Epigenomic, transcriptomic and proteomic characterizations of reference samples.

A variety of newly developed next-generation sequencing technologies are making their way rapidly into the research and clinical applications, for which accuracy and cross-lab reproducibility are critical, and reference standards are much needed. Our previous multicenter studies under the SEQC-2 umbrella using a breast cancer cell line with paired B-cell line have produced a large amount of different genomic data including whole genome sequencing (Illumina, PacBio, Nanopore), HiC, and scRNA-seq with detailed analyses on somatic mutations, single-nucleotide variations (SNVs), and structural variations (SVs). However, there is still a lack of well-characterized reference materials which include epigenomic and proteomic data. Here we further performed ATAC-seq, Methyl-seq, RNA-seq, and proteomic analyses and provided a comprehensive catalog of the epigenomic landscape, which overlapped with the transcriptomes and proteomes for the two cell lines. We identified >7,700 peptide isoforms, where the majority (95%) of the genes had a single peptide isoform. Protein expression of the transcripts overlapping CGIs were much higher than the protein expression of the non-CGI transcripts in both cell lines. We further demonstrated the evidence that certain SNVs were incorporated into mutated peptides. We observed that open chromatin regions had low methylation which were largely regulated by CG density, where CG-rich regions had more accessible chromatin, low methylation, and higher gene and protein expression. The CG-poor regions had higher repressive epigenetic regulations (higher DNA methylation) and less open chromatin, resulting in a cell line specific methylation and gene expression patterns. Our studies provide well-defined reference materials consisting of two cell lines with genomic, epigenomic, transcriptomic, scRNA-seq and proteomic characterizations which can serve as standards for validating and benchmarking not only on various omics assays, but also on bioinformatics methods. It will be a valuable resource for both research and clinical communities.

Association between toxicity-index of diquat and in-hospital mortality in patients with acute diquat poisoning: a retrospective cohort study.

BackgroundThis study investigates the impact of diquat toxicity levels on in-hospital mortality rates among patients with acute diquat poisoning. It aims to clarify the relationship between diquat toxicity scores and the likelihood of death during hospitalization.MethodsA retrospective cohort study was conducted on 98 individuals with acute diquat poisoning. Data on post-ingestion time, initial diquat plasma concentration, and clinical outcomes were systematically collected for all participants. The toxicity-index of diquat was calculated based on post-ingestion time and initial diquat plasma concentration. Logistic regression analysis was utilized to assess the association between toxicity-index of diquat and in-hospital mortality rates, adjusting for potential confounding variables such as age, comorbidities, and treatment interventions.ResultsThe study found that the overall prevalence of in-hospital mortality was 34.7%, with 58.2% in males. The multivariable-adjusted regression coefficient for in-hospital mortality associated with the toxicity-index was 1.09, with a 95% confidence interval (CI) of 1.01-1.17. Subsequent exploratory subgroup analysis indicated that there were no significant interactions (all P values for interaction were >0.05).ConclusionsThe study found that higher diquat toxicity-index values correlate with increased in-hospital mortality in acute diquat poisoning cases, indicating that the toxicity-index could be a useful biomarker for assessing mortality risk.

Effect of posterior decompression on the spinal cord in thoracic ossification of the posterior longitudinal ligament: A Finite element analysis.

OBJECTIVE: Thoracic ossification of the posterior longitudinal ligament (T-OPLL) causes myelopathy. Although posterior decompression for T-OPLL has shown positive results, patients with kyphotic curvatures often endure poor outcomes. Posterior decompression with fusion (PDF) has demonstrated better results compared to posterior decompression alone. This study aims to evaluate the effects of the posterior procedures for T-OPLL. METHODS: A 3-dimensional finite element model of the C2-T12 spine, created from medical images, was used to develop the following T3-T4 OPLL compression models: an intact model (no surgery), 25% canal occupancy ratio (COR) OPLL (C25 OPLL), a discontinuous 25% COR OPLL (D25 OPLL), a continuous 50% COR OPLL (C50 OPLL), and a discontinuous 50% COR OPLL (D50 OPLL). These models were analyzed to evaluate the effects of posterior decompression (laminectomy: LN) with varied fixation lengths (LN T3-T4, PDF T3-T4, LN T2-T5, and PDF T2-T5) in neutral, flexion, and extension positions. RESULTS: Increased discontinuity in OPLL led to increased stress on the spinal cord. Posterior decompression reduced spinal cord stress in the neutral posture. However, in flexion and extension, spinal cord stress increased for LN T3-T4, LN T2-T5, and PDF T3-T4 compared to the neutral posture. Notably, PDF T2-T5 prevented an increase in spinal cord stress during these motions. CONCLUSIONS: Effective management of intervertebral mobility and the appropriate length of decompression are crucial for addressing the thickness and mobility of T-OPLL.

