Cross-Kingdom RNA Transport Based on Extracellular Vesicles Provides Innovative Tools for Plant Protection.

RNA interference (RNAi) shows great potential in plant defense against pathogens through RNA-mediated sequence-specific gene silencing. Among RNAi-based plant protection strategies, spray-induced gene silencing (SIGS) is considered a more promising approach because it utilizes the transfer of exogenous RNA between plants and microbes to silence target pathogen genes. The application of nanovesicles significantly enhances RNA stability and delivery efficiency, thereby improving the effectiveness of SIGS and further enhancing plant resistance to diseases and pathogens. This review explores the role of RNAi in plant protection, focusing on the cross-kingdom transport of small RNAs (sRNAs) via extracellular vesicles. It also explores the potential of nanotechnology to further optimize RNA-based plant protection, offering innovative tools and methods in modern plant biotechnology.

Exogenous Application of dsRNA-Inducing Silencing of the Fusarium oxysporum Tup1 Gene and Reducing Its Virulence.

Fusarium oxysporum is a widespread soil-borne fungal pathogen that can infect various plants, causing wilt and root rot diseases. The root rot disease of Atractylodes macrocephala caused by F. oxysporum is among the most serious diseases associated with continuous cropping, significantly hindering its sustainable development. In this study, we aimed to investigate the effect of exogenous application of double-stranded RNA (dsRNA) on silencing the F. oxysporum Tup1 gene to reduce its virulence and to evaluate its potential application in controlling root rot disease in A. macrocephala. The Tup1 gene was amplified from the F. oxysporum genome, and different lengths of Tup1-dsRNA were designed and synthesized. The uptake of dsRNA by the fungus was verified using Tup1-dsRNA labeled with fluorescein, and in vitro dsRNA treatment experiments were conducted to assess its impact on the growth and virulence of F. oxysporum. Additionally, Tup1-dsRNA was applied to the roots of A. macrocephala to evaluate its effectiveness in controlling root rot disease. The experimental results showed that F. oxysporum could effectively uptake exogenously applied Tup1-dsRNA, significantly reducing Tup1 gene expression. All lengths of Tup1-dsRNA inhibited fungal growth and caused morphological changes in the fungal hyphae. Further plant experiments and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) analysis indicated that Tup1-dsRNA treatment significantly reduced the incidence of root rot disease in A. macrocephala, which was supported by the reduction in peroxidase (POD) and catalase (CAT) enzyme activities, malondialdehyde (MDA) content, and proline (Pro) levels in treated root tissues. This study demonstrated that exogenous dsRNA could reduce the virulence of F. oxysporum by silencing the Tup1 gene and effectively mitigate the root rot disease it causes in A. macrocephala. The successful application of Tup1-dsRNA provided strong evidence for the potential of RNA interference (RNAi) technology in plant disease control. Future research could further optimize the design and application of dsRNA to enhance its practical value in agriculture.

StereoSiTE: a framework to spatially and quantitatively profile the cellular neighborhood organized iTME.

BACKGROUND: Spatial transcriptome (ST) technologies are emerging as powerful tools for studying tumor biology. However, existing tools for analyzing ST data are limited, as they mainly rely on algorithms developed for single-cell RNA sequencing data and do not fully utilize the spatial information. While some algorithms have been developed for ST data, they are often designed for specific tasks, lacking a comprehensive analytical framework for leveraging spatial information. RESULTS: In this study, we present StereoSiTE, an analytical framework that combines open-source bioinformatics tools with custom algorithms to accurately infer the functional spatial cell interaction intensity (SCII) within the cellular neighborhood (CN) of interest. We applied StereoSiTE to decode ST datasets from xenograft models and found that the CN efficiently distinguished different cellular contexts, while the SCII analysis provided more precise insights into intercellular interactions by incorporating spatial information. By applying StereoSiTE to multiple samples, we successfully identified a CN region dominated by neutrophils, suggesting their potential role in remodeling the immune tumor microenvironment (iTME) after treatment. Moreover, the SCII analysis within the CN region revealed neutrophil-mediated communication, supported by pathway enrichment, transcription factor regulon activities, and protein-protein interactions. CONCLUSIONS: StereoSiTE represents a promising framework for unraveling the mechanisms underlying treatment response within the iTME by leveraging CN-based tissue domain identification and SCII-inferred spatial intercellular interactions. The software is designed to be scalable, modular, and user-friendly, making it accessible to a wide range of researchers.

