Prevention and management of medical adhesive-related skin injuries in tumor patients with peripheral central venous catheters: a best practice implementation project.

INTRODUCTION: Peripheral central venous catheters are common vascular access devices used in patients with tumors. To prevent catheter shedding and displacement, it is essential to use medical adhesives to secure the catheters. Repeated adhesion and removal of medical adhesives can weaken the barrier function of the skin, leading to medical adhesive-related skin injuries (MARSI), which can increase the patients' pain and medical expenses. OBJECTIVES: The objective of this project was to utilize the best evidence to prevent and manage MARSI in tumor patients with peripheral central venous catheters. METHODS: This evidence-based audit and feedback project was theoretically informed by the JBI Evidence Implementation Framework. The framework involves seven phases in which a project team was established; measurable criteria were selected; baseline data were collected; improvement strategies were implemented to address gaps in compliance; a follow-up audit was conducted to assess improvements in compliance; and sustainability measures were considered. The project also used the JBI Practical Application of Clinical Evidence System (PACES) for project management, including data collection and analysis. The JBI Getting Research into Practice (GRiP) approach was also used to support implementation and compliance. RESULTS: In the baseline audit, the compliance rate for the nine audit criteria was low. In the follow-up audit, the compliance rate significantly improved, with each audit criterion exceeding a minimum of 80%, and four audit criteria reaching 100%. Knowledge of MARSI among nurses and patients significantly improved (p  < 0.05) and the incidence of MARSI among patients with peripheral central venous catheters decreased. CONCLUSIONS: This project successfully enhanced nurses' compliance with MARSI prevention and management and increased the knowledge and skills of both nurses and patients about MARSI. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A285.

Deubiquitination of RIPK2 by OTUB2 augments NOD2 signalling and protective effects in intestinal inflammation.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, but the molecular mechanisms underlying IBD are incompletely understood. In this study, we explored the role and regulating mechanism of otubain 2 (OTUB2), a deubiquitinating enzyme, in IBD. METHODS: To study the function of OTUB2 in IBD, we generated Otub2-/- mice and treated them with dextran sulfate sodium (DSS) to induce experimental colitis. Bone marrow transplantation was performed to identify the cell populations that were affected by OTUB2 in colitis. The molecular mechanism of OTUB2 in signal transduction was studied by various biochemical methods. RESULTS: OTUB2 was highly expressed in colon-infiltrating macrophages in both humans with IBD and mice with DSS-induced experimental colitis. Colitis was significantly aggravated in Otub2-/- mice and bone marrow chimeric mice receiving Otub2-/- bone marrow. OTUB2-deficiency impaired the production of cytokines and chemokines in macrophages in response to the NOD2 agonist muramyl dipeptide (MDP). Upon MDP stimulation, OTUB2 promoted NOD2 signaling by stabilizing RIPK2. Mechanistically, OTUB2 inhibited the proteasomal degradation of RIPK2 by removing K48-linked polyubiquitination on RIPK2, which was mediated by the active C51 residue in OTUB2. In mice, OTUB2 ablation abolished the protective effects of MDP administration in colitis. CONCLUSION: This study identified OTUB2 as a novel regulator of intestinal inflammation.

Circulating tumor DNA in conjunctival melanoma: landscape and surveillance value.

PURPOSE: To evaluate the surveillance value of circulating tumor DNA (ctDNA) for detecting distant metastasis and indicating systemic therapeutic efficacy in conjunctival melanoma (CoM). DESIGN: Retrospective, observational case series. METHODS: From July 2021 to June 2023, 30 CoM patients in our center underwent plasma ctDNA assessment, out of which 12 individuals presented with distant metastases. We employed a 437-gene panel containing common mutations in CoM and common drug-sensitive mutations using next-generation sequencing (NGS) technology to analyze ctDNA mutations in plasma. Clinical and radiological records were used to assess tumor status. The relationship between ctDNA characteristics, tissue gene mutations, and clinical manifestations were explored. RESULTS: CoM-related driver mutations were detected in ctDNA of 11 patients with distant metastasis. The ctDNA were highly consistent with tissue sequencing, mutual driver mutation including BRAF, NRAS, KRAS, NF1, CTNNB1, and TP53 mutation. those with a higher VAF had shorter progression-free survival (PFS, p=0.0475) and overall survival (OS, p=0.0043). The ctDNA variant allele fraction (VAF) was not correlated with the sum of the longest diameters (SLD, p=0.8192) in distant metastasis patients. CONCLUSIONS: Positive plasma ctDNA reflected the presence of metastases. The ctDNA could be used as a complement or alternative to tissue sequencing. High VAF ctDNA might indicate rapid disease progression in distant metastasis patients.