Monocytes Reprogrammed by 4-PBA Potently Contribute to the Resolution of Inflammation and Atherosclerosis.

BACKGROUND: Chronic inflammation initiated by inflammatory monocytes underlies the pathogenesis of atherosclerosis. However, approaches that can effectively resolve chronic low-grade inflammation targeting monocytes are not readily available. The small chemical compound 4-phenylbutyric acid (4-PBA) exhibits broad anti-inflammatory effects in reducing atherosclerosis. Selective delivery of 4-PBA reprogrammed monocytes may hold novel potential in providing targeted and precision therapeutics for the treatment of atherosclerosis. METHODS: Systems analyses integrating single-cell RNA sequencing and complementary immunologic approaches characterized key resolving characteristics as well as defining markers of reprogrammed monocytes trained by 4-PBA. Molecular mechanisms responsible for monocyte reprogramming were assessed by integrated biochemical and genetic approaches. The intercellular propagation of homeostasis resolution was evaluated by coculture assays with donor monocytes trained by 4-PBA and recipient naive monocytes. The in vivo effects of monocyte resolution and atherosclerosis prevention by 4-PBA were assessed with the high-fat diet-fed ApoE-/- mouse model with IP 4-PBA administration. Furthermore, the selective efficacy of 4-PBA-trained monocytes was examined by IV transfusion of ex vivo trained monocytes by 4-PBA into recipient high-fat diet-fed ApoE-/- mice. RESULTS: In this study, we found that monocytes can be potently reprogrammed by 4-PBA into an immune-resolving state characterized by reduced adhesion and enhanced expression of anti-inflammatory mediator CD24. Mechanistically, 4-PBA reduced the expression of ICAM-1 (intercellular adhesion molecule 1) via reducing peroxisome stress and attenuating SYK (spleen tyrosine kinase)-mTOR (mammalian target of rapamycin) signaling. Concurrently, 4-PBA enhanced the expression of resolving mediator CD24 through promoting PPARγ (peroxisome proliferator-activated receptor γ) neddylation mediated by TOLLIP (toll-interacting protein). 4-PBA-trained monocytes can effectively propagate anti-inflammation activity to neighboring monocytes through CD24. Our data further demonstrated that 4-PBA-trained monocytes effectively reduce atherosclerosis pathogenesis when administered in vivo. CONCLUSIONS: Our study describes a robust and effective approach to generate resolving monocytes, characterizes novel mechanisms for targeted monocyte reprogramming, and offers a precision therapeutics for atherosclerosis based on delivering reprogrammed resolving monocytes.

A synergistic enhancement strategy for mechanical and conductive properties of hydrogels with dual ionically cross-linked κ-carrageenan/poly(sodium acrylate-co-acrylamide) network.