Bioinformatics analysis and experimental validation of C6orf120 as a potential prognostic marker and therapeutic target for liver hepatocellular carcinoma.

The C6orf120 gene is a novel gene whose function has not been fully defined. Previous studies have associated it with various liver pathologies, but its specific role in hepatocellular carcinoma (LIHC) remains unclear. This study aimed to investigate the diagnostic and prognostic value of C6orf120 in LIHC, as well as its potential biological functions. In this preliminary research, we utilized data from various databases and bioinformatics tools, including TCGA, GEO, TIMER2, HPA, GEPIA, Linkeomics, Metascape, CIBERSORT, TargetScan, DIANA-microT, RNAinter, and ENCORI, to analyze the expression patterns and mechanisms of C6orf120 in LIHC. Our bioinformatics analysis revealed that C6orf120 is upregulated in LIHC and may serve as a diagnostic and prognostic biomarker. The aberrant expression of C6orf120 in LIHC was further supported by clinical samples and cell lines. In vitro experiments demonstrated that the knockdown of C6orf120 in HepG2 cells significantly reduced migration capacity without affecting proliferation. Additionally, the downregulation of C6orf120 in LIHC cells appeared to inhibit endothelial cell migration and angiogenesis, which are critical in tumorigenesis and development. In conclusion, our findings suggest that C6orf120 could serve as a novel diagnostic and prognostic biomarker for LIHC and is expected to be a prognostic marker and a potential therapeutic target in the clinical management of LIHC.

Clinical efficacy and safety of new compound single tablet antiviral drugs in the treatment of HIV/AIDS.

AIMS: Genvoya, Biktarvy and Dovato are novel single-tablet antiretroviral therapy(ART). The aim of this study is to explore the therapeutic effects of these novel drugs on HIV/AIDS. MAIN METHODS: This retrospective cohort study, conducted at a single center, included a total of 200 HIV-treated patients who transitioned to these new antiretroviral drugs from July 2021 to August 2023. Data were extracted from electronic medical records at Ditan Hospital. The Genvoya group comprised 22 patients, and all subsequent switches in this group were to Biktarvy. The primary HAART group consisted of 178 patients initially treated with a first-line triple Highly Active Antiretroviral Therapy (HAART) regimen during the same period. This group was further subdivided into HAART+Dovato, HAART+Biktarvy, and HAART+Genvoya groups based on the switching regimen. The primary outcomes focused on changes in viral load and immune efficacy, while secondary safety indicators included blood/liver function, lipid parameters, renal function, blood glucose, blood uric acid, etc. KEY FINDINGS: The viral suppression rate was 100 % after the drug change treatment, and CD4+ T cell counts increased significantly across all four groups. Over the 6-month treatment period, there were increases in creatinine (Cr), low-density lipoprotein (LDL), high-density lipoprotein (HDL), erythrocyte count, and glomerular filtration rate (eGFR). Conversely, Alanine transaminase (ALT), Aspartate aminotransferase (AST), C-reactive protein (CRP), albumin (ALB), and blood glucose (Glu) levels decreased. SIGNIFICANCE: Genvoya, Biktarvy and Dovato are recommended for the treatment of HIV/AIDS and have a good safety profile.

Effects of temperature and lactic acid Bacteria additives on the quality and microbial community of wilted alfalfa silage.

