that these 21 AsARF genes were divided into five groups, with gene sequences within the same group sharing similar gene structures and conserved protein domains, while different groups of AsARF genes exhibited significant variations in the number of exons and introns. Furthermore, cis-acting element analysis revealed that the promoter regions of ARF genes in A. sinensis contained numerous sequences associated with sunlight, anaerobic conditions, gibberellin and other response elements. Gene duplication and collinearity analysis indicated that fragment duplication events played a crucial role in the evolution and expansion of the A. sinensis ARF gene family. Comparing with rice ARF genes, it revealed there was a closer relationship between A. sinensis and Arabidopsis thaliana ARF genes. Additionally, transcriptome data analysis demonstrated a significant decrease in expression levels of AsARF5, AsARF6, AsARF19, AsARF20, and AsARF21 genes in response to mechanical damage in A. sinensis.【Conclusion】The study conducted the first genome-wide identification of the AsARF gene family and offered a comprehensive analysis on their physicochemical properties, systematic evolution, gene structure, conserved protein domains, promoter cis-acting elements, gene duplication, and collinearity. Furthermore, the potential mechanisms of AsARF genes in the aroma formation process of A. sinensis were explored through RNA-seq analysis. The results suggested that some AsARF genes may be involved in the defense and dynamic balance of aroma formation in A. sinensis. These findings provided important theoretical basis for a deeper understanding of the aroma formation mechanism in A. sinensis.

Abstract Objective Although the TyG index is a reliable predictor of insulin resistance (IR) and cardiovascular disease, its effectiveness in predicting major adverse cardiac events in hospitalized acute coronary syndrome (ACS) patients has not been validated in large-scale studies. In this study, we aimed to explore the association between the TyG index and the occurrence of MACEs during hospitalization. Methods We recruited ACS patients from the CCC-ACS (Improving Cardiovascular Care in China-ACS) database and calculated the TyG index using the formula ln(fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). These patients were classified into four groups based on quartiles of the TyG index. The primary endpoint was the occurrence of MACEs during hospitalization, encompassing all-cause mortality, cardiac arrest, myocardial infarction (MI), and stroke. We performed Cox proportional hazards regression analysis to clarify the correlation between the TyG index and the risk of in-hospital MACEs among patients diagnosed with ACS. Additionally, we explored this relationship across various subgroups. Results A total of 101,113 patients were ultimately included, and 2759 in-hospital MACEs were recorded, with 1554 (49.1%) cases of all-cause mortality, 601 (21.8%) cases of cardiac arrest, 251 (9.1%) cases of MI, and 353 (12.8%) cases of stroke. After adjusting for confounders, patients in TyG index quartile groups 3 and 4 showed increased risks of in-hospital MACEs compared to those in quartile group 1 [HR = 1.253, 95% CI 1.121–1.400 and HR = 1.604, 95% CI 1.437–1.791, respectively; p value for trend

Abstract Background The prevalence of burnout, depression, and anxiety among Chinese nurses was 34%, 55.5%, and 41.8% respectively. Mental health problems have significant impacts on their personal well-being, work performance, patient care quality, and the overall healthcare system. Mental health is influenced by factors at multiple levels and their interactions. Methods This was a descriptive qualitative study using phenomenological approach. We recruited a total of 48 nurses from a tertiary hospital in Changsha, Hunan Province, China. Data were collected through focus group interviews. Audio-recorded data were transcribed and inductively analysed. Results Four major themes with 13 subthemes were identified according to the social ecological model: (1) individual-level factors, including personality traits, sleep quality, workplace adaptability, and years of work experience; (2) interpersonal-level factors, encompassing interpersonal support and role conflict; (3) organization-level factors, such as organizational climate, organizational support, career plateau, and job control; and (4) social-level factors, which included compensation packages, social status, and legislative provision and policy. Conclusions Our study provides a nuanced understanding of the multifaceted factors influencing nurses’ mental health. Recognizing the interconnectedness of individual, interpersonal, organizational, and social elements is essential for developing targeted interventions and comprehensive strategies to promote and safeguard the mental well-being of nurses in clinical settings. Trial and protocol registration The larger study was registered with Chinese Clinical Trial Registry: ChiCTR2300072142 (05/06/2023) https://www.chictr.org.cn/showproj.html?proj=192676 . Reporting method This study is reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ).

Abstract Purpose This study investigated the clinicopathological features and surgical procedures of adnexal masses with abdominal pain in pediatric and adolescent patients. Our objective was to better define the clinical presentation of adnexal torsion and to distinguish characteristics of those with torsion and those with an alternate diagnosis. Methods Retrospective cohort study of 212 pediatric and adolescent patients was performed who admitted for abdominal pain and presenting with an adnexal mass between March 2012 to December 2019.Medical records were reviewed for age at operation, including presentation of symptoms and signs; the levels of tumor markers; imaging examinations; pathologic findings; the size of masses; treatment; and outcome. Data management and descriptive analyses were performed using SPSS 26.0. Results The median age of the patients was 14.5 ± 3.6 years at the operation. 126 (59.4%, 126/212) patients presented with an abrupt onset of abdominal pain. A total of 82.1% (174/212) of the participants underwent adnexal conservative surgery. 179 (84.5%, 179/212) patients underwent laparoscopic surgery with an average tumor size of 7.7 ± 3.4 cm, while 33 patients ( 15.6%, 33/212) underwent laparotomy. Rupture of mass and ectopic pregnancy accounted for 7.5% (16/212) and 0.9%(2/212), respectively. Torsion was responsible for 36.8% (78/212) of all patients. Among the patients with torsion, the symptom of nausea and vomiting was more common among girls without torsion (P

ABSTRACT HIV-1 replication is tightly regulated in host cells, and various restriction factors have important roles in inhibiting viral replication. SAMHD1, a well-known restriction factor, suppresses HIV-1 replication by hydrolyzing intracellular dNTPs, thereby limiting the synthesis of viral cDNA in quiescent cells. In this study, we revealed an additional and distinct mechanism of SAMHD1 inhibition during the postviral cDNA synthesis stage. Using immunoprecipitation and mass spectrometry analysis, we demonstrated the interaction between SAMHD1 and MX2/MxB, an interferon-induced antiviral factor that inhibits HIV-1 cDNA nuclear import. The disruption of endogenous MX2 expression significantly weakened the ability of SAMHD1 to inhibit HIV-1. The crucial region within SAMHD1 that binds to MX2 has been identified. Notably, we found that SAMHD1 can act as a sensor that recognizes and binds to the incoming HIV-1 core, subsequently delivering it to the molecular trap formed by MX2, thereby blocking the nuclear entry of the HIV-1 core structure. SAMHD1 mutants unable to recognize the HIV-1 core showed a substantial decrease in antiviral activity. Certain mutations in HIV-1 capsids confer resistance to MX2 inhibition while maintaining susceptibility to suppression by the SAMHD1-MX2 axis. Overall, our study identifies an intriguing antiviral pattern wherein two distinct restriction factors, SAMHD1 and MX2, collaborate to establish an alternative mechanism deviating from their actions. These findings provide valuable insight into the complex immune defense networks against exogenous viral infections and have implications for the development of targeted anti-HIV therapeutics.IMPORTANCEIn contrast to most restriction factors that directly bind to viral components to exert their antiviral effects, SAMHD1, the only known deoxynucleotide triphosphate (dNTP) hydrolase in eukaryotes, indirectly inhibits viral replication in quiescent cells by reducing the pool of dNTP substrates available for viral cDNA synthesis. Our study provides a novel perspective on the antiviral functions of SAMHD1. In addition to its role in dNTP hydrolysis, SAMHD1 cooperates with MX2 to inhibit HIV-1 nuclear import. In this process, SAMHD1 acts as a sensor for incoming HIV-1 cores, detecting and binding to them, before subsequently delivering the complex to the molecular trap formed by MX2, thereby immobilizing the virus. This study not only reveals a new antiviral pathway for SAMHD1 but also identifies a unique collaboration and interaction between two distinct restriction factors, establishing a novel line of defense against HIV-1 infection, which challenges the traditional view of restriction factors acting independently. Overall, our findings further indicate the intricate complexity of the host immune defense network and provide potential targets for promoting host antiviral immune defense.