Applying conductive hydrogels in electronic skin, health monitoring, and wearable devices has aroused great research interest. Yet, it remains a significant challenge to prepare conductive hydrogels simultaneously with superior mechanical, self-recovery, and conductivity performance. Herein, a dual ionically cross-linked double network (DN) hydrogel is fabricated based on K+ and Fe3+ ion cross-linked κ-carrageenan (κ-CG) and Fe3+ ion cross-linked poly(sodium acrylate-co-acrylamide) P(AANa-co-AM). Benefiting from the abundance of hydrogen bonds and metal coordination bonds, the conductive hydrogel has excellent mechanical properties (fracture strain up to 1420 %, fracture stress up to 2.30 MPa, and toughness up to 20.63 MJ/m3) and good self-recovery performance (the recovery rate of the toughness can reach 85 % after waiting for 1 h). Meanwhile, due to the introduction of dual metal ions of K+ and Fe3+, the ionic conductivity of conductive hydrogel is up to 1.42 S/m. Furthermore, the hydrogel strain sensor has good sensitivity with a gauge factor (GF) of 2.41 (0-100 %). It can be a wearable sensor that monitors different human motions, such as sit-ups. This work offers a new synergistic strategy for designing a hydrogel strain sensor with high mechanical, self-recovery, and conductive properties.

Isomeric Dimer Acceptors for Stable Organic Solar Cells with over 19% Efficiency.

The strategy of isomerization is known for its simple yet effective role in optimizing molecular configuration and enhancing the power conversion efficiency (PCE) of organic solar cells (OSCs). However, the impact of isomerization on the design of dimer acceptors has been rarely investigated, and the relationship between the chemical structure and optoelectronic property remains unclear. In this study, we designed and synthesized two dimer acceptor isomers named D-TPh and D-TN, which differ in the positional arrangement of their end capping groups. Compared to D-TN, D-TPh exhibited enhanced backbone planarity, elevated lowest unoccupied molecular orbital energy level, and more ordered molecular stacking. Consequently, the OSC device based on PM6:D-TPh achieved a PCE of 19.05%, higher than that (PCE = 18.42%) of the device based on PM6:D-TN. Large-area PM6:D-TPh devices (1 cm²) yielded a PCE of 18.0%. More importantly, the extrapolated T80 lifetime of the PM6:D-TPh device is over 2800 h with MPP tracking under continuous one-sun illumination. These results suggest that isomerization strategy is an effective way to optimize the molecular configuration of dimer acceptors for the fabrication of high-efficiency and stable OSCs.

Stepwise One-Shot Borylation Reactions for Intersecting DABNA Substructures Exhibiting Bright Yellow‒Green Electroluminescence with EQE Beyond 40% and Mild Roll-Off.

Boron/nitrogen (B/N)-doped polycyclic aromatic hydrocarbons (PAHs) with the multiple resonance (MR) effect are promising for organic light-emitting diodes (OLEDs) because of their narrowband emission and thermally activated delayed fluorescence (TADF) characteristics. Nevertheless, exploring the variety of such emitters is challenging because of the tricky and limited synthetic protocols. Herein, we designed a novel B/N-doped PAH, L-DABNA-1, whose backbone (L-DABNA) could not be achieved via conventional routes (e.g., one-pot borylation or one-shot borylation). We successfully synthesized it through stepwise one-shot borylations with precisely introducing decorations. The unique MR backbone with intersecting DABNA substructures sharing an aniline group, avoiding any para-N-π-B motif, allows L-DABNA-1 to maintain narrowband TADF emission while significantly redshifting to the yellow-green region with a reverse intersystem crossing rate (kRISC) of 1.28 × 105 s-1. An L-DABNA-1-based OLED device achieved a maximum external quantum efficiency (EQE) of over 40% and maintained a high EQE of 36.3% at 1000 cd m-2, with a current efficiency reaching ~170 cd A-1. This work not only demonstrated the great potential of stepwise borylations in synthesizing B/N-doped PAH backbones, expanding their chemical space, but also provided a promising pathway for exploring MR-TADF emitters at longer wavelengths.

Association between initial diquat plasma concentration, severity index and in-hospital mortality in patients with acute diquat poisoning: a retrospective cohort study.