This study investigated the influence of different temperatures (35℃ High temperature and average indoor ambient temperature of 25℃) and lactic acid bacterial additives (Lactiplantibacillus plantarym, Lentilactobacillus buchneri, or a combination of Lactiplantibacillus plantarym and Lentilactobacillus buchneri) on the chemical composition, fermentation quality, and microbial community of alfalfa silage feed. After a 60-day ensiling period, a significant interaction between temperature and additives was observed, affecting the dry matter (DM), crude protein (CP), acid detergent fiber (ADF), and neutral detergent fiber (NDF) of the silage feed (p < 0.05). Temperature had a highly significant impact on the pH value of the silage feed (p < 0.0001). However, the effect of temperature on lactic acid, acetic acid, propionic acid, and butyric acid was not significant (p > 0.05), while the inoculation of additives had a significant effect on lactic acid, acetic acid, and butyric acid (p > 0.05). As for the dynamic changes of microbial community after silage, the addition of three kinds of bacteria increased the abundance of lactobacillus. Among all treatment groups, the treatment group using complex bacteria had the best fermentation effect, indicating that the effect of complex lactic acid bacteria was better than that of single bacteria in high temperature fermentation. In summary, this study explained the effects of different temperatures and lactic acid bacterial additives on alfalfa fermentation quality and microbial community, and improved our understanding of the mechanism of alfalfa related silage at high temperatures.

The effect of perineural dexamethasone on nerve injury and recovery of nerve function after surgery: A randomized controlled trial.

Background: While numerous studies have examined the influence of perineural dexamethasone on nerve block duration, its potential impact on postoperative nerve injury has not been adequately addressed. Objective: This study aims to elucidate the effect of perineural dexamethasone on nerve injury and nerve function recovery after surgery. Design: A prospective randomized double-blinded trial. Setting: The First Affiliated Hospital of Chengdu Medical College, Chengdu, China. The study was conducted between 14 June and 30 December 2022. Participants: Patients aged 18 - 80 years, ASA I - II, scheduled for elective orthopedic or burn and plastic surgery. Interventions: Patients were randomized to receive either perineural dexamethasone (D group) or no dexamethasone (ND group). Main outcome measures: Primary outcomes were the incidence and recovery of nerve injury. Secondary outcomes included postoperative pain scores, analgesic consumption, and adverse events. Results: Initial postoperative nerve injury rates were similar between groups (D: 30.4 %, ND: 33.3 %, P > 0.05). At 12 weeks post-discharge, significantly more patients in the ND group recovered from nerve deficits (78.8 % vs 60.3 %; OR = 2.45, 95 % CI = 1.05 - 5.72, P < 0.05). No significant differences were observed in postoperative hyperglycemia or surgical site infection rates. Conclusion: Perineural dexamethasone may impede nerve function recovery, suggesting caution in its use, particularly for patients with pre-existing nerve damage or diabetes. Further research is needed to elucidate the long-term effects of dexamethasone on nerve tissue recovery. Trial registration: chictr.org.cn, ChiCTR2200059424.

Fungal Extracellular Vesicle Proteins with Potential in Biological Interaction.

Extracellular vesicles (EVs) are vesicle-like structures composed of lipid bilayers, which can be divided into apoptotic bodies, microbubbles and exosomes. They are nanoparticles used for the exchange of information between cells. EVs contains many substances, including protein. With the development of proteomics, we know more about the types and functions of protein in vesicles. The potential functions of proteins in the envelope are mainly discussed, including cell wall construction, fungal virulence transmission, signal transmission and redox reactions, which provides a new perspective for studying the interaction mechanism between fungi and other organisms. The fungal protein markers of EVs are also summarized, which provided an exploration tool for studying the mechanism of vesicles. In addition, the possible role of immune protein in the EVs in the treatment of human diseases is also discussed, which provides new ideas for vaccine development.

Changes in food consumption and nutrition intake of rural residents in central China.

Food security and diet diversity is essential to sustainable food system all over the world. As the income of rural residents achieves great increase, the structure of food consumption and food diversification face significant change. Rural residents' food consumption and nutrients intake worth more attention. Chinese government has been striving to achieve sustainable development in rural areas. We conducted this study to explore area-level practices aiming at achieving food and nutrition security in rural China. In order to search for the change principle and main influencing factors of residents' food consumption, three rural areas in Henan Province were selected. According to the data obtained from the Henan Province Bureau of Statistics, changes in food consumption from 2012 to 2021 in three rural areas were analyzed in this study. This study led to the following remarkable results: (1) The per capita consumption of poultry, meat, sugar, and eggs of the three rural residents has increased much more than that of other food items. (2) In the three rural areas, the proportions of grains, vegetables, liquor, and edible oils have decreased overall. The proportions of other categories, such as poultry, meat, and fruits, have increased. (3) The rural residents' per capita nutrition intake has increased remarkably. The results provide some empirical foundation for local government who need suggest that rural residents should control their intake of high-energy food, such as poultry, meat, and sugar. This study has significant policy implication for achieving sustainable goals in rural areas of China.