Abstract To effectively treat osteoarthritis (OA), the existing inflammation must be reduced before the cartilage damage can be repaired; this cannot be achieved with a single type of extracellular vesicles (EVs). Here, a hydrogel complex with logic‐gates function is proposed that can spatiotemporally controlled release two types of EVs: interleukin 10 (IL‐10)+ EVs to promote M2 polarization of macrophage, and SRY‐box transcription factor 9 (SOX9)+ EVs to increase cartilage matrix synthesis. Following dose‐of‐action screening, the dual EVs are loaded into a matrix metalloporoteinase 13 (MMP13)‐sensitive self‐assembled peptide hydrogel (KM13E) and polyethylene glycol diacrylate/gelatin methacryloyl‐hydrogel microspheres (PGE), respectively. These materials are mixed to form a “microspheres‐in‐gel” KM13E@PGE system. In vitro, KM13E@PGE abruptly released IL‐10+ EVs after 3 days and slowly released SOX9+ EVs for more than 30 days. In vivo, KM13E@PGE increased the CD206+ M2 macrophage proportion in the synovial tissue and decreased the tumor necrosis factor‐α and IL‐1β levels. The aggrecan and SOX9 expressions in the cartilage tissues are significantly elevated following inflammation subsidence. This performance is not achieved using anti‐inflammatory or cartilage repair therapy alone. The present study provides an injectable, integrated delivery system with spatiotemporal control release of dual EVs, and may inspire logic‐gates strategies for OA treatment.

Once a mass health crisis breaks out, it causes concern among whole societies. Thus, understanding the individual’s behavior in response to such events is key in government crisis management. From the perspective of social influence theory, this study adopts the empirical research method to collect data information in February 2020 through online survey, with a view to comprehensively describe the individuals’conformity behavior during the COVID-19 outbreak in China. The individual’s conformity behavior and new influencing factors were identified. The results revealed that affective risk perception, cognitive risk perception, and individual risk knowledge had a positive significant impact on normative influence. Affective risk perception and individual risk knowledge had a positive significant on informative influence. Cognitive risk perception did not significantly impact informative influence. Informative influence and normative influence had a positive effect on conformity behavior. These results have significant implications for the management behavior of the government.

Deciphering the functional effects of noncoding genetic variants stands as a fundamental challenge in human genetics. Traditional approaches, such as Genome-Wide Association Studies (GWAS), Transcriptome-Wide Association Studies (TWAS), and Quantitative Trait Loci (QTL) studies, are constrained by obscured the underlying molecular-level mechanisms, making it challenging to unravel the genetic basis of complex traits. The advent of Next-Generation Sequencing (NGS) technologies has enabled context-specific genome-wide measurements, encompassing gene expression, chromatin accessibility, epigenetic marks, and transcription factor binding sites, to be obtained across diverse cell types and tissues, paving the way for decoding genetic variation effects directly from DNA sequences only. The de novo predictions of functional effects are pivotal for enhancing our comprehension of transcriptional regulation and its disruptions caused by the plethora of noncoding genetic variants linked to human diseases and traits. This review provides a systematic overview of the state-of-the-art models and algorithms for genetic variant effect predictions, including traditional sequence-based models, Deep Learning models, and the cutting-edge Foundation Models. It delves into the ongoing challenges and prospective directions, presenting an in-depth perspective on contemporary developments in this domain.

Crustacyanin (CRCN), a family of lipocalin proteins specific to crustaceans, was primarily found in the exoskeleton of crustaceans. By binding with astaxanthin to form the astaxanthin-binding protein complex, it resets the proton at the end of astaxanthin and modifies the acidic site in astaxanthin, thereby regulating crustacean shell color. In addition to regulating shell colors, crustacyanin is involved in the transport of small molecule lipids such as steroid hormones and pheromones and has important biological functions in moult growth, gonadal and nervous system development, resistance to heavy metal lipid metabolism, and hypoxic stress. It was first discovered that the pigment in the blue shell of lobster could be extracted with ammonium chloride via a complex combination of organic bases and lipid pigments. It was later proposed that the pigment was a combination of astaxanthin and multimeric protein complex known as α-CRCN. This complex is composed of an octomer of dimeric β-CRCN subunits, with this dimer formed by two types of CRCN A and C in association with two astaxanthin molecules. Natural crustacyanins are all α-CRCN, comprising a total of 16 molecules. Procambarus clarkii, a member of the order Crustacea (Decapoda, Crayfish), is native to North America and is an important freshwater crustacean in China. It had been established that P. clarkii is susceptible to low oxygen stress during the culture process. The low oxygen environment inhibits the metabolic rate of P. clarkii, leading to increased susceptibility to pathogens; therefore, the ability of P. clarkii to tolerate and physiologically regulate stress due to other environmental factors was also affected, which can lead to irreversible damage and even death in severe cases. To understand the role of crustacyanin-like genes in gonadal development and hypoxic-reoxygenation stress in P. clarkii, a cDNA sequence of the PcCRCN-L gene was isolated from the hepatopancreas of this organism. The structural characteristics and evolutionary patterns of the PcCRCN-L gene were analyzed, and the expression characteristics of the PcCRCN-L gene in different tissues and gonad development stages were investigated. The expression response pattern of PcCRCN-L under hypoxic-reoxygenation stress was investigated. The DNA sequence of the PcCRCN-L gene was 6 130 bp long and located on chromosome 12 of the P. clarkii genome. The cDNA sequence was 2 700 bp, and its open reading frame (ORF) length was 1 587 bp. It contained five exons and four introns, encoded 528 amino acid residues, had a theoretical isoelectric point of 5.71 and a relative molecular weight of 55 613.55, and was a hydrophilic protein. The intron/exon splicing pattern was in accordance with the GT-AG rule. The PcCRCN-L protein had a complete lipocalin domain, which included the typical sequences G-X-W of conserved region Ⅰ (SCR1), T-D-Y of conserved region Ⅱ (SCR2), and arginine R of conserved region Ⅲ (SCR3). The results of multiple sequence alignments and phylogenetic analyses showed that PcCRCN-L, as well as the crustacyanin A and crustacyanin C subgroups, were separately clustered into a branch. The expression characteristics of the PcCRCN-L gene in different tissues showed that PcCRCN-L was expressed in all the tissues; however, the highest expression level was found in the hepatopancreas. The expression trend of the PcCRCN-L gene in the ovary and the hepatopancreas was similar in different stages of gonadal development. The expression level of the PcCRCN-L gene was significantly decreased in stages Ⅰ~Ⅱof ovarian development (P < 0.05), but no significant difference was found in stages Ⅱ~Ⅴ (P > 0.05). The expression of the PcCRCN-L gene was significantly decreased under hypoxia stress for 1 h (P < 0.05), but there was no significant difference between hypoxia stress for 1 h and hypoxia stress for 6 h. After reoxygenation for 1 h, the expression of the PcCRCN-L gene was significantly up-regulated (P < 0.05). Compared with reoxygenation for 1 h, the expression of the PcCRCN-L gene was significantly increased at 12 h (P < 0.05). The results showed that PcCRCN-L should be closely involved in the regulation of gonadal development and hypoxia-reoxygenation stress in P. clarkii.

Abstract Objective PD-L1, a target of immune checkpoint blockade, has been proven to take the role of an oncogene in most human tumors. However, the role of PD-L1 in human pan-cancers has not yet been fully investigated. Materials and methods Pan-cancer analysis was conducted to analyze expression, genetic alterations, prognosis analysis, and immunological characteristics of PD-L1. Estimating the correlation between PD-L1 expression and survival involved using pooled odds ratios and hazard ratios with 95% CI. The Kaplan–Meier (K-M) technique, COX analysis, and receiver operating characteristic (ROC) curves were applied to the survival analysis. Additionally, we investigated the relationships between PD-L1 and microsatellite instability (MSI), tumor mutational burden (TMB), DNA methyltransferases (DNMTs), the associated genes of mismatch repair (MMR), and immune checkpoint biomarkers using Spearman's correlation analysis. Also, immunohistochemical analysis and qRT-PCR were employed in evaluating PD-L1’s protein and mRNA expression in pan-caner. Results PD-L1 showed abnormal mRNA and protein expression in a variety of cancers and predicted prognosis in cancer patients. Furthermore, across a variety of cancer types, the aberrant PD-L1 expression was connected to the MSI, MMR, TMB, drug sensitivity, and tumor immune microenvironment (TIME). Moreover, PD-L1 was significantly correlated with infiltrating levels of immune cells (T cell CD8 + , neutrophil, and so on). Conclusion Our study provides a better theoretical basis and guidance for the clinical treatment of PD-L1.