BACKGROUND: Since 2016, diquat has replaced paraquat in China, resulting in increased diquat poisoning cases. However, understanding of diquat poisoning is still limited. This study aimed to investigate the relationship between initial diquat plasma concentration, severity index, and in-hospital mortality in acute diquat poisoning cases. METHODS: This retrospective cohort study, conducted from January 2016 to July 2023 in a tertiary care hospital, used univariate logistic regression to examine the link between the initial diquat plasma concentration, severity index, and in-hospital mortality in acute diquat poisoned patients. A receiver operating characteristic curve assessed the predictive value of these parameters for prognosis. RESULTS: Among the 87 participants, the median age was 32 years, 35 (40.2%) were female. The overall mortality rate was 37.9%. Logistic regression analysis revealed that the initial diquat plasma concentration and severity index were associated with increased in-hospital mortality. These factors also effectively predicted the prognosis of acute diquat poisoning, with an area under the receiver operating characteristic curve of 0.851 and an optimal diquat concentration threshold of 2.25 mg/L (sensitivity 90.9%, specificity 74.1%, P < 0.05) and an area under the receiver operating characteristic curve of 0.845 with an optimal cut-off value for the sevity index of 9.1 mg/L*min (sensitivity 97%, specificity 74.1%, P < 0.05). DISCUSSION: Our results are limited by the retrospective design of this study. However, if validated, these results could impact management strategies, especially in East Asia. Further research is needed due to potential confounding factors. CONCLUSIONS: The findings suggest that a higher initial plasma concentration and severity index in patients with acute diquat poisoning were correlated with higher in-hospital mortality. Prospective validation will confirm the predicative value of these findings.

Changes of CD8+CD28- Tregs and Gamma-Delta-T-cells in a Neonate with Intrauterine Cytomegalovirus Infection: A Case Report.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection can lead to a range of adverse outcomes. The majority of cCMV neonates with clinical symptoms are infected postnatally; however, established cases of intrauterine infection are uncommon, resulting in a paucity of reports on clinical findings and lymphocytes expression in CMV-infected neonates. CASE PRESENTATION: We followed a neonate with cCMV infection from the onset of hospitalization to several months of follow-up. This infant was intrauterine CMV-positive in the amniotic fluid of the mother at 21 weeks' gestation and received intravenous ganciclovir infusion and sequential oral valganciclovir after birth. The typical clinical signs manifested in the nervous system, liver, and peripheral blood and were documented during the hospitalizaion period and up to the follow-up visit. Flow cytometry was employed to examine the expression of T cells, their subsets, and the associated cytokines in peripheral blood samples at various time points. The flow data for the cCMV neonate were compared with those of the controls at each time point. Following treatment, clinical symptoms improved and the infant became CMV negative. However, developmental delays occurred later in life. The proportion of CD8+CD28- Tregs in the peripheral blood of the neonate with congenital CMV infection was higher than that in the controls at the three time points. The expression levels of perforin and granzyme B secreted by γδ T cells (Vδ1 and Vδ2 T cells), increased during the course of hospitalization until follow-up and were higher than those in the controls at the three time points. CONCLUSIONS: Despite the alleviation of clinical symptoms, developmental delay in later life remains inevitable in this intrauterine cCMV neonate. CD8+CD28- Tregs and Vδ1 and Vδ2 T cells secreting perforin and granzyme B may be involved in congenital CMV infection, although this hypothesis requires validation in a larger study. This report may contribute to our understanding of the effect of current treatment and the immune status of intrauterine cCMV-infected neonates.

The impact of the nursing work environment on compassion fatigue: The mediating role of general self-efficacy.

AIM: To explore the interplay between the perceived nursing work environment, general self-efficacy, and compassion fatigue among registered nurses in Chinese hospitals. BACKGROUND: Compassion fatigue emerges as a significant occupational stress response globally, with the nursing work environment being a pivotal influencer. There is a knowledge gap in understanding how the nursing work environment and general self-efficacy interrelate to affect compassion fatigue, particularly among Chinese nurses. METHODS: Employing a cross-sectional, descriptive design, this study utilized validated questionnaires to gather data from 7085 nurses across public and private hospitals in China. The analysis focused on assessing the interrelations among the perceived nursing work environment, general self-efficacy, and different dimensions of compassion fatigue. FINDING: More than half (65.67%) of the participants experienced moderate or high burnout levels, with 76.43% experiencing secondary traumatic stress. The lowest rating in the nursing work environment was for nurse/physician collaboration (10 ± 2.07), while general self-efficacy scored higher (27.54 ± 6.26). A positive relationship existed between the work environment and both general self-efficacy and compassion satisfaction, with a negative correlation to burnout and traumatic stress. General self-efficacy was a partial mediator in the link between work environment and compassion fatigue, suggesting that improving the work environment can decrease compassion fatigue by boosting nurses' self-efficacy. CONCLUSION: This study underscores the profound impact of the nursing work environment on compassion fatigue, mediated by general self-efficacy. It highlights the necessity of fostering a supportive work environment to enhance nurses' self-efficacy and overall well-being. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Healthcare managers and institutions must create supportive work environments to reduce compassion fatigue among nurses. This includes professional development programs to enhance self-efficacy and job satisfaction. Policies should address high workloads and inadequate support. Nurse leaders should foster environments that promote psychological well-being, improving outcomes for both nurses and patients. Regular assessments and adjustments of work conditions are essential to maintain a healthy work environment.