Role of Forkhead box F1 in the Pathobiology of Pulmonary Arterial Hypertension.

Rationale: Approximately 80% of patients with non-familial pulmonary arterial hypertension (PAH) lack identifiable pathogenic genetic variants. While most genetic studies of PAH have focused on predicted loss-of-function variants, recent approaches have identified ultra-rare missense variants associated with the disease. FOXF1 encodes a highly conserved transcription factor, essential for angiogenesis and vasculogenesis in human and mouse lungs. Objectives: We identified a rare FOXF1 missense coding variant in two unrelated probands with PAH. FOXF1 is an evolutionarily conserved transcription factor required for lung vascular development and vascular integrity. Our aims were to determine the frequency of FOXF1 variants in larger PAH cohorts compared to the general population, study FOXF1 expression in explanted lung tissue from PAH patients versus control (failed-donor) lungs, and define potential downstream targets linked to PAH development. Methods: Three independent, international, multicenter cohorts were analyzed to evaluate the frequency of FOXF1 rare variants. Various composite prediction models assessed the deleteriousness of individual variants. Bulk RNA sequencing datasets from human explanted lung tissues were compared to failed-donor controls to determine FOXF1 expression. Bioinformatic tools identified putative FOXF1 binding targets, which were orthogonally validated using mouse ChIP-seq datasets. Measurements and Main Results: Seven novel or ultra-rare missense coding variants were identified across three patient cohorts in different regions of the FOXF1 gene, including the DNA binding domain. FOXF1 expression was dysregulated in PAH lungs, correlating with disease severity. Histological analysis showed heterogeneous FOXF1 expression, with the lowest levels in phenotypically abnormal endothelial cells within complex vascular lesions in PAH samples. A hybrid bioinformatic approach identified FOXF1 downstream targets potentially involved in PAH pathogenesis, including BMPR2 . Conclusions: Large genomic and transcriptomic datasets suggest that decreased FOXF1 expression or predicted dysfunction is associated with PAH.

Amino polycarboxylic acids-modified abiraterone derivatives as potential injectable anti-prostate cancer agents.

Abiraterone (Abi), an effective cytochrome oxidase P450 C17 (CYP17) inhibitor, inhibits androgen synthesis in testes, adrenal glands, and prostate tumors. However, their low bioavailability and dissolution rate due to their poor solubility and toxic side effects have hindered their clinical applications. In this study, water-soluble and injectable Abi derivatives were developed by introducing amino polycarboxylic acids into Abi, and their antiproliferation effects in vitro, mechanism of action, antitumor activities in vivo, pharmacokinetics, and toxicity were investigated. Compared to Abi, the water-soluble derivative Abi-DTPA exhibited excellent antitumor activity in vitro and in vivo. It decreased cell migration, invasion, and mitochondrial membrane potential. A mechanistic study revealed that it still targeted the CYP17 enzyme and increased the expression levels of apoptosis-related proteins, including cleaved caspase 9, cleaved PARP, and cleaved caspase 3. Abi-DTPA was the main form in the plasma and exhibited lower toxicity after intravenous administration. These findings suggest that Abi-DTPA can be used as a novel injectable anti-prostate cancer agent.

Analyzing the defense response mechanism of Atractylodes macrocephala to Fusarium oxysporum through small RNA and degradome sequencing.