Converting solar energy to electricity efficiently requires an accurate model with well-estimated parameters in a photovoltaic (PV) system. However, identifying parameters for the PV model remains challenging attributed to the nonlinearity and multimodality inherent in diode circuit models. In this paper, we propose a dual-feedback adaptive clone selection algorithm with a golden sine search. The clonal selection algorithm (CSA), known for its inherent diversity maintenance ability, offers an advantage in handling multimodal optimization problems. The critical factor is the cloning operator, particularly the determination of clone size, crucial for balancing exploration and exploitation. To address the conflict between clone size and convergence speed, we introduce a dual feedback adaptive cloning strategy. This strategy considers both the fitness difference between the hypermutated population and the original population and the harmonic mean distance of the population. Additionally, to improve accuracy, we introduce an elite learning strategy based on the golden sine mechanism. The proposed algorithm’s effectiveness is assessed through comprehensive experiments on PV cells and three PV modules, considering both single diode and double diode models, respectively. The experimental results demonstrate that the accuracy of parameter identification achieved by the proposed algorithm exceeds 99.9% for all three types of PV modules. Moreover, we validate the algorithm’s performance using manufacturer’s datasheets with varying irradiations and temperatures. All experiments consistently indicate the stability and effectiveness of the proposed method in accurately identifying the parameters of PV models.

Social groups in various social species are organized with hierarchical structures that shape group dynamics and the nature of within-group interactions. In-group social bonding, exemplified by grooming behaviors among animals and collective rituals and team-building activities in human societies, is recognized as a practical adaptive strategy to foster group harmony and stabilize hierarchical structures in both human and nonhuman animal groups. However, the neurocognitive mechanisms underlying the effects of social bonding on hierarchical groups remain largely unexplored. Here, we conducted simultaneous neural recordings on human participants engaged in-group communications within small hierarchical groups (n = 528, organized into 176 three-person groups) to investigate how social bonding influenced hierarchical interactions and neural synchronizations. We differentiated interpersonal interactions between individuals of different (inter-status) or same (intra-status) social status and observed distinct effects of social bonding on inter-status and intra-status interactions. Specifically, social bonding selectively increased frequent and rapid information exchange and prefrontal neural synchronization for inter-status dyads but not intra-status dyads. Furthermore, social bonding facilitated unidirectional neural alignment from group leader to followers, enabling group leaders to predictively align their prefrontal activity with that of followers. These findings provide insights into how social bonding influences hierarchical dynamics and neural synchronization while highlighting the role of social status in shaping the strength and nature of social bonding experiences in human groups.

BackgroundMultiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system. Currently, the pathological mechanisms of MS are not fully understood, but research has suggested that iron metabolism disorder may be associated with the onset and clinical manifestations of MS.Methods and materialsThe study utilized publicly available databases and bioinformatics techniques for gene expression data analysis, including differential expression analysis, weighted correlation network analysis, gene enrichment analysis, and construction of logistic regression models. Subsequently, Mendelian randomization was used to assess the causal relationship between different iron metabolism markers and MS.ResultsThis study identified IREB2, LAMP2, ISCU, ATP6V1G1, ATP13A2, and SKP1 as genes associated with multiple sclerosis (MS) and iron metabolism, establishing their multi-gene diagnostic value for MS with an AUC of 0.83. Additionally, Mendelian randomization analysis revealed a potential causal relationship between transferrin saturation and MS (p=2.22E-02; OR 95%CI=0.86 (0.75, 0.98)), as well as serum transferrin and MS (p=2.18E-04; OR 95%CI=1.22 (1.10, 1.36)).ConclusionThis study comprehensively explored the relationship between iron metabolism and MS through integrated bioinformatics analysis and Mendelian randomization methods. The findings provide important insights for further research into the role of iron metabolism disorder in the pathogenesis of MS and offer crucial theoretical support for the treatment of MS.

Background: Polyphyllin, a natural compound derived primarily from the Paris genus, manifests its anticancer properties. Extensive research on its therapeutic potential in cancers has been reported. However, there is no systematical analysis of the general aspects of research on polyphyllin by bibliometric analysis. The aim of this study is to visualize emerging trends and hotspots and predict potential research directions in this field. Methods: In this study, we collected relevant research articles from the Web of Science Core Collection Bibliometrics. Using R-bibliometrix, we analyzed the research status, hotspots, frontiers, and development trends of polyphyllin in high-incidence cancers. To conduct a comprehensive visual analysis, CiteSpace and VOSviewer were used for visual analysis of authors, countries, institutions, keywords, and co-cited references within the published articles. Results: A total of 257 articles focusing on the research of polyphyllin in high-incidence cancers were retrieved from the WOSCC database, covering the period from 2005 to 2023. The analysis revealed a consistent increasing trend in annual publications during this timeframe. Notably, China emerged as the most productive country, with Tianjin University leading the institutions. The Journal of Ethnopharmacology stood out as the most prominent journal in this field, while Gao WY emerged as the most prolific author. Polyphyllin VI, polyphyllin II, and polyphyllin VII have emerged as the latest research hotspots. Additionally, the investigation of autophagy and its associated mechanisms has gained significant attention as a novel research direction. Conclusion: This study presents a novel visualization of the research on polyphyllin saponins in the field of highly prevalent cancers using bibliometric analysis. The investigation of polyphyllin D has emerged as a primary focus in this field, with lung cancer, breast cancer, and liver cancer being the key areas of current research. Lastly, polyphyllin saponins show potential application in the field of cancer.

Abstract Background Psychiatric nurses play a crucial role in treating and supporting adolescents with non-suicidal self-injury (NSSI) in China. However, few studies have explored their experiences and challenges. Objectives The aim of this qualitative study was to describe the challenges experienced by psychiatric nurses when working with adolescents having NSSI behaviors. Methods This was a descriptive qualitative study using phenomenological approach. 18 psychiatric nurses from psychiatric wards were recruited from a tertiary hospital from Changsha, Hunan province, China. In-depth interview was performed for each participant collecting information about their feelings and experiences taking care of NSSI adolescents. ATLAS.ti 8 was used to enter data and perform thematic analysis following the six-phased process described by Braun and Clarke. Results Two main themes and five sub-themes were summarized in this study. Nurses experienced both (1) Internal challenges (Lacking knowledge and skills to deal with NSSI adolescents and Feeling hard and stressful working with NSSI adolescents) and (2) External barriers (Unrealistic high expectations from family and schools, Uncooperative parents and Little help from communities and schools). Conclusions Psychiatric nurses had to face with their own negative feelings, insufficient knowledge and skills, alongside with pressures and little help from family, schools and communities when working with NSSI adolescents. Targeted training programs of treating NSSI adolescents and their supporting systems be performed in nurses, furthermore, family, schools and societies should also be raised.

Abstract Objective The purpose of this study was to investigate the combined effect of self-reported sleep durations and physical activity (PA) on all cause and cardiovascular diseases mortality. Methods Twenty-nine thousand fifty-eight participants (48.5% male, median age 49 years) from the National Health and Nutrition Examination Survey cycles 2007 to 2016 were included. We classified sleep duration into five categories (

Abstract Background Struma ovarii (SO) is a rare tumor and may transform into ovarian strumal carcinoid (OSC) and/or malignant struma ovarii (MSO), but the incidence, clinical characteristics, and survival outcomes have not been well defined. Methods We conducted a retrospective study of patients with ovarian strumal diseases treated in the our hospital between 1980 and 2022. Subgroup analyses of SO, OSC, and MSO were subsequently performed. Results A total of 275 cases (2.14%) were identified in a cohort of 12,864 patients with ovarian teratomas, where SO, OSC, and MSO accounted for 83.3%, 12.0%, and 4.7% of cases, respectively. There were no significant differences in age, tumor sizes, elevated tumor markers, and ascites among the three subgroups. At initial treatment, all patients with SO or OSC had FIGO stage I disease except one SO patient presenting metastatic disease, ten patients had MSO confined to the ovary, whereas other three patients had metastatic diseases. Two patients with SO respectively relapsed at peritoneum and anterior mesorectum, while none of the OSC patients presented tumor recurrence or death despite different surgical procedures employed. The 5-year recurrence-free survival rate was 88.9%, and only one death occurred at 9.5 years after diagnosis in patients with MSO. Radioiodine therapy showed satisfactory therapeutic efficacy, but these patients showed poor responses to the chemotherapy. Conclusion 2.14% of ovarian teratoma could be classified as SO, of which 12.0% and 4.7% of SO may transform into OSC and MSO, repsectively. The survival outcomes were excellent even after SO transformed into OSC or MSO. Synopsis SO occupied 2.14% of ovarian teratoma, where 12.0% and 4.7% of SO may transform into OSC and MSO, respectively, and had excellent survival outcomes.

