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Event extraction is one of the important processes in event knowledge graph construction. However, extant event extraction models are confronted with the challenge of handling vague and unfamiliar event trigger words as well as noise that is prevalent in text. To address this issue, this study proposes a joint event extraction model that leverages dynamic attention matching and graph attention network. Specifically, the dynamic attention matching mechanism is employed to identify event nodes that contain text event structure features and to integrate event structure knowledge for constructing event pattern subgraph that correspond to the text, thereby resolving the problem of ambiguous and unknown trigger word classification. To better discriminate between semantic information and event structure information and to mitigate the impact of noise in text, we introduce a graph attention network that integrates event structure features for aggregating feature embedding of node neighbors. Experiment results on the ACE2005 dataset demonstrate that our proposed model attains competitive performance in comparison to existing methods.

As the main type of renal cell carcinoma (RCC), clear cell RCC (ccRCC) is often associated with the deletion or mutation of the von Hippel Lindau (VHL) gene, enhancement of glucose and lipid metabolism, and heterogeneity of the tumor microenvironment. VHL alterations in RCC cells lead to the activation of hypoxia-inducible factors and their downstream target vascular endothelial growth factor, and to the reprogramming of multiple cell death pathways and metabolic weakness, including ferroptosis, which are associated with targeted therapy or immunotherapy. The changes in biological metabolites (e.g., iron and lipids) support ferroptosis as a potential therapeutic strategy for RCC, while iron metabolism and ferroptosis regulation have been examined as anti-RCC agents in numerous studies, and various ferroptosis-related molecules have been shown to be related to the metastasis and prognosis of ccRCC. For example, glutathione peroxidase 4 and glutaminase inhibitors can inhibit pyrimidine synthesis and increase reactive oxygen species levels in VHL-deficient RCC cells. In addition, the release of damage-associated molecular patterns by tumor cells undergoing ferroptosis also mediates antitumor immunity, and immune therapy can synergize with targeted therapy or radiotherapy through ferroptosis. However, Inducing ferroptosis not only suppresses cancer, but also promotes cancer development due to its potential negative effects on anti-cancer immunity. Therefore, ferroptosis and various tumor microenviroment-related molecules may co-occur during the development and treatment of RCC, and further understanding of the interactions, core targets, and related drugs of ferroptosis may provide new combination drug strategies for RCC treatment. Here we summarize the key genes and compounds on ferroptosis and RCC in order to envision future treatment strategies and to provide sufficient information for overcoming RCC resistance through ferroptosis.

Background Reg IV is a member of the regenerating gene family and has been demonstrated to be overexpressed in gastric cancer. However, the functional mechanism of Reg IV in gastric cancer is still unclear. Methods Expression of Reg IV and SOX9 were investigated by immunohistochemistry (IHC) and real-time PCR, and the correlation between the expression of Reg IV and SOX9 was analyzed in gastric cancer tissues. Reg IV expression vectors and a siRNA of Reg IV and SOX9 were transfected into human gastric cancer cells and the protein and mRNA levels of Reg IV and SOX9 were investigated by western blot and real-time PCR. The invasion and migration ability of gastric cancer cells with overexpressed Reg IV and with gene silence of Reg IV and SOX9 were examined by transwell chambers and wound healing assay. Results The Reg IV and SOX9 protein expression levels were both significantly higher in gastric cancer tissues compared with adjacent tissues ( p  = 0.022, p  = 0.003). Reg IV protein expression significantly correlated with tumor invasion depth ( p  <  0.001), but had no significant correlations with age, clinical stage or lymph node metastasis. SOX9 protein expression also had no significant correlations with age, clinical stage, tumor invasion depth or lymph node metastasis. Reg IV transcript expression demonstrated a significant correlation with invasion depth and lymph node metastasis ( p  = 0.005, p  <  0.001) and no significant correlations with age, clinical stage, tumor tissue differentiation or tumor size. SOX9 transcript expression demonstrated a significant correlation with invasion depth and tumor tissue differentiation ( p  = 0.044, p  = 0.007) and no significant correlations with age, clinical stage or tumor size. The Reg IV expression showed a positive correlation with the SOX9 expression ( p  <  0.000, p  = 0.008). Overexpression of Reg IV could upregulate SOX9 expression and promote invasiveness and migration of tumor cells, and silencing of Reg IV could downregulate SOX9 and inhibit invasiveness and migration of tumor cells in MKN-45 and AGS cells. On the other hand, silencing of SOX9 could upregulate Reg IV protein expression. Conclusions Our study demonstrated that Reg IV positively regulates the expression of SOX9 and is involved in tumor cell invasion and migration in gastric cancer.