Introduction: Fusarium oxysporum is a significant soil-borne fungal pathogen that affects over 100 plant species, including crucial crops like tomatoes, bananas, cotton, cucumbers, and watermelons, leading to wilting, yellowing, growth inhibition, and ultimately plant death. The root rot disease of A. macrocephala, caused by F. oxysporum, is one of the most serious diseases in continuous cropping, which seriously affects its sustainable development. Methods: In this study, we explored the interaction between A. macrocephala and F. oxysporum through integrated small RNA (sRNA) and degradome sequencing to uncover the microRNA (miRNA)-mediated defense mechanisms. Results: We identified colonization of F. oxysporum in A. macrocephala roots on day 6. Nine sRNA samples were sequenced to examine the dynamic changes in miRNA expression in A. macrocephala infected by F. oxysporum at 0, 6, and 12 days after inoculation. Furthermore, we using degradome sequencing and quantitative real-time PCR (qRT-PCR), validated four miRNA/target regulatory units involved in A. macrocephala-F. oxysporum interactions. Discussion: This study provides new insights into the molecular mechanisms underlying A. macrocephala's early defense against F. oxysporum infection, suggesting directions for enhancing resistance against this pathogen.

Comparison and use of explainable machine learning-based survival models for heart failure patients.

Objective: Explainable machine learning (XAI) was introduced in this study to improve the interpretability, explainability and transparency of the modelling results. The survex package in R was used to interpret and compare two survival models - the Cox proportional hazards regression (coxph) model and the random survival forest (rfsrc) model - and to estimate overall survival (OS) and its determinants in heart failure (HF) patients using these models. Methods: We selected 1159 HF patients hospitalised at the First Affiliated Hospital of Kunming Medical University. First, the performance of the two models was investigated using the C-index, the integrated C/D AUC, and the integrated Brier score. Second, a global explanation of the whole cohort was carried out using the time-dependent variable importance and the partial dependence survival profile. Finally, the SurvSHAP(t) and SurvLIME plots and the ceteris paribus survival profile were used to obtain a local explanation for each patient. Results: By comparing the C-index, the C/D AUC, and the Brier score, this study showed that the model performance of rfsrc was better than coxph. The global explanation of the whole cohort suggests that the C-reactive protein, lg BNP (brain natriuretic peptide), estimated glomerular filtration rate, albumin, age and blood chloride were significant unfavourable predictors of OS in HF patients in both the cxoph and the rfsrc models. By including individual patients in the model, we can provide a local explanation for each patient, which guides the clinician in individualising the patient's treatment. Conclusion: By comparison, we conclude that the model performance of rfsrc is better than that of coxph. These two predictive models, which address not only the whole population but also selected patients, can help clinicians personalise the treatment of each HF patient according to his or her specific situation.

Heparanase accelerates the angiogenesis and inhibits the ferroptosis of p53-mutant non-small cell cancers in VEGF-dependent manner.

The aim of this study is to explore the effects and specific mechanisms of heparanase on angiogenesis and iron deficiency anemia in TP53 mutant cancer. For this purpose, we conducted in vitro cell experiments and in vivo animal experiments respectively. In this study, we first analyzed the differential expression of heparanase in TP53 wild-type and mutant cells, and analyzed its effects on iron removal and angiogenesis in two types of CALU-1 and NCI-H358 cells. Secondly, we validated whether the mechanism of action of heparanase on TP53 mutant cells for iron removal and angiogenesis is related to VEGF. We applied the iron removal agonist erastin and VEGF inhibitor bevacizumab in both in vitro and in vivo experiments to validate the relationship between heparanase and VEGF in the mechanisms of iron removal and angiogenesis. The experimental results show that heparanase is highly expressed in TP53 mutated cancer cells, and has anti-ferroptosis and pro-angiogenic effects. Our experiment also confirmed that the effect of heparanase on TP53 mutant cancer's iron removal and angiogenesis is related to VEGF. In short, heparanase is highly expressed in p53 mutated lung cancer, and the mechanism of ferroptosis tolerance to TP53 mutated cancer is related to VEGF.

Natural Foraging Selection and Gut Microecology of Two Subterranean Rodents from the Eurasian Steppe in China.