We investigated the effect of melatonin on bisphenol A (BPA)-induced oxidative stress damage in testicular tissue and Leydig cells. Mice were gavaged with 50 mg/kg BPA for 30 days, and concurrently, were injected with melatonin (10 mg/kg and 20 mg/kg). Leydig cells were treated with 10 μmol/L of BPA and melatonin. The morphology and organ index of the testis and epididymis were observed and calculated. The sperm viability and density were determined. The expressions of melatonin receptor 1A and luteinizing hormone receptor, and the levels of malonaldehyde, antioxidant enzymes, glutathione, steroid hormone synthases, aromatase, luteinizing hormone, testosterone, and estradiol were measured. TUNEL assay was utilized to detect testicular cell apoptosis. The administration of melatonin at 20 mg/kg significantly improved the testicular index and epididymis index in mice treated with BPA. Additionally, melatonin promoted the development of seminiferous tubules in the testes. Furthermore, the treatment with 20 mg/kg melatonin significantly increased sperm viability and sperm density in mice, while also promoting the expressions of melatonin receptor 1A and luteinizing hormone receptor in Leydig cells of BPA-treated mice. Significantly, melatonin reduced the level of malonaldehyde in testicular tissue and increased the expression of antioxidant enzymes (superoxide dismutase 1, superoxide dismutase 2, and catalase) as well as the content of glutathione. Moreover, melatonin also reduced the number of apoptotic Leydig cells and spermatogonia, aromatase expression, and estradiol level, while increasing the expression of steroid hormone synthases (steroidogenic acute regulatory protein, cytochrome P450 family 17a1, cytochrome P450 17α-hydroxylase/20-lyase, and, 17β-hydroxysteroid dehydrogenase) and the level of testosterone. Melatonin exhibited significant potential in alleviating testicular oxidative stress damage caused by BPA. These beneficial effects may be attributed to melatonin’s ability to enhance the antioxidant capacity of testicular tissue, promote testosterone synthesis, and reduce testicular cell apoptosis.

Background: The development of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis following viral encephalitis, such as Japanese encephalitis, has received increasing attention in recent years. However, the mechanism of anti-NMDAR antibody production following Japanese encephalitis has not been explored. Methods: A peptide from the Japanese encephalitis virus (JEV), which shares a similar amino acid sequence with GluN1, was identified by sequence comparison. We then explored whether active subcutaneous immunization with the JEV peptide could induce the production of anti-NMDAR antibodies and related pathophysiological and behavioral changes in mice. In addition, a published active immune model of anti-NMDAR encephalitis using a GluN1 peptide was used as the positive control. Results: A 6-amino-acid sequence with 83 % similarity between the envelope protein of the JEV (HGTVVI) and GluN1 (NGTHVI) was identified, and the sequence included the N368/G369 region. Active immunization with the JEV peptide induced a substantial and specific immune response in mice. However, anti-NMDAR antibodies were not detected in the serum of mice immunized with the JEV peptide by ELISA, CBA, and TBA. Moreover, mice immunized with the JEV peptide presented no abnormities related to anti-NMDAR antibodies according to western blotting, patch clamp, and a series of behavioral tests. In addition, active immunization with a recently reported GluN1 peptide failed to induce anti-NMDAR antibody production in mice. Conclusions: In this study, the attempt of active immunization with the JEV peptide to induce the production of anti-NMDAR antibodies via molecular mimicry failed. The pathogenesis of anti-NMDAR encephalitis following Japanese encephalitis remains to be elucidated.

Since they emerged approximately 125 million years ago, flowering plants have evolved to dominate the terrestrial landscape and survive in the most inhospitable environments on earth. At their core, these adaptations have been shaped by changes in numerous, interconnected pathways and genes that collectively give rise to emergent biological phenomena. Linking gene expression to morphological outcomes remains a grand challenge in biology, and new approaches are needed to begin to address this gap. Here, we implemented topological data analysis (TDA) to summarize the high dimensionality and noisiness of gene expression data using lens functions that delineate plant tissue and stress responses. Using this framework, we created a topological representation of the shape of gene expression across plant evolution, development, and environment for the phylogenetically diverse flowering plants. The TDA-based Mapper graphs form a well-defined gradient of tissues from leaves to seeds, or from healthy to stressed samples, depending on the lens function. This suggests that there are distinct and conserved expression patterns across angiosperms that delineate different tissue types or responses to biotic and abiotic stresses. Genes that correlate with the tissue lens function are enriched in central processes such as photosynthetic, growth and development, housekeeping, or stress responses. Together, our results highlight the power of TDA for analyzing complex biological data and reveal a core expression backbone that defines plant form and function.

Epimedium koreanum Nakai, a well-known traditional Chinese medicinal herb, has been widely used to treat osteoporosis and sexual dysfunction for thousands of years. However, due to the decreasing population of East Asian natural resources, yearly output of Epimedium crude herb has been in low supply year by year. In this study, an unusual variety of E. koreanum was discovered in Dunhua, Jilin Province, the northernmost area where this variety was found containing 6 individuals, with three branches that had 27 leaflets, which is much more than the typical leaflet number of 9. Firstly, the novel E. koreanum varety was identified using DNA barcodes. Then, 1171 differentially expressed genes (DEGs) were discovered through parallel RNA-seq analysis between the newly discovered variety and wild type (WT) E. koreanum plant. Furthermore, the results of bioinformatics investigation revealed that 914 positively and 619 negatively correlated genes associated with the number of leaflets. Additionally, based on RNA-Seq and qRT-PCR analysis, two homologous hub TCP genes, which were commonly implicated in plant leaf development, and shown to be up regulated and down regulated in the discovered newly variety, respectively. Thus, our study discovered a novel wild resource for leaf yield rewarding medicinal Epimedium plant breeding, provided insights into the relationship between plant compound leaf formation and gene expression of TCPs transcription factors and other gene candidates, providing bases for creating high yield cultivated Epimedium variety by using further molecular selection and breeding techniques in the future.

Introduction Bleomycin is a crucial and irreplaceable chemotherapy regimen for malignant ovarian germ cell tumours (MOGCTs) but its toxicities especially pulmonary fibrosis have limited the dose of treatment efficacy and decreased the patients’ quality of life (QoL). Nintedanib has been approved for treating progressive fibrosing interstitial lung diseases and has shown potential anti-tumour effects. This study aims to evaluate the effectiveness and safety of nintedanib in the prevention of pulmonary fibrosis induced by bleomycin in MOGCTs patients.Methods and analysis This is a multicentre, randomised, double-blinded, placebo-controlled clinical trial. We will enrol a total of 128 patients who will be randomly assigned to the nintedanib group and placebo group in a 1:1 ratio. Standard bleomycin, etoposide and cisplatin chemotherapy will be given to each MOGCT patient. In addition, patients assigned to nintedanib and the control group will be given oral nintedanib 150 mg two times per day and placebo one tablet two times per day until 1 month after the last cycle of bleomycin therapy, respectively. The primary outcome is the decline of forced vital capacity (FVC). The secondary outcomes are the decline of other pulmonary function indices (forced expiratory volume in 1 s; FVC pred%, carbon monoxide diffusion capacity) and the patients’ QoL, oncological and fertility outcomes. We will use electronic case report forms to record all the participants’ data and SPSS V.27.0/STATA V.16.0/Graphpad Prism V.8.0 to conduct statistical analysis.Ethics and dissemination The Ethics Committee of Peking Union Medical College Hospital has approved the study (I-23PJ400). Written informed consent will be obtained from all participants/guardians. Study results will be submitted to peer-reviewed medical journals for publication and presented at academic conferences.Trial registration number ChiCTR2300070492.