YOD1 sustains NOD2-mediated protective signaling in colitis by stabilizing RIPK2.

Inflammatory bowel disease (IBD) is a disorder causing chronic inflammation in the gastrointestinal tract, and its pathophysiological mechanisms are still under investigation. Here, we find that mice deficient of YOD1, a deubiquitinating enzyme, are highly susceptible to dextran sulfate sodium (DSS)-induced colitis. The bone marrow transplantation experiment reveals that YOD1 derived from hematopoietic cells inhibits DSS colitis. Moreover, YOD1 exerts its protective role by promoting nucleotide-binding oligomerization domain 2 (NOD2)-mediated physiological inflammation in macrophages. Mechanistically, YOD1 inhibits the proteasomal degradation of receptor-interacting serine/threonine kinase 2 (RIPK2) by reducing its K48 polyubiquitination, thereby increasing RIPK2 abundance to enhance NOD2 signaling. Consistently, the protective function of muramyldipeptide, a NOD2 ligand, in experimental colitis is abolished in mice deficient of YOD1. Importantly, YOD1 is upregulated in colon-infiltrating macrophages in patients with colitis. Collectively, this study identifies YOD1 as a novel regulator of colitis.

Novel mutations in acetolactate synthase confer high levels of resistance to tribenuron-methyl in Fagopyrum tataricum.

Tartary buckwheat (Fagopyrum tataricum) field weeds are rich in species, with many weeds causing reduced quality, yield, and crop failure. The selection of herbicide-resistant Tartary buckwheat varieties, while applying low-toxicity and efficient herbicides as a complementary weed control system, is one way to improve Tartary buckwheat yield and quality. Therefore, the development of herbicide-resistant varieties is important for the breeding of Tartary buckwheat. In this experiment, 50 mM ethyl methyl sulfonate solution was used to treat Tartary buckwheat seeds (M1) and then planted in the field. Harvested seeds (M2) were planted in the experiment field of Guizhou University, and when seedlings had 5-7 leaves, the seedlings were sprayed with 166 mg/L tribenuron-methyl (TBM). A total of 15 resistant plants were obtained, of which three were highly resistant. Using the homologous cloning method, an acetolactate synthase (ALS) gene encoding 547 amino acids was identified in Tartary buckwheat. A GTG (valine) to GGA (glycine) mutation (V409G) occurred at position 409 of the ALS gene in the high tribenuron-methyl resistant mutant sm113. The dm36 mutant harbored a double mutation, a deletion mutation at position 405, and a GTG (valine) to GGA (glycine) mutation (V411G) at position 411. The dm110 mutant underwent a double mutation: an ATG (methionine) to AGG (arginine) mutation (M333R) at position 333 and an insertion mutation at position 372. The synthesis of Chl a, Chl b, total Chl, and Car was significantly inhibited by TBM treatment. TBM was more efficient at suppressing the growth of wild-type plants than that of mutant plants. Antioxidant enzyme activities such as ascorbate peroxidase, peroxidase, and superoxide dismutase were significantly higher in resistant plants than in wild-type after spraying with TBM; malondialdehyde content was significantly lower than in wild-type plants after spraying with TBM. Plants with a single-site mutation in the ALS gene could survive, but their growth was affected by herbicide application. In contrast, plants with dual-site mutations in the ALS gene were not affected, indicating that plants with dual-site mutations in the ALS gene showed higher levels of resistance than plants with a single-site mutation in the ALS gene.

Endoscopic detection and diagnostic strategies for minute gastric cancer: A real-world observational study.

BACKGROUND: Minute gastric cancers (MGCs) have a favorable prognosis, but they are too small to be detected by endoscopy, with a maximum diameter ≤ 5 mm. AIM: To explore endoscopic detection and diagnostic strategies for MGCs. METHODS: This was a real-world observational study. The endoscopic and clinicopathological parameters of 191 MGCs between January 2015 and December 2022 were retrospectively analyzed. Endoscopic discoverable opportunity and typical neoplastic features were emphatically reviewed. RESULTS: All MGCs in our study were of a single pathological type, 97.38% (186/191) of which were differentiated-type tumors. White light endoscopy (WLE) detected 84.29% (161/191) of MGCs, and the most common morphology of MGCs found by WLE was protruding. Narrow-band imaging (NBI) secondary observation detected 14.14% (27/191) of MGCs, and the most common morphology of MGCs found by NBI was flat. Another three MGCs were detected by indigo carmine third observation. If a well-demarcated border lesion exhibited a typical neoplastic color, such as yellowish-red or whitish under WLE and brownish under NBI, MGCs should be diagnosed. The proportion with high diagnostic confidence by magnifying endoscopy with NBI (ME-NBI) was significantly higher than the proportion with low diagnostic confidence and the only visible groups (94.19% > 56.92% > 32.50%, P < 0.001). CONCLUSION: WLE combined with NBI and indigo carmine are helpful for detection of MGCs. A clear demarcation line combined with a typical neoplastic color using nonmagnifying observation is sufficient for diagnosis of MGCs. ME-NBI improves the endoscopic diagnostic confidence of MGCs.