As the most abundant group of mammals, rodents possess a very rich ecotype, which makes them ideal for studying the relationship between diet and host gut microecology. Zokors are specialized herbivorous rodents adapted to living underground. Unlike more generalized herbivorous rodents, they feed on the underground parts of grassland plants. There are two species of the genus Myospalax in the Eurasian steppes in China: one is Myospalax psilurus, which inhabits meadow grasslands and forest edge areas, and the other is M. aspalax, which inhabits typical grassland areas. How are the dietary choices of the two species adapted to long-term subterranean life, and what is the relationship of this diet with gut microbes? Are there unique indicator genera for their gut microbial communities? Relevant factors, such as the ability of both species to degrade cellulose, are not yet clear. In this study, we analyzed the gut bacterial communities and diet compositions of two species of zokors using 16S amplicon technology combined with macro-barcoding technology. We found that the diversity of gut microbial bacterial communities in M. psilurus was significantly higher than that in M. aspalax, and that the two species of zokors possessed different gut bacterial indicator genera. Differences in the feeding habits of the two species of zokors stem from food composition rather than diversity. Based on the results of Mantel analyses, the gut bacterial community of M. aspalax showed a significant positive correlation with the creeping-rooted type food, and there was a complementary relationship between the axis root-type-food- and the rhizome-type-food-dominated (containing bulb types and tuberous root types) food groups. Functional prediction based on KEGG found that M. psilurus possessed a stronger degradation ability in the same cellulose degradation pathway. Neutral modeling results show that the gut flora of the M. psilurus has a wider ecological niche compared to that of the M. aspalax. This provides a new perspective for understanding how rodents living underground in grassland areas respond to changes in food conditions.

Effects of exosomes and inflammatory response on tumor: a bibliometrics study and visualization analysis via CiteSpace and VOSviewer.

BACKGROUND: Tumor is a new organism formed by abnormal hyperplasia of local tissue cells under the action of various tumorigenic factors. Inflammation plays a decisive role in inducing tumorigenesis, promoting tumor development, invasion and migration. More and more evidence indicate that exosomes are involved in regulating the formation of tumor microenvironment in the process of proinflammatory carcinogenesis, leading to the stimulation of anti-tumor immune response or systemic immunosuppression, and exosomes play a crucial role in the development of tumor. METHODS: The articles on tumor-derived exosomes and inflammatory responses from January 2005 to January 2024 were collected through Web of Science (WOS), and the inclusion criteria were "Article", "Review Article" and "Early Access". Articles obtained after excluding "Book Chapters", "Editorial Material", "Proceeding Paper", "Meeting Abstract" and "Retracted Publication". Bibliometrics and visualization analysis were carried out on the obtained articles using CiteSpace6.2.R6 and VOSviewer1.6.20. RESULTS: Total of 703 articles were included. The number of published documents showed a fluctuating growth trend year by year. A total of 61 countries have participated in the research on the effects of exosomes and inflammatory responses on tumors, among which China and the United States have the largest influence in this field. The obtained articles have been published in 60 journals around the world, among which PLOS ONE and NAT REV IMMUNOL are the journals with the most published articles and the highest co-citations respectively. The article from French author THERY C was cited the most (202 times). As a major researcher on the basic function of exosomes, THERY C established the gold standard for extraction, separation and identification of exosomes, and found that exosomes promote tumor metastasis through direct regulation of miRNA. Her research has had a huge impact on the field. Keyword co-occurrence analysis indicate that extracellular vesicles, inflammation, cancer, miRNAs, mesenchymal stem cells, drug delivery, gastric cancer and circulating endothelial microparticles are the research hotspot at present stage. The main keywords of the cluster analysis show that extracellular vesicles, human papilloma virus, myeloid cells, tumor macro-environment are the current research hotspots and frontier. The research hotspots have developed over time from the time chart of keywords and clustering, especially after 2016, exosomes have established extensive links with drug delivery, cancer treatment, inflammatory response and other fields. Tumor-derived exosomes stimulate receptor cells to secrete pro-inflammatory cytokines and growth factors, enabling immune and inflammatory cells to perceive the intracellular environment of cancer cells even when cancer cells do not express any tumor-specific antigens. For example, in anoxic environment, cancer cells can secrete exosomes containing pro-inflammatory factors to promote the invasion and metastasis of cancer cells. In the complex tumor microenvironment, both tumor cells and various stromal cells will secrete specific exosomes, and promote the development of tumors through various ways, so that tumor cells have drug resistance, and bring adverse effects on the clinical treatment of tumor patients. MicroRNAs and long noncoding RNA as hot keywords play important roles in regulating and mediating tumor development, and their specificity makes them important biomarkers for cancer prediction and diagnosis. Highlighting word analysis shows that microRNAs secreted by leukemia patients can effectively promote the proliferation of malignant cells and the development of cardiovascular diseases. At the same time, exosomes can induce the secretion of some microRNAs in patients, leading to cardiac repair and regeneration. Therefore, the detection and screening of microRNAs plays a crucial role in predicting the incidence of cardiovascular diseases in patients. CONCLUSION: Exosomes have attracted increasing attention due to their significant heterogeneity and ability to regulate the tumor immune microenvironment. However, tumor cell-derived exosomes accelerate tumor progression by enhancing immunosuppression and inflammation, increasing oxidative stress, and promoting angiogenesis, which may lead to poor prognosis.