AbstractBackground The prognostic factors for patients with pure ovarian immature teratoma (POIT) and the role of adjuvant chemotherapy in stage IA G2-G3 and IB-IC POIT remains controversial.Methods We conducted a retrospective study of 155 POIT patients treated in our hospital between 2000 and 2022. The recurrence-free survival (RFS), disease-specific survival (DSS), and potential prognostic factors of POIT patients were evaluated. Subgroup analysis was conducted in stage I other than stage IA G1 POIT.Results The median age at diagnosis was 23.0 years (range: 4.0 − 39.0), and 126 (81.3%), 2 (1.3%), 26 (16.8%), and 1 (0.6%) patients had FIGO stage I, stage II, stage III, and stage IV disease, respectively. Twenty-three patients relapsed and five died of the diseases after a median follow-up of 7.6 years, with a 5-year RFS and DSS rate of 86.0% and 97.0%, respectively. Multivariate analysis showed that positive postoperative tumour markers (TM) were the risk factor for recurrence in the overall cohort (hazard ratio [HR] 4.058, 95% CI 1.175 − 14.019, p = 0.027) and subgroup (HR 10.237, 95% CI 2.175 − 48.179, p = 0.003), and FIGO stage II–IV was the only factor for DSS in overall cohort (HR 7.751, 95% CI 1.281 − 46.895, p = 0.026). In 110 patients subjected to subgroup analysis, 29 patients received surveillance without chemotherapy and 81 patients were administered adjuvant chemotherapy. Multivariate analysis revealed active surveillance significantly increased the recurrence rate (5-year RFS of 75.7% vs. 93.6%, HR 7.562, 95% CI 2.441 − 23.424, p

Citrus aurantium L. fruit is a commonly used Chinese medicine whose therapeutic effects tends to be affected by growing conditions. In order to gain insights into the effects of growing location on the cuticular wax composition of C. aurantium L. fruit, we analyzed the differences in the wax composition of its fruits collected from different regions. The findings showed that the cuticular waxes in the fruit peels were mainly composed of fatty acids, which differed quantitatively in the chemical profiles of C. aurantium L. samples from different geographical conditions. Particularly, the concentrations of linoleic acid and stearic acid in the total component content of the fruit peel were above 1%, with a greater level in the geo-authentic samples. Thus, GC–MS-based wax analysis was first used for the chemical characterization and quantification of cuticular waxes, which could be considered as a rapid way for evaluating the quality of medicinal fruits.

Abstract Background The complex hyperglycemic, hypoxic, and reactive oxygen species microenvironment of diabetic wound leads to vascular defects and bacterial growth and current treatment options are relatively limited by their poor efficacy. Results Herein, a functional molecule-mediated copper ions co-assembled strategy was constructed for collaborative treatment of diabetic wounds. Firstly, a functional small molecule 2,5-dimercaptoterephthalic acid (DCA) which has symmetrical carboxyl and sulfhydryl structure, was selected for the first time to assisted co-assembly of copper ions to produce multifunctional nanozymes (Cu-DCA NZs). Secondly, the Cu-DCA NZs have excellent multicatalytic activity, and photothermal response under 808 nm irradiation. In vitro and in vivo experiments showed that it not only could efficiently inhibit bacterial growth though photothermal therapy, but also could catalyze the conversion of intracellular hydrogen peroxide to oxygen which relieves wound hypoxia and improving inflammatory accumulation. More importantly, the slow release of copper ions could accelerate cellular proliferation, migration and angiogenesis, synergistically promote the healing of diabetic wound furtherly. Conclusions The above results indicate that this multifunctional nanozymes Cu-DCA NZs may be a potential nanotherapeutic strategy for diabetic wound healing.

Abstract Objectives To build a nomogram prediction model, assess its predictive ability, and perform a survival decision analysis on patients with muscle‐invasive bladder cancer (MIBC) to study risk factors affecting overall survival (OS). Methods A retrospective analysis was performed on the clinical information of 262 patients with MIBC who underwent radical cystectomy (RC) at the Urology Department of the Second Affiliated Hospital of Kunming Medical University between July 2015 and August 2021. The final model variables that were included were chosen using single‐factor stepwise Cox regression, optimal subset regression, and LASSO regression + cross‐validation with the minimum AIC value. The next step was to do a multivariate Cox regression analysis. The establishment of a nomogram model by fitting and the screening out of independent risk factors impacting the survival of patients with MIBC having radical resection. Receiver Activity Characteristic curves, C‐index, and a calibration plot evaluated the prediction accuracy, validity, and clinical benefit of the model. The 1‐, 3‐, and 5‐year survival rates were then computed for each risk factor using a Kaplan–Meier survival analysis. Results 262 eligible patients in total were enrolled. With a median follow‐up of 32 months, the follow‐up period ranged from 2 to 83 months. 171 cases (65.27%) survived while 91 cases (34.73%) perished. Age (HR = 1.06 [1.04; 1.08], p = 0.001), preoperative hydronephrosis (HR = 0.69 [0.46, 1.05], p = 0.087), T stage (HR = 2.06 [1.09, 3.93], p = 0.027), lymphovascular invasion (LVI, HR = 1.73 [1.12, 2.67], p = 0.013), prognostic nutritional index (PNI, HR = 1.70 [1.09, 2.63], p = 0.018), and neutrophil‐to‐lymphocyte ratio (NLR, HR = 0.52 [0.29, 0.93)], p = 0.026) were independent risk factor for the survival of bladder cancer patients. Create a nomogram based on the aforementioned findings, and then draw the 1‐year, 3‐year, and 5‐year OS receiver operating characteristic curves by the nomogram. The AUC values were 0.811 (95% CI [0.752, 0.869]), 0.814 (95% CI [0.755, 0.873]), and 0.787 (95% CI [0.708, 0.865]), respectively, and the calibration plot matched the predicted value well. The 1‐year, 3‐year, and 5‐year decision curve analyses were higher than the ALL line and None line at threshold values of >5%, 5%–70%, and 20%–70% indicating that the model has good clinical applicability. The calibration plot for the Bootstrap 1000‐time resampled validation model was similar to the actual value. Patients with preoperative combination hydronephrosis, higher T‐stage, combined LVI, low PNI, and high NLR had worse survival, according to Kaplan–Meier survival analysis for each variable. Conclusions This study might conclude that PNI and NLR were separate risk factors that affect a patient's OS after RC for MIBC. The prognosis of bladder cancer may be predicted by PNI and NLR, but additional confirmation in randomized controlled trials is required.

Abstract Objective Ovarian clear cell carcinoma (OCCC) is a distinct entity from epithelial ovarian cancer. The prognosis of advanced and recurrent disease is very poor due to resistance to chemotherapeutic agents. Our aim was to explore the molecular alterations among OCCC patients with different chemotherapeutic responses and to obtain insights into potential biomarkers. Methods Twenty-four OCCC patients were included in this study. The patients were divided into two groups based on the relapse time after the first-line platinum-based chemotherapy: the platinum-sensitive group (PS) and the platinum-resistant group (PR). Gene expression profiling was performed using NanoString nCounter PanCancer Pathways Panel. Results Gene expression analysis comparing PR vs. PS identified 32 differentially expressed genes: 17 upregulated genes and 15 downregulated genes. Most of these genes are involved in the PI3K, MAPK and Cell Cycle-Apoptosis pathways. In particular, eight genes are involved in two or all three pathways. Conclusion The dysregulated genes in the PI3K, MAPK, and Cell Cycle-Apoptosis pathways identified and postulated mechanisms could help to probe biomarkers of OCCC platinum sensitivity, providing a research basis for further exploration of targeted therapy. Graphic abstract

With the emergence of advanced spatial transcriptomic technologies, there has been a surge in research papers dedicated to analyzing spatial transcriptomics data, resulting in significant contributions to our understanding of biology. The initial stage of downstream analysis of spatial transcriptomic data has centered on identifying spatially variable genes (SVGs) or genes expressed with specific spatial patterns across the tissue. SVG detection is an important task since many downstream analyses depend on these selected SVGs. Over the past few years, a plethora of new methods have been proposed for the detection of SVGs, accompanied by numerous innovative concepts and discussions. This article provides a selective review of methods and their practical implementations, offering valuable insights into the current literature in this field.