Impacts of Environmental Concentrations of Nanoplastics on Zebrafish Neurobehavior and Reproductive Toxicity.

Nanoplastics, as emerging environmental pollutants, can transport contaminants across marine environments, polluting pristine ecosystems and being ingested by marine organisms. This transfer poses a severe threat to global aquatic ecosystems and potentially impacts human health through the food chain. Neurobehavioral and reproductive toxicity are critical areas of concern because they directly affect the survival, health, and population dynamics of aquatic species, which can have cascading effects on the entire ecosystem. Using zebrafish as a model organism, we investigated the toxic effects of environmental concentrations of polystyrene nanoplastics (PS-NPs). Behavioral assessments, including the novel tank test and open field test, demonstrated significant neurobehavioral changes, indicating increased anxiety and depressive behaviors. A pathological analysis of brain and gonadal tissues, along with evaluations of neurobehavioral and reproductive toxicity biomarkers, revealed that exposure to PS-NPs leads to brain tissue lesions, inflammatory responses, oxidative stress activation, hormone level disruptions, and gonadal damage. Real-time quantitative PCR studies of reproductive gene expression further showed that PS-NPs disrupt the endocrine regulation pathways of the brain-pituitary-gonadal (BPG) axis, causing reproductive toxicity with sex-specific differences. These findings provide crucial insights into the impacts of nanoplastics on aquatic organisms and their ecological risks, offering theoretical support for future environmental protection and pollutant management efforts.

Single-cell sequencing depicts tumor architecture and empowers clinical decision in metastatic conjunctival melanoma.

Conjunctival melanoma (CoM) is a potentially devastating tumor that can lead to distant metastasis. Despite various therapeutic strategies for distant metastatic CoM, the clinical outcomes remain unfavorable. Herein, we performed single-cell RNA sequencing (scRNA-seq) of 47,017 cells obtained from normal conjunctival samples (n = 3) and conjunctival melanomas (n = 7). Notably, we noticed a higher abundance of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME), correlated with enhanced angiogenic capacity and increased VEGFR expression in distal metastatic CoM. Additionally, we observed a significant decrease in the proportion of total CD8+ T cells and an increase in the proportion of naive CD8+ T cells, contributing to a relatively quiescent immunological environment in distal metastatic CoM. These findings were confirmed through the analyses of 70,303 single-cell transcriptomes of 7 individual CoM samples, as well as spatially resolved proteomes of an additional 10 samples of CoMs. Due to the increase of VEGFR-mediated angiogenesis and a less active T cell environment in distal metastatic CoMs, a clinical trial (ChiCTR2100045061) has been initiated to evaluate the efficacy of VEGFR blockade in combination with anti-PD1 therapy for patients with distant metastatic CoM, showing promising tumor-inhibitory effects. In conclusion, our study uncovered the landscape and heterogeneity of the TME during CoM tumorigenesis and progression, empowering clinical decisions in the management of distal metastatic CoM. To our knowledge, this is the initial exploration to translate scRNA-seq analysis to a clinical trial dealing with cancer, providing a novel concept by accommodating scRNA-seq data in cancer therapy.

Analyzing the process of achieving common wealth for different groups in China based on the opportunity advantage perspective of income distribution.

Realizing the common wealth of all people is the essential requirement of socialism with Chinese characteristics. Measuring the process of realizing common wealth and the differences between groups is one of the important issues that need to be addressed urgently. In order to reasonably measure the process of realizing common wealth in China, on the premise of horizontal comparability and vertical consistency, the principles of comparability and consistency are introduced, and a comparative method of opportunity advantage based on income distribution is proposed from the perspective of opportunity equity. Using the 2012-2020 CFPS data to measure and test the opportunity advantages and their differences across regions and groups in China. The study found, firstly, that the opportunity advantage persists but tends to diminish across groups, with the more educated group having a more pronounced opportunity advantage, but that this advantage is diminishing over time. Secondly, the doctoral degree group has a greater probability of earning higher incomes, followed by the master's and bachelor's degree groups, but this opportunity advantage, i.e., the probability of earning higher incomes, is diminishing, i.e., the education dividend is diminishing. Third, the difference in opportunity advantage between urban and rural areas still exists, as evidenced by the greater probability of higher incomes in towns than in rural areas, but this advantage has narrowed further over time, with a clear process of urban-rural integration. Fourthly, in terms of gender, men have a certain opportunity advantage over women, but this difference is not significant. Fifthly, in the context of education levels, gender and urban/rural subgroups, under the framework proposed in this paper, China has achieved some success in the process of realizing the common wealth, and is showing a steady upward trend.