Solid-State Electrolytes: Probing Interface Regulation from Multiple Perspectives.

Solid-state electrolytes (SSEs), as the heart of all-solid-state batteries (ASSBs), are recognized as the next-generation energy storage solution, offering high safety, extended cycle life, and superior energy density. SSEs play a pivotal role in ion transport and electron separation. Nonetheless, interface compatibility and stability issues pose significant obstacles to further enhancing ASSB performance. Extensive research has demonstrated that interface control methods can effectively elevate ASSB performance. This review delves into the advancements and recent progress of SSEs in interfacial engineering over the past years. We discuss the detailed effects of various regulation strategies and directions on performance, encompassing enhancing Li+ mobility, reducing energy barriers, immobilizing anions, introducing interlayers, and constructing unique structures. This review offers fresh perspectives on the development of high-performance lithium-metal ASSBs.

Targeting Decidual CD16+ Immune Cells with Exosome-Based Glucocorticoid Nanoparticles for Miscarriage.

Immune dysfunction in early pregnancy including overactivation of cytotoxic CD16+ NK cells and proinflammatory M1 macrophages at the maternal-fetal interface interferes with trophoblast invasion, spiral artery remodeling, and decidualization, potentially leading to miscarriage. Immunosuppressants like glucocorticoids (GCs) are used to regulate the immune microenvironment in clinical treatment, but the lack of safe and efficient tissue-specific drug delivery systems, especially immune cell-specific vectors, limits their widespread clinical application. Here, a previously uncharacterized delivery system is reported, termed GC-Exo-CD16Ab, in which GCs are loaded into purified exosomes derived from human umbilical cord mesenchymal stem cells, and subsequently decorated with antibody CD16Ab. GC-Exo-CD16Ab is biocompatible and has remarkable delivery efficiency toward CD16+ decidual natural killer (NK) cells and CD16+ macrophages in mice. This innovative approach effectively suppresses the cytotoxicity of decidual NK cells, inhibits M1 macrophage polarization, and regulates the decidual microenvironment, thereby enhancing placental and fetal morphology, and ultimately mitigating miscarriage risk in the abortion-prone mice. The developed GC-Exo-CD16Ab provides a feasible platform for precise and tissue-specific therapeutic strategies for miscarriage and pregnancy-related diseases.

Regional quality analysis of the hydrological environment with an improved random forest model based on the chimpanzee algorithm.

High-precision evaluations of water environment quality are highly important for improving the accuracy of early warning systems of regional water pollution risk and improving the regional water environment. This paper employs the chimp optimization algorithm (ChOA) to enhance the traditional random forest model, resulting in the chimp optimization algorithm-random forest (ChOA-RF) water quality assessment model for evaluating the Jiansanjiang area in Heilongjiang Province, China. The results show that the overall water environment in Jiansanjiang has the following characteristics: "The water quality of farms in the northwest is poor, and the quality of groundwater is better than that of surface water." Total nitrogen (TN) and total phosphorus (TP) in surface water and ammonium nitrogen (NH3-N), ferrum (Fe), and manganese (Mn) in groundwater are the main pollutants. The TP and TN in surface water and the NH3-N in groundwater exceeded the relevant standards, likely due to the excessive application of chemical fertilizers, especially nitrogen fertilizers. Additionally, Fe and Mn are harmful native substances. According to these findings, targeted improvement strategies, such as reducing nitrogen fertilizer application, plugging well, and increasing the surface water utilization rate, are proposed. Moreover, the ChOA-RF model is compared with the traditional empirical value model and the particle swarm optimization-random forest (PSO-RF) model. The results show that the ChOA-RF model can effectively reduce the root mean square error and mean absolute percentage error and improve the coefficient of determination. The running time and convergence ability are also better than those of the PSO-RF model, which is a more accurate and efficient machine learning model. The model can be used not only for high-precision evaluation of regional water environment quality but also for other machine learning fields.