Human papillomavirus (HPV) is a common sexually transmitted infection. Despite a safe and effective vaccine, uptake continues to be suboptimal. Recently, focus has moved to college campuses in an effort to increase vaccination rates. Little is known about the extent of efforts to reach graduate students on college campuses in the United States and the vaccination rates within this subpopulation. This scoping review assessed the literature on knowledge, attitudes, beliefs, and behaviors about HPV and HPV vaccination among graduate and post-baccalaureate professional students in the United States. This review also aims to identify areas for further research to improve institutions’ abilities to create health programming to increase HPV awareness and HPV vaccination coverage on their campuses. Publications focusing on knowledge, attitudes, beliefs, and behaviors about HPV and HPV vaccination in post-baccalaureate students were included. The systematic review of PubMed, CINAHL, and Embase identified 2562 articles, and 56 articles met all inclusion criteria and were included in this scoping review. A majority of the reviewed studies investigated some combination of knowledge, attitudes, behaviors, and beliefs about HPV and the HPV vaccine in students in professional programs such as medicine. Study design approaches were primarily cross-sectional, utilizing web-based survey distribution methods. HPV vaccination status and HPV screening behaviors were primarily measured through participant self-report. There is limited research investigating post-baccalaureate student knowledge, attitudes, beliefs, and behaviors about HPV and HPV vaccination. There is a need for researchers to further investigate the needs of graduate students to create informative and effective HPV programming.

As a developing country with an agricultural economy as a pillar, Bangladesh is highly vulnerable to adverse effects of climate change, so the generation of high-resolution temperature maps is of great value for Bangladesh to achieve agricultural sustainable development. However, Bangladesh’s weak economy and sparse meteorological stations make it difficult to obtain such maps. In this study, by mining internal features and links inside observed data, we developed an efficient data-driven downscaling technique to generate high spatial-resolution temperature distribution maps of Bangladesh directly from observed temperature data at 34 meteorological stations with irregular distribution. Based on these high-resolution historical temperature maps, we further explored a data-driven forecast technique to generate high-resolution temperature maps of Bangladesh for the period 2025–2035. Since the proposed techniques are very low-cost and fully mine internal links inside irregular-distributed observations, they can support relevant departments of Bangladesh to formulate policies to mitigate and adapt to climate change in a timely manner.

Abstract Background To evaluate the oncological outcomes and the impact of clinicopathological factors on endometrial clear cell carcinoma (ECCC) outcomes. Methods Medical records of patients with primary ECCC treated at our center between 1985 and December 2020 were reviewed. Overall survival (OS) and progression-free survival (PFS) were the endpoints. The Kaplan–Meier method and Cox regression analysis were used. Results In total, 156 patients were included, of whom 59% and 41% had early- and advanced-stage ECCC, respectively. The median age of onset was 61 years, and 80.8% of the patients were postmenopausal. Ninety-two (59%) and 64 (41%) patients had pure ECCC and mixed endometrial carcinoma with clear cell carcinoma (CCC) components, respectively. Mixed pathological components, elevated cancer antigen 125 levels, positive lymphovascular space invasion, deep myometrial invasion, and malignant peritoneal washing cytology (PWC) were more frequently observed in the advanced stage. Thirty-nine patients (25%) experienced relapse and 32 patients (20.5%) died. The 5-year PFS and OS rates for the entire cohort were 72.6% and 79%, respectively. Multivariate analysis showed that advanced-stage disease and positive PWC significantly decreased PFS, while advanced-stage disease and older age (> 61 years) significantly decreased OS. Conclusions ECCC is a rare and aggressive type II endometrial carcinoma that is common in older women and patients with advanced-stage disease. Positive PWC was associated with decreased PFS, although its presence did not influence the stage. Positive PWC, and advanced stage and older age were independent negative prognostic factors.

The hippocampus executes crucial functions from declarative memory to adaptive behaviors associated with cognition and emotion. However, the mechanisms of how morphogenesis and functions along the hippocampal dorsoventral axis are differentiated and integrated are still largely unclear. Here, we show that Nr2f1 and Nr2f2 genes are distinctively expressed in the dorsal and ventral hippocampus, respectively. The loss of Nr2f2 results in ectopic CA1/CA3 domains in the ventral hippocampus. The deficiency of Nr2f1 leads to the failed specification of dorsal CA1, among which there are place cells. The deletion of both Nr2f genes causes almost agenesis of the hippocampus with abnormalities of trisynaptic circuit and adult neurogenesis. Moreover, Nr2f1/2 may cooperate to guarantee appropriate morphogenesis and function of the hippocampus by regulating the Lhx5-Lhx2 axis. Our findings revealed a novel mechanism that Nr2f1 and Nr2f2 converge to govern the differentiation and integration of distinct characteristics of the hippocampus in mice.

Ultraviolet B (UV-B, 280–320 nm) radiation is a major environmental stressor for aquatic organisms on Earth's surface. Its effects on biological systems are well known, but the mechanisms by which organisms respond and adapt to UV-B radiation are still being explored. In this study, we investigated the effects of UV-B radiation on the monogonont rotifer Brachionus asplanchnoidis, focusing on physiological parameters, antioxidant systems, DNA damage, and DNA repair-related molecular mechanism. Our results showed that the LD50 was at 28.53 kJ/m2, indicating strong tolerance to UV-B. However, UV-B radiation caused adverse effects on growth and reproduction, with shortened reproductive period and longevity, decreased fecundity and hatchability, and inhibition of population growth. Biochemical analyses revealed severe oxidative damage and lipid peroxidation, with increased ROS and MDA levels. Activities of antioxidant enzymes were highly induced at low doses but decreased at high doses. DNA damage also occurred in UV-B-exposed rotifers. Furthermore, selected DNA repair-related genes were up-regulated in a dose-dependent manner. These findings provide a comprehensive understanding of the effects of UV-B radiation on rotifers and highlight the importance of considering both ecological and molecular responses in assessing the impact of UV-B radiation on aquatic organisms.

Abstract Background Cell-free DNA (cfDNA) is emerging as a potential biomarker for the detection of ovarian cancer (OC). Recently, we reported a method based upon cfDNA whole-genome sequencing data including the nucleosome distribution (nucleosome footprinting NF), terminal signature sequence (motif), DNA fragmentation (fragment), and copy number variation (CNV).In the present study, we explored whether multiomics early screening technology in cfDNA can be applied for early screening of ovarian cancer. Methods Fifty-nine patients with OC and 100 healthy controls were included in this prospective study. Cell-free DNA was extracted from plasma and analyzed by low-pass whole-genome sequencing. Genomic features were obtained for all samples of the cohort, including copy number variation (CNV), 5’-end motifs, fragmentation profiles, and nucleosome footprinting (NF). An integrated scoring system termed the OC score was developed based on the performance of these four features. Results All four features showed diagnostic potential for OC. Based on the unique genome features of cfDNA, the OC score has high accuracy in distinguishing OC patients from healthy controls (AUC 97.7%; sensitivity 94.7%; specificity 98.0%) as a new comprehensive diagnostic method for OC. The OC score showed a gradual trend from healthy controls to OC patients with different stages, especially for early OC monitoring of concern, which achieved a satisfactory sensitivity (85.7%) at a high specificity. Conclusions This is the first study evaluating the potential of cell-free DNA for the diagnosis of primary OC using multidimensional early screening technology. We present a promising method to increase the accuracy of prediction in patients with OC.

A female phenotype with strip-like gonads, 46, XY pure gonadal dysgenesis (PGD) has a high tendency to develop into gonadal germ cell tumors. We described one patient with 46, XY PGD, who had a gonadal mixed germ cell tumor (GCT) and acute lymphoblastic leukemia (ALL). This is a unique case because two malignancies developed and relapsed in one person with chromosome abnormality, and the patient is the youngest reported so far. There is an association between her GCT and ALL, as the two malignancies may share a common clonal origin and the NRAS mutation likely plays a role in tumor genesis. We organized MDT to formulate a suitable plan of treatment. We completed the surgery and full cycles of chemotherapy for GCT and controlled ALL by chemotherapy and bone marrow transplantation. However, unfortunately, the young life finally ended following a rare transplant rejection. We concluded that ALL likely shares common clonal origin with GCT and that gene mutations may play a role in neoplasia, which requires further exploration. In the face of such complex conditions, we need to balance the treatment of both diseases to prolong survival and improve the patients’ quality of life.