Proteogenomic insights into the biology and treatment of pan-melanoma.

Melanoma is one of the most prevalent skin cancers, with high metastatic rates and poor prognosis. Understanding its molecular pathogenesis is crucial for improving its diagnosis and treatment. Integrated analysis of multi-omics data from 207 treatment-naïve melanomas (primary-cutaneous-melanomas (CM, n = 28), primary-acral-melanomas (AM, n = 81), primary-mucosal-melanomas (MM, n = 28), metastatic-melanomas (n = 27), and nevi (n = 43)) provides insights into melanoma biology. Multivariate analysis reveals that PRKDC amplification is a prognostic molecule for melanomas. Further proteogenomic analysis combined with functional experiments reveals that the cis-effect of PRKDC amplification may lead to tumor proliferation through the activation of DNA repair and folate metabolism pathways. Proteome-based stratification of primary melanomas defines three prognosis-related subtypes, namely, the ECM subtype, angiogenesis subtype (with a high metastasis rate), and cell proliferation subtype, which provides an essential framework for the utilization of specific targeted therapies for particular melanoma subtypes. The immune classification identifies three immune subtypes. Further analysis combined with an independent anti-PD-1 treatment cohort reveals that upregulation of the MAPK7-NFKB signaling pathway may facilitate T-cell recruitment and increase the sensitivity of patients to immunotherapy. In contrast, PRKDC may reduce the sensitivity of melanoma patients to immunotherapy by promoting DNA repair in melanoma cells. These results emphasize the clinical value of multi-omics data and have the potential to improve the understanding of melanoma treatment.

HTR1B regulates mitochondrial homeostasis and mitophagy by activating the ERK/ MAPK signalling pathway during human embryonic arrest.

Background: Previous studies have shown that serotonin and its receptors are widely distributed in mammalian reproductive tisssues and play an important role in embryonic development. However, the specific effects of the serotonergic system on embryonic arrest (EA) and the underlying mechanism require further investigation. Methods: Chorionic villi were collected from patients with EA and healthy pregnant women. Western blotting (WB) and immunohistochemistry (IHC) were used to detect serotonin receptor 1B (HTR1B) levels and evaluate mitochondrial function. Additionally, HTR-8/SVneo cells were transfected with an HTR1B overexpression plasmid. Quantitative real-time polymerase chain reaction(qRT-PCR), Cell Counting Kit-8 (CCK-8), and wound healing assays were utilized to evaluate mitophagy level, cell proliferation and cell migration, respectively. Results: We discovered elevated HTR1B levels in the chorionic villi of the patients with EA compared to controls. Concurrently, we observed enhanced levels of nucleus-encoded proteins including mitofilin, succinate dehydrogenase complex subunit A (SDHA), and cytochrome c oxidase subunit 4 (COXIV), along with the mitochondrial fusion protein optic atrophy 1(OPA1), fission proteins mitochondrial fission protein 1(FIS1) and mitochondrial fission factor (MFF) in the EA group. Additionally, there was an excessive mitophagy levels in EA group. Furthermore, a notable activation of mitogen-activated protein kinase (MAPK) signaling pathway proteins including extracellular regulating kinase (ERK), c-Jun N-terminal kinase (JNK), and P38 was observed in the EA group. By overexpressing HTR1B in HTR-8/SVneo cells, we observed a significant reduction in cell proliferation and migration. HTR1B overexpression also caused an increase in levels of SDHA and FIS1, as well as an upregulation of mitophagy. Notably, the ERK inhibitor U0126 effectively mitigated these effects. Conclusion: These findings show that HTR1B influences mitochondrial homeostasis, promoting excessive mitophagy and impairing cell proliferation and migration by activating the MAPK signalling pathway during post-implantation EA. Therefore, HTR1B may serve as a potential therapeutic target for patients with EA.