Strain-Driven Phase Transitions in Delafossite Cu1-xAxAlO2: A Key to Enhanced Photo(electro)catalytic Performance.

This study investigates the impact of intrinsic strain and phase transitions on the thermodynamic stability and electronic properties of Cu1-xAxAlO2 solid solutions, which are key to their photocatalytic performance. It is demonstrated that Cu1-xAxAlO2 with A = Ag, Au, Pt can form continuous isostructural solid solutions due to relatively small compressive strain, while a substantial increase strain restricts Cu1-xPdxAlO2 to forming only limited solutions. For A = Li, Na, the formation of heterostructural solid solutions is facilitated by structural motif alterations, accommodating significant differences in ionic radii and A-O bond characteristics. Specifically, Cu1-xLixAlO2 exhibits a phase transition at x ≈ 0.333, whereas Cu1-xNaxAlO2 undergoes three distinct phase transitions. Electronic structure analysis indicates that in Cu1-xAxAlO2 (A = Ag, Au), d10-d10 closed-shell interactions dominate, enabling tunable band gaps with varying solubility. Nevertheless, increased intrinsic strain in metal sublattices, as seen in A = Pd and Pt, shifts antibonding states to the Fermi level, inducing a semiconductor-to-metal transition. Experimental evidence confirms that Ag+ ions modulate the band gaps and carrier dynamics in Cu1-xAgxAlO2, with Cu0.75Ag0.25AlO2 exhibiting heightened photoelectrochemical activity and a 38.5-fold enhancement in H2 production rate over CuAlO2. Additionally, the coordination environment changes between alkali metals and O, induced by phase transitions, effectively tune the band edge positions and carrier dynamics of Cu1-xAxAlO2 (A = Li, Na) heterostructural solid solutions. Therefore, 3R-Cu0.97Li0.03AlO2 with asymmetric nonlinear dumbbell O-Cu-O demonstrates the highest photocatalytic H2 production activity, 72.9 times greater than CuAlO2. In contrast, α-Cu1-xAxAlO2 with a smaller CuO6 octahedral splitting energy exhibits increased band gaps, resulting in diminished photocatalytic activity. This research underscores that strain-driven phase transition provides an additional control factor and new mechanism for regulating the photo(electro)catalytic activity of Cu1-xAxAlO2 solid solutions.

Single-nucleus multiomics reveals the disrupted regulatory programs in three brain regions of sporadic early-onset Alzheimer's disease.

Sporadic early-onset Alzheimer's disease (sEOAD) represents a significant but less-studied subtype of Alzheimer's disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type-specific transcriptomic changes and linked candidate cis-regulatory elements (cCREs) across brain regions. We prioritized seven conservative transcription factors in glial cells in multiple brain regions, including RFX4 in astrocytes and IKZF1 in microglia, which are implicated in regulating sEOAD-associated genes. Moreover, we identified the top 25 altered intercellular signaling between glial cells and neurons, highlighting their regulatory potential on gene expression in receiver cells. We reported 38 cCREs linked to sEOAD-associated genes overlapped with late-onset AD risk loci, and sEOAD cCREs enriched in neuropsychiatric disorder risk loci. This atlas helps dissect transcriptional and chromatin dynamics in sEOAD, providing a key resource for AD research.

Exploring factors influencing awareness and knowledge of human papillomavirus in Chinese college students: A cross-sectional study.