This study aimed to explore the effect of long-term (≥1 year) sleep quality on coronary lesion complexity and cardiovascular prognosis in young acute coronary syndrome (ACS) patients. We consecutively recruited young patients aged from 18 to 44 years old with first-episode ACS and significant epicardial stenosis on coronary angiography from January 2016 to January 2017. Coronary lesion complexity was evaluated based on SYNTAX scores. Long-term sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) (PSQI ≤ 5 and PSQI > 5 groups). The primary endpoints were major adverse cardiovascular events (MACEs). A total of 466 young ACS patients (93.13% male; median age, 41 years) were included. Poor sleepers (PSQI > 5) had higher SYNTAX scores. After adjusting for confounders, PSQI scores (continuous variables, OR: 1.264; 95%CI: 1.166–1.371; p < 0.001) and PSQI grade (binary variable, OR: 3.864; 95%CI: 2.313–6.394; p = 0.001) were significantly associated with an increased risk of complex coronary lesions. During a median follow-up of 74 months, long-term poor sleep quality (PSQI > 5) was significantly associated with an increased risk of MACEs (HR: 4.266; 95%CI: 2.274–8.001; p < 0.001). Long-term poor sleep quality was a risk factor for complex coronary lesions and has adverse effects on cardiovascular prognosis in the young ACS population.

(1) Background: Diabetic cardiomyopathy (DCM) is a unique form of cardiomyopathy that develops as a consequence of diabetes and significantly contributes to heart failure in patients. Esaxerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has demonstrated potential in reducing the incidence of cardiovascular and renal events in individuals with chronic kidney and diabetes disease. However, the exact protective effects of esaxerenone in the context of DCM are still unclear. (2) Methods: The DCM model was successfully induced in mice by administering streptozotocin (55 mg/kg per day) for five consecutive days. After being fed a normal diet for 16 weeks, echocardiography was performed to confirm the successful establishment of the DCM model. Subsequent sequencing and gene expression analysis revealed significant differences in gene expression in the DCM group. These differentially expressed genes were identified as potential targets for DCM. By utilizing the Swiss Target Prediction platform, we employed predictive analysis to identify the potential targets of esaxerenone. A protein–protein-interaction (PPI) network was constructed using the common targets of esaxerenone and DCM. Enrichment analysis was conducted using Metascape. (3) Results: Compared to the control, the diabetic group exhibited impaired cardiac function and myocardial fibrosis. There was a total of 36 common targets, with 5 key targets. Enrichment analysis revealed that the chemokine and PI3K-Akt signaling pathway was considered a crucial pathway. A target-pathway network was established, from which seven key targets were identified. All key targets exhibited good binding characteristics when interacting with esaxerenone. (4) Conclusion: The findings of this study suggest that esaxerenone exhibits a favorable therapeutic effect on DCM, primarily by modulating the chemokine and PI3K-Akt signaling pathway.

For the razor clam Solen grandis, siphonal autotomy and regeneration is a necessary means of facing external stress, which is accompanied by a large amount of energy consumption. To explore the function of the ENO4 gene in the siphonal autotomy and regeneration of S. grandis, the full-length cDNA of the ENO4 in S. grandis was cloned and characterized. The full-length cDNA of SgENO4 was 2,773 base pairs (bp), with an 1,851 bp coding sequence (CDS) encoding 616 amino acids. ​Bioinformatic analysis revealed a slightly lower codon usage bias and a relatively stable nucleotide composition in the SgENO4 sequence. Three conserved motifs were found from the SgENO4 sequence. These conserved motifs vary in length from 14 to 27 amino acids. Moreover, in the siphonal pre-autotomy of razor clams, expression level of the SgENO4 gene was significantly higher in the hepatopancreas and siphonal base than other tissues (P < 0.05). However, the expression of the SgENO4 gene in the siphonal base decreased significantly in the siphonal post-autotomy 7 hours and gradually recovered as the regeneration process continued. ​Linear correlation analysis showed that there was a significant linear correlation between specific weight of siphon and relative expression levels of SgENO4 (R2 = 0.826). RNA interference (RNAi) result showed that the specific weight (the proportion of siphonal weight to body weight) is significantly lower than other groups on the seventh day (P < 0.05), suggesting that interfering with the expression of the SgENO4 gene could inhibit the siphonal regeneration of S. grandis. These results further demonstrate that SgENO4 is a conserved sequence and that it plays a crucial role in the siphonal autotomy and regeneration of S. grandis, advancing further understanding in exploring molecular mechanisms in the siphonal autotomy and regeneration.

Magnetite is one of the common associated minerals of chalcopyrite. However, so far, no studies have elucidated the effect of magnetite on the dissolution behaviors of chalcopyrite. In this paper, the impact of magnetite on the dissolution of chalcopyrite in sulfuric acid was investigated by leaching experiments, electrochemical measurements, XRD, Raman, and FTIR techniques. Results show that the presence of magnetite significantly enhances the dissolution of chalcopyrite. Different additions of magnetite in the leaching system of chalcopyrite contribute to remarkable differences in the redox potentials. When 0.5 g of magnetite was added, the redox potential was maintained in the range of 650–700 mV (vs. SHE) where chalcopyrite was reduced to chalcocite and then oxidized to Cu2+. But for magnetite additions of 1 g and 2 g, the redox potential exceeded the appropriate range for chalcocite formation, so the dissolution of chalcopyrite was dominated by the direct oxidation by Fe3+. Electrochemical measurements verified the existence of the galvanic interaction between magnetite and chalcopyrite, but its effect is much less than that of iron ions on chalcopyrite dissolution. The study suggests that copper extraction of chalcopyrite can be improved by the addition of proper amount of magnetite.

BackgroundRecommendations for the performance of prophylactic central neck dissection (pCND) in patients with clinically node-uninvolved (cN0) papillary thyroid carcinoma (PTC) are not the same. This meta-analysis set out to compare the effectiveness of pCND with total thyroidectomy (TT) in different countries and regions, mainly between western countries and China.MethodsThe electronic databases PubMed, EMBASE, and Cochrane Library were searched for studies published until August 2022. The incidence rate of cervical lymph node metastases (LNMs), locoregional recurrences (LRRs), and postoperative complications were pooled by a random-effects model. Subgroup analyses based on different countries and regions were performed.ResultsEighteen studies involving 5,346 patients were analyzed. In the subgroup of western countries, patients undergoing pCND with TT had a significantly lower LRR rate [69/1,804, 3.82% vs. 139/2,541, 5.47%; odds ratio (OR) = 0.56; 95% CI 0.37–0.85] and a higher rate of temporary hypoparathyroidism (HPT) (316/1,279, 24.71% vs. 194/1,467, 13.22%; OR = 2.23; 95% CI 1.61–3.08) than that of the TT alone group, while no statistically significant difference was found in the rate of permanent HPT and temporary and permanent recurrent laryngeal nerve (RLN) injury. In the Chinese subgroup, the pCND with TT group had a significantly higher incidence rate of both temporary HPT (87/374, 23.26% vs. 36/324, 11.11%; OR = 2.24; 95% CI 1.32–3.81) and permanent HPT (21/374, 5.61% vs. 4/324, 1.23%; OR = 3.58; 95% CI = 1.24–10.37) than that of the TT alone group, while no significant difference was detected in the rate of LRR and temporary and permanent RLN injury.ConclusionCompared with the TT alone for cN0 PTC patients, pCND with TT had a significantly lower LRR rate while having a higher temporary HPT rate in Europe, America, and Australia; however, it showed no significant difference in decreasing LRR rate while having a significantly raised rate of temporary and permanent HPT in China. More population-based results are required to advocate precision medicine in PTC.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022358546.