Nutrient availability, in particular the availability of sugar [carbon (C)] and nitrogen (N), is important for the regulation of plant metabolism and development. In addition to independent utilization of C and N nutrients, plants sense and respond to the balance of C and N nutrients (C/N-nutrient) available to them. High C/low N-nutrient stress has been shown to arrest early post-germinative growth while promoting progression to senescence in Arabidopsis. Although several signaling components of the C/N-nutrient response have been identified, the inclusive molecular basis of plant C/N-nutrient response remains unclear. This proteome analysis evaluated phosphorylation dynamics in response to high C/low N-nutrient stress. Phosphoproteomics under conditions of C/N-nutrient stress showed a global change in the phosphorylation status of proteins, including plasma membrane H -ATPase, carbon and nitrogen metabolic enzymes and signaling proteins such as protein kinases and transcription factors. Further analyses suggested that SNF1-related protein kinase 1 (SnRK1) is involved in primary C/N-nutrient signal mediation via the transcriptional regulation of C/N-regulatory kinases. We also identified a leucine-rich repeat receptor-like kinase with extracellular malectin-like domain, named as LMK1, which was shown to possess cell death induction activity in plant leaves. These results provide important insight into the C/N-nutrient signaling pathways connecting nutrition stress to various cellular and physiological processes in plants.

Background With social transformation, rapid economic development and deepening awareness of psychological health in China, people’s demand for psychological health services is becoming increasingly urgent. A key challenge for Chinese medical organizations is to train enough qualified psychological care nurses. A greater understanding of psychological care competences (PCC) can help in clinical nurse selection, training, and assessment. Objective To develop a PCC framework for Chinese nurses and obtain a consensus on the framework among experts. Methods A descriptive mixed methods study was designed consisting of a literature review and semi-structured interviews followed by three Delphi rounds. The experts ( n  = 16) involved were nurses, nursing managers and educators from nine Chinese provinces with a specific interest in psychological care. Descriptive statistics assisted in data analysis. Results Using the Iceberg Model as a theoretical foundation, five main dimensions and associated subdomains were integrated from 39 chosen articles. The semi-structured interviews with 24 nursing managers and nurses confirmed all of the themes from the literature review while generating new themes, both of which were incorporated into the initial PCC framework. After three Delphi rounds, the experts reached consensus on the PCC framework, including five domains (knowledge, skills, professional ethics, personal traits, internal motivations) and 22 subdomains with connotations. The response rate (RR) values for the three rounds of consultation were 80.00%, 87.50% and 92.86%, the composite reliability (Cr) values were 0.89–0.90, and the Kendall coordination coefficients were 0.155-0.200 ( P  < 0.05). Conclusions On the basis of the Iceberg Model, literature review and qualitative research methods along with Delphi technique were used to develop a scientific and systematic PCC framework. The research methods were feasible and the results were reliable, thereby providing a basis for adopting this framework into nursing education. A formal assessment tool should be developed to test the PCC of nurses in clinical practice.

While genetic evidence shows that the Nav1.7 voltage-gated sodium ion channel is a key regulator of pain, it is unclear exactly how Nav1.7 governs neuronal firing and what biophysical, physiological, and distribution properties of a pharmacological Nav1.7 inhibitor are required to produce analgesia. Here we characterize a series of aminotriazine inhibitors of Nav1.7 in vitro and in rodent models of pain and test the effects of the previously reported \"compound 52\" aminotriazine inhibitor on the spiking properties of nociceptors in vivo. Multiple aminotriazines, including some with low terminal brain to plasma concentration ratios, showed analgesic efficacy in the formalin model of pain. Effective concentrations were consistent with the in vitro potency as measured on partially-inactivated Nav1.7 but were far below concentrations required to inhibit non-inactivated Nav1.7. Compound 52 also reversed thermal hyperalgesia in the complete Freund's adjuvant (CFA) model of pain. To study neuronal mechanisms, electrophysiological recordings were made in vivo from single nociceptive fibers from the rat tibial nerve one day after CFA injection. Compound 52 reduced the spontaneous firing of C-fiber nociceptors from approximately 0.7 Hz to 0.2 Hz and decreased the number of action potentials evoked by suprathreshold tactile and heat stimuli. It did not, however, appreciably alter the C-fiber thresholds for response to tactile or thermal stimuli. Surprisingly, compound 52 did not affect spontaneous activity or evoked responses of Aδ-fiber nociceptors. Results suggest that inhibition of inactivated states of TTX-S channels, mostly likely Nav1.7, in the peripheral nervous system produces analgesia by regulating the spontaneous discharge of C-fiber nociceptors.