Cervical cancer remains a significant health burden in China, characterized by high incidence and mortality rates, which are exacerbated by low Human Papillomavirus (HPV) vaccination coverage, leading to substantial loss of productivity, emotional suffering, and family strain. Understanding factors that influence HPV awareness and knowledge is crucial for developing effective educational strategies. This cross-sectional study, conducted from September to October 2022, involved 2,679 college students from various educational institutions in Jiangsu Province, China. Data were collected via an online questionnaire covering demographics, HPV knowledge, and vaccination behaviors. Statistical analyses, including Chi-square tests and multifactorial logistic regression, were used to identify factors influencing HPV knowledge. The study revealed that while over 90% of students correctly identified HPV's transmission and risks, significant knowledge gaps and misconceptions persist, particularly regarding HPV's association with HIV/AIDS and its treatment. Factors significantly associated with better HPV knowledge included age (22-24 years), female gender, being a medical major, being in a relationship, familiarity with HPV, and participation in sexual education programs. Despite a high willingness to receive the HPV vaccine (91.64%), actual vaccination rates remained low. These findings suggest that while Chinese college students were generally aware of HPV, targeted educational interventions are essential to address knowledge gaps and promote HPV vaccination effectively.

The metabolic network response and tolerance mechanism of Thalassia hemprichii under high sulfide based on widely targeted metabolome and transcriptome.

Costal eutrophication leads to increased sulfide levels in sediments, which has been identified as a major cause of the global decline in seagrass beds. The seagrass Thalassia hemprichii, a dominant tropical species in the Indo-Pacific, is facing a potential threat from sulfide, which can be easily reduced from sulfate in porewater under the influence of global climate change and eutrophication. However, its metabolic response and tolerance mechanisms to high sulfide remain unclear. Thus, the current study investigated the physiological responses and programmed metabolic networks of T. hemprichii through a three-week mesocosm experiment, integrating physiology, stable isotope, widely targeted metabolomics, transcriptomics, and microbial diversity assessments. High sulfide reduced the sediment microbial diversity, while increased sediment sulfate reduced bacterial abundance and δ34S. The exposure to sulfide enhanced root δ34S while decreased leaf δ34S in T. hemprichii. High sulfide was shown to inhibit photosynthesis via damaging PSII, which further reduced ATP production. In response, abundant up-regulated differentially expressed genes in energy metabolism, especially in oxidative phosphorylation, were activated to compensate high energy requirement. High sulfide also promoted autophagy by overexpressing the genes related to phagocytosis and phagolysosome. Meanwhile, metabolomic profiling revealed that the contents of many primary metabolites, such as carbohydrates and amino acids, were reduced in both leaves and roots, likely to provide more energy and synthesize stress-responsive secondary metabolites. Genes related to nitrate reduction and transportation were up-regulated to promote N uptake for sulfide detoxification. High sulfide levels specifically enhanced thiamine in roots, while increased jasmonic acid and flavonoid levels in leaves. The distinct differences in metabolism between roots and leaves might be related to sulfide levels and the growth-defense trade-off. Collectively, our work highlights the specific mechanisms underlying the response and tolerance of T. hemprichii to high sulfide, providing new insights into seagrass strategies for resisting sulfide.

Mediating Role of Evidence-Based Nursing Competence Between Specialist Nurses' Information Literacy and Innovative Behaviour: A Multicentre Cross-Sectional Study.