BackgroundAxillary lymph node dissection (ALND) could be omitted for T1-2 breast cancer patients with 1-2 positive sentinel lymph node (SLN) after breast-conserving surgery when radiation is planned. However, whether ALND could be replaced by radiation in patients with 1-3 positive SLNs when no more non-SLN metastasis were observed after mastectomy are still controversial. The aim of our study was to develop and validate a nomogram for predicting the possibility of non-SLN metastasis in T1–2 and hormone receptor (HR) positive breast cancer patients with 1-3 positive SLNs after mastectomy.MethodsWe retrospectively reviewed and analyzed the data including the basic information, preoperative sonographic characteristics, and pathological features in breast cancer patients with 1-3 positive SLNs in our medical center between Jan 2016 and Dec 2021. The Chi-square, Fisher’s exact test, and t test were used for comparison of categorical and qualitative variables among patients with or without non-SLN metastasis. Univariate and multivariate logistic regression were used to determine the risk factors for non-SLN metastasis. These predictors were used to build the nomogram. The C-index and area under the receiver operating characteristic curve (AUC) was calculated to assess the accuracy of the model.ResultsA total of 49 in 107 (45.8%) patients were identified with non-SLN metastasis. In multivariate analysis, four variables including younger age, lower estrogen receptor (ER) expression, higher histological score, and cortex thickening of the lymph nodes were determined to be significantly associated with non-SLN metastasis. An individualized nomogram was consequently established with a favorable C-index of 0.822 and verified via two internal validation cohorts.ConclusionsThe current study developed a nomogram predicting non-SLN metastasis for T1–2 and HR+ breast cancer with 1–3 positive SLNs after mastectomy and found that patients in the high-risk group exhibited worse relapse-free survival. The novel nomogram may further help surgeons to determine whether ALND could be omitted when 1-3 positive SLNs were observed in T1–2 and HR+ breast cancer patients.

Regulating reactive oxygen species and inflammation are important for treating atherosclerosis. Here, the authors create a cell membrane coated zoledronic acid ceria nanocomposite loaded with probucol for synergistic drug and scavenging nanozyme treatment of atherosclerosis demonstrating application in vivo.

Abstract Background The objective of the study was to analyze the clinical features, treatment, and outcomes of primary vaginal endodermal sinus tumor (EST) in infants and children treated in a tertiary center. Methods Clinical data of patients with pathologically confirmed primary vaginal EST in our hospital from January 1997 to December 2017 were retrospectively reviewed and analyzed. Results A total of 21 patients were included in this study. The median age at diagnosis was 11 months (range, 4–44 months). The most common manifestations were abnormal vaginal bleeding, and a polypoid mass protruding from the vagina. Chemotherapy based on PEB (cisplatin, etoposide, bleomycin) regimen was given, and serum alpha-fetoprotein (AFP) levels dropped to normal levels after 2 to 4 cycles of chemotherapy (median, 2 cycles). After 3 to 13 cycles of chemotherapy, with a median of 5 cycles, 20 patients achieved complete remission (95.2%). The median follow-up time was 80 months (range, 4-281months). At the time of the last follow-up, 19 cases were alive without disease, and the survival rate was 90.5%. Conclusion Vaginal EST is a very rare malignant germ cell tumor and is sensitive to chemotherapy. Conservative surgery combined with PEB chemotherapy is an effective way of treatment. Serum AFP and imaging examinations can monitor the treatment response and recurrence.

Abstract Background Ovarian strumal carcinoid is an extremely rare ovarian malignant tumor with limited data on clinical characteristics and survival outcomes. Methods A retrospective study of 119 patients was conducted, including 98 cases identified from literature review, and their clinical characteristics were investigated. The overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and potential prognostic factors of these patients were also evaluated. Results Lesions of 115 cases were confined to the ovarian while four patients presented with extra-ovarian disease upon initial diagnosis. Surgical treatment options performed in this cohort varied, 5.0% received ovarian cystectomy, 36.1% received unilateral salpingo-oophorectomy (USO), 7.6% received bilateral salpingo-oophorectomy (BSO), 42.0% received hysterectomy with BSO, and 8.4% underwent debulking surgery. Moreover, one patient did not undergo any surgery. No postoperative adjuvant therapy was administered in 89.9% patients, while 7.6% and 2.5% received adjuvant radiotherapy and chemotherapy, of which two patients received combined radiation and chemotherapy. At the final follow-up, 89.1% patients showed no evidence of the disease, and 5.0% were alive with the disease. Only seven deaths occurred, with two attributed to the tumor. The 5-year, 10-year, and 20-year OS rates were 96.0%, 85.0%, and 85.0%, respectively, with a 15-year recurrence rate of 4.4%. The 5-year and 20-year DSS rate were 98.5% and 95.9%. Multivariate Cox regression showed age ≥ 55 years was the only risk factor associated with the OS (P = 0.014, OR 7.988; 95% CI 1.519 – 42.004). However, the univariate and multivariate Cox regression showed no potential risk factor for RFS and DSS. Conclusion Patients with ovarian strumal carcinoid have an excellent prognosis irrespective of the surgical option. Conservative surgery especially USO with individualized adjuvant therapy is recommended.

Coexistent growing teratoma syndrome (GTS) and gliomatosis peritonei (GP) arising during chemotherapy of ovarian immature teratoma (IMT) is extremely rare and can be misdiagnosed as recurrent or progressive disease. We present a 33-year-old woman diagnosed with GTS with synchronous GP during chemotherapy of IMT. She underwent ovarian cystectomy due to ovarian immature teratoma and chemotherapy were administered. The α-fetoprotein (AFP) concentration decreased from 28.7 ng/mL to normal after the second cycle. Four days after the third cycle of chemotherapy, ultrasound and CT revealed an 8-cm mass with negative tumor markers in the pouch of Douglas. An exploratory laparotomy was conducted, and a smooth round cystic-solid 8-cm mass was noted in the pouch of Douglas. Extensive peritoneal seeding glial nodules were also observed on the surface of the uterus, peritoneum, and omentum. The patient underwent a partial omentectomy, intact resection of the tumor, and resection of most of the glial nodules. Postoperative pathology demonstrated a pure mature cystic teratoma component in the mass, as well as diffuse GP involving the uterine serosa, peritoneum, and omentum; this diagnosis of GTS with synchorous GP should be considered in IMT patients with mass newly identified during chemotherapy while tumor markers are normal after treatment.

The flipped classroom is a well-recognized instructional approach that improves learning performance and experience through two sequential phases: pre-class preparation and in-class collaboration. Despite the large differences between the two phases, few studies have explored their separate effects on flipped learning. This study conducted a hierarchical linear regression to investigate how the two sequential phases and their featured behaviors can predict learning performance and experience in a flipped classroom at the undergraduate level. The results indicated that students' pre-class discussion positively predicted their assignment scores to a moderate degree, while the in-class collaboration was negatively correlated with test scores. However, the two phases had a limited impact on students' flipped learning experience. The results also highlight the influence of students’ initial interest and prior achievement on their flipped learning experience. The findings can extend our understanding of the flipped classroom approach and inform its design and implementation in higher education contexts.

Background Aberrant expression of circular RNAs (circRNAs) contributes to the initiation and progression of pulmonary hypertension (PH). Hypoxia‐inducible factor (HIF) is a well‐known modulator of hypoxia‐induced PH. The role and underlying mechanism of circRNAs in the regulation of HIF expression remains elusive. Methods and Results We profiled pulmonary artery transcriptomes using RNA sequencing and screened circRNAs associated with hypoxia treatment. The expression of a novel circRNA, circ_chr11_67292179–67294612 (circ‐myh8), was increased by hypoxia in a time‐dependent manner. We evaluated the effects of circ‐myh8 overexpression by adeno‐associated virus or inhibition by short hairpin RNA on proliferation and cell cycling in mice and pulmonary artery smooth muscle cells. Overexpression of circ‐myh8 promotes PH under normoxia, and disruption of circ‐myh8 by short hairpin RNA mitigates PH in chronic hypoxic mice. Biologically, circ‐myh8 induces the proliferation and cell‐cycle progression of pulmonary artery smooth muscle cells in vivo and in vitro. Mechanistically, RNA pull‐down and RNA immunoprecipitation assays were used to examine the interaction of circRNAs with the binding protein KAT7 (lysine acetyltransferase 7). The acetylation level of lysine 5 of histone H4 in the transcriptional initiation region of HIF1α was determined by chromatin immunoprecipitation assay followed by reverse transcription‐quantitative polymerase chain reaction. Circ‐myh8 acts as a modular scaffold to recruit histone acetyltransferase KAT7 to the promoters of HIF1α, which elicits acetylation of lysine 5 of histone H4 in their promoters. Conclusions Our findings not only reveal the pivotal roles of circ‐myh8 in governing histone modification in anti‐PH treatment but also advocate triggering the circ‐myh8/KAT7/HIF1α pathway to combat PH.