Effect of oral health education on improving knowledge, attitude, practice, and oral health status of patients with liver cancer: A quasi-experimental study.

PURPOSE: To evaluate the effectiveness of the PRECEDE-PROCEED model (PPM) in helping patients with liver cancer be aware of their knowledge, skills, and abilities in self-oral health behaviors and improve their oral health status. METHODS: This is a quasi-experimental study of 90 patients with liver cancer assigned to an oral health education or a control group. The intervention group was educated with the PRECEDE-PROCEED model. A brief oral scale and the knowledge, attitude, and practice oral health questionnaire were employed to measure the oral health status and cognitive behavioral ability to seek oral health in patients. RESULTS: Among 102 eligible patients, 90 (88.23%) agreed to participate in the present study and were divided to intervention (n = 45) or control (n = 45) groups. After the intervention and one month after discharge, the oral health scores of patients in the Intervention group were lower than those of the control group (P < 0.05). In addition, after the intervention and one month after discharge, the patients in the test group had higher scores on knowledge, beliefs, and behaviors of oral health than the control group (P < 0.05). One month after discharge, the mean knowledge and skills scores were significantly higher in the intervention group than in the control group. CONCLUSIONS: Our findings suggest that oral health education may be a useful health intervention for patients with liver cancer. It may also improve the knowledge and beliefs of liver cancer patients seeking oral health. Larger long-term investigations are necessary to provide more support for these preliminary conclusions.

The mediating role of nutritional care literacy on the relationship between self-directed learning ability and nursing competence.

BACKGROUND: Nurses' nursing competence and nutritional care literacy directly affect patients' health and safety. Self-directed learning ability was pervasive throughout the entire work process of nursing work and was the basis for improving both. However, there are few studies has explored the mechanism from the perspective of nutritional care literacy. The purpose of this study was to analyze the relationship between self-directed learning ability and nursing competence, and to explore the mediating role of nutritional care literacy between self-directed learning and nursing competence among clinical nurses in China. METHODS: A cross-sectional survey was conducted among 805 clinical nurses recruited from seven general hospitals in Hunan Province, China, between January 25 and March 6, 2022. The self-directed learning ability, nutritional care literacy and nursing competence of nurses were evaluated through investigation. A total of 799 questionnaires were received, resulting in an response rate of 99.25%.We performed an intermediary modeling to examine the mediating roles of nutritional care literacy on the relationship between self-directed learning ability and nursing competence in clinical nurses. RESULTS: Self-directed learning ability was positively correlated with nutritional care  literacy (r=0.792, P<0.001) and nursing competence (r=0.696, P<0.001). Nutritional care literacy was positively correlated with nursing competence (r=0.658, P<0.001). Nutritional care literacy mediated the relationship between self-directed learning ability and nursing competence. The mediating effect accounted for 32.48% of the total effect and 48.10% of the direct effect . CONCLUSIONS: This study confirmed the positive correlation between self-directed learning ability, nutritional care literacy, and nursing competence. Nutritional care  literacy played a mediating role in the relationship between self-directed learning ability and nursing competence. The findings not only provide a novel strategy for cultivating nursing professionals and improving nurse disease care abilities, but also offer a new perspective for nursing educators and managers.