AIM: To investigate the levels of information literacy, evidence-based nursing competence and innovative behaviour in specialist nurses, determine the impact of information literacy and evidence-based nursing competence on the innovative behaviour of specialist nurses and to analyse the mediating role of evidence-based nursing competence between information literacy and innovative behaviour among specialist nurses. DESIGN: A multicenter cross-sectional design. METHODS: In March 2024, a survey was conducted on 313 specialist nurses in four tertiary Grade A comprehensive hospitals in China. Data collection involved the utilization of general demographic questionnaire, the Information Literacy Questionnaire, the Evidence-Based Nursing Competence Scale and the Nurse Innovation Behaviour Scale. The data were analysed using IBM SPSS26 and Amos28 software. RESULTS: Specialist nurses scored above average in information literacy, evidence-based nursing competence and innovative behaviour. Information literacy significantly positively correlated with innovative behaviour. Evidence-based nursing competence also positively affected innovative behaviour and partially mediated the relationship between information literacy and innovative behaviour. CONCLUSION: This research indicated that specialist nurses exhibited above-average levels of evidence-based nursing competence, information literacy and innovative behaviour. Both information literacy and evidence-based nursing competence positively impacted innovative behaviour, with evidence-based nursing competence playing a significant mediating role between information literacy and innovative behaviour. IMPACT: The findings suggest that nursing managers should focus on enhancing information literacy and evidence-based nursing competence in specialist nurses. Improving these abilities will support the implementation of innovative practices and advance the nursing field. REPORTING METHOD: The research findings were presented in strict accordance with the STROBE statement. PATIENT OR PUBLIC CONTRIBUTION: Not applicable. CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY: It provides reference guidance and theoretical basis for global nursing managers to formulate targeted interventions, so as to effectively enhance the innovative behaviour of specialist nurses.

A potent and selective ENL degrader suppresses oncogenic gene expression and leukemia progression.

The histone acylation reader eleven-nineteen leukemia (ENL) plays a pivotal role in sustaining oncogenesis in acute leukemias, particularly in mixed-lineage leukemia-rearranged (MLL-r) leukemia. ENL relies on its reader domain to recognize histone lysine acylation promoting oncogenic gene expression and leukemia progression. Here, we report the development of MS41, a highly potent and selective von Hippel-Lindau-recruiting ENL degrader that effectively inhibits the growth of ENL-dependent leukemia cells. MS41-induced ENL degradation reduces the chromatin occupancy of ENL-associated transcription elongation machinery, resulting in the suppression of key oncogenic gene expression programs and the activation of differentiation genes. MS41 is well-tolerated in vivo and substantially suppresses leukemia progression in a xenograft mouse model of MLL-r leukemia. Notably, MS41 also induces the degradation of mutant ENL proteins identified in Wilms' tumors. Our findings emphasize the therapeutic potential of pharmacological ENL degradation for treating ENL-dependent cancers, making MS41 not only a valuable chemical probe but also potential anticancer therapeutic for further development.

Preventive Treatment with a CD73 Small Molecule Inhibitor Enhances Immune Surveillance in K-Ras Mutant Pancreatic Intraepithelial Neoplasia.

Immunoprevention is an emerging consideration for solid tumors, including pancreatic ductal adenocarcinoma (PDAC). We and others have shown that Kras mutations in genetic models of spontaneous pancreatic intraepithelial neoplasia (PanIN), which is a precursor to PDAC, results in CD73 expression in the neoplastic epithelium and some populations of infiltrating immune cells, including macrophages and CD8 T cells. CD73 is an ecto-enzyme that converts extracellular adenosine monophosphate (AMP) to adenosine, a critical immune inhibitory molecule in PDAC. We hypothesized inhibition of CD73 would reduce the incidence of PanIN formation and alter the immune microenvironment. To test our hypothesis, we used the KrasG12D; PdxCre1 (KC) genetically engineered mouse (GEM) model and tested the utility of AB-680, a small molecule inhibitor targeting CD73, to inhibit PanIN progression. AB-680, or vehicle control, was administered using oral gavage delivery three days/week at 10mg/kg, beginning when the mice were two months old and lasting three months. We euthanized the mice at five months old. In the KC model, we quantified significantly less pancreatitis, early and advanced PanIN, and quantified a significant increase in M1 macrophages in AB-680-treated mice. Single Cell RNA sequencing (scRNA-seq) of pancreata of AB-680 treated mice revealed increased infiltration of CD4+ T cells, CD8+ T cells, and mature B cells. The scRNA-seq analysis showed that CD73 inhibition reduced M2 macrophages, acinar, and PanIN cell populations. CD73 inhibition enhanced immune surveillance and expanded unique clonotypes of TCR and BCR, indicating that inhibition of CD73 augments adaptive immunity early in the neoplastic microenvironment.