Background: Cutaneous immune‐related adverse events (cirAEs) represent a prevalent manifestation of adverse reactions linked to immune checkpoint inhibitors (ICIs) therapy, substantially affecting patients’ quality of life. Objective: To describe the symptomatic experience of cirAEs in patients with cancer receiving ICIs. Design: Qualitative interviews on experiences were conducted from the perspective of patients with cancer. Methods: A purposive sample of 18 patients with cirAEs participated in this semistructured interview. Transcripts were entered into Nvivo 11.0. Qualitative content analysis was used to analyze the data for significant statements and phrases, which were organized into themes and subthemes. Results: Three main themes were identified in the data: (i) multiple emotions coexist, affecting the quality of life; (ii) insufficient coping capacity for cirAEs management; and (iii) exploring needs and expectations for management with cirAEs. Conclusions: The results of this study enable healthcare providers to better understand and empathize with the patient’s experience, to truly practice the essence of patient‐centered care, and to provide a basis for the development of standardized symptom management programs in the future. Implications for Clinical Practice: To strengthen patient education by clarifying knowledge of cirAEs and providing evidence‐based coping strategies, formulate personalized management plans supported by multidisciplinary collaboration when necessary, establish standardized symptom management protocols incorporating regular monitoring and dynamic strategy adjustments, and promote patient participation in decision‐making while building support networks to enhance self‐efficacy, thereby laying the foundation for future standardized management protocols through patient‐centered integrated management approaches.

Plants are able to sense and mediate the balance between carbon (C) and nitrogen (N) nutrient availability to optimize metabolism and growth, described as the C/N response. To clarify the C/N signalling mechanism, C/N-insensitive plants were obtained from an Arabidopsis FOX hunting population, which over-expresses full-length cDNAs for individuals. The resulting cni2-D (carbon/nitrogen insensitive 2-dominant) plant was found to overcome the post-germination growth checkpoint and to expand green cotyledons in disrupted high C/low N stress conditions. The CNI2 gene encodes ABI1, a phosphatase type 2C protein, which negatively regulates abscisic acid (ABA) signal transduction. Over-expressors of ABI1 were found to be insensitive to disrupted C/N stress, whereas the loss-of function mutant abi1-2 was hypersensitive, suggesting that ABI1 plays an essential role in the plant C/N response. By contrast, the C/N-dependent growth phenotype observed in wild-type plants was not associated with endogenous ABA content. Accordingly, the ABA-insensitive mutant abi1-1, which could not bind to the ABA–ABA receptor complex, was not insensitive and restored normal sensitivity to high C/low N stress. The canonical ABA signalling mutants abi4 and abi5 were also sensitive to disrupted C/N stress. Further gene expression analysis demonstrated that several genes in the SnRK2s and SnRK1s pathways are transcriptionally affected by high C/low N stress in wild-type plants regardless of the lack of increased endogenous ABA contents, whereas the expression of these genes were significantly suppressed in ABI1 over-expressors. Taken together, these results suggest direct cross-talk between C/N and non-canonical ABA signalling pathways, regulated by ABI1, in plants.

The Chinese Loess Plateau (CLP) in North China is an important terrestrial archive that witnessed the environmental changes and mammal and early human evolution in Asia over the past 2.6 Ma. Establishing precise ages for the Pleistocene faunas on the CLP is critical for better understanding of these environmental, biological, and archaeological issues. Here we report a new magnetostratigraphic record that places age constraints on the Linyi Fauna on the southeastern CLP. Our investigated 170-m-thick Linyi section mainly consists of two portions: (1) an overlying eolian Quaternary loess-paleosol sequence and (2) underlying fluvial-lacustrine sand and silty clay. Paleomagnetic results suggest that the composite section records the Brunhes chron, Jaramillo and Olduvai subchrons, and successive reverse polarity portions of the intervening Matuyama chron. The Linyi Fauna is located between Jaramillo and Olduvai subchrons in the fluvial-lacustrine interval, with an estimated age of ~1.5–1.6 Ma. Combining previously dated faunas, we establish a Pleistocene magnetochronology spanning from 2.54 to 0.65 Ma for the faunas on the CLP.