The status and influencing factors of abnormal fetal pregnancy outcomes in 265 cases in China: a retrospective study.

Background: With the advancement of prenatal diagnosis technology, the detection rate of fetal abnormalities continues to increase, imposing a significant burden on both society and families. A retrospective analysis of essential information about pregnant women, such as their pregnancy history and delivery details, is crucial for understanding the primary factors that influence pregnancy outcomes in women with fetal abnormalities. This analysis is of great significance for improving the level of pregnancy management and outcomes in pregnant women with fetal abnormalities. Objective: To retrospectively analyze the pregnancy outcomes of women with fetal abnormalities and explore the factors that influence these outcomes. Methods: Pregnant women's pregnancy outcomes were collected from the medical information system and through telephone follow-ups. The chi-square test and logistic regression were used to analyze the factors influencing pregnancy outcomes. Results: Among 265 pregnant women diagnosed with fetal abnormalities, 190 chose to continue the pregnancy, while 75 chose to terminate it. Pregnant women with multiple fetal abnormalities (OR = 3.774, 95% CI [1.640-8.683]) were more likely to choose termination of pregnancy (TOP), and pregnant women who were advised to terminate their pregnancy or make a careful choice were more likely to terminate the pregnancy (OR = 41.113, 95% CI [11.028-153.267]). Conclusion: The number of organs involved in fetal abnormalities and treatment recommendations were identified as the primary factors influencing pregnancy outcomes. Improving awareness of maternal health care during pregnancy, early pregnancy screening technology, and a multidisciplinary diagnosis and treatment approach are of great significance in assisting pregnant women in making informed decisions and improving fetal prognosis.

Electroacupuncture protects the intestinal mucosal barrier in diarrhea-predominant Irritable Bowel Syndrome rats by regulating the MCs/Tryptase/PAR-2/MLCK pathway.

OBJECTIVE: The pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D) is related to damage to the intestinal mucosal barrier function. Based on the Mast cell (MC)/Tryptase/Protease-activated receptor-2 (PAR-2)/Myosin light chain kinase (MLCK) pathway, this study explored the effect of electroacupuncture (EA) on IBS-D rats and its possible mechanism of protecting the intestinal mucosal barrier. METHODS: The IBS-D rat model was established by mother-offspring separation, acetic acid enema, and chronic restraint stress. The efficacy of EA on IBS-D rats was evaluated by observing the rate of loose stool (LSP) and the minimum volume threshold of abdominal withdrawal reflex (AWR) in rats. Mast cells and the ultrastructure of intestinal mucosa were observed by H&E staining, toluidine blue staining, and transmission electron microscopy. The expression levels of Tryptase, PAR-2, MLCK, zonula occludens-1 (ZO-1), and Occludin in rats were detected by ELISA, qRT-PCR, and western blot. RESULTS: After 7 days of intervention, compared to the IBS-D group, the loose stool rates of rats in IBS-D + EA group and IBS-D + ketotifen group were decreased (P < 0.01), the minimum volume thresholds of AWR were improved (P < 0.01), the inflammation of colon tissue decreased, the number of MCs were decreased (P < 0.01), the expression of Tryptase, PAR-2, and MLCK were lowered (P < 0.01, P < 0.05), and the expression of ZO-1 and Occludin were enhanced (P < 0.01, P < 0.05). Compared to the EA group, there was no significant difference in each index between the ketotifen groups (P > 0.05). CONCLUSION: EA has a good therapeutic effect on IBS-D rats. Regulating the MCs/Tryptase/PAR-2/MLCK pathway may be a mechanism to protect the intestinal mucosal barrier.

Incidence and risk factors of neonatal hypothermia: A systematic review and meta-analysis.

AIM: Hypothermia poses a threat to the health and lives of newborns. Therefore, it is essential to identify the factors that influence neonatal hypothermia and provide targeted intervention suggestions for clinical practice to reduce its occurrence. METHODS: We conducted a literature search to identify factors influencing neonatal hypothermia and performed a meta-analysis to determine the prevalence of neonatal hypothermia and its associated factors. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of cohort and case-control studies, while the Agency for Healthcare Research and Quality (AHRQ) was used to evaluate the quality of cross-sectional studies. RESULTS: Eighteen studies involving 44 532 newborns from 13 countries were included. The incidence of neonatal hypothermia was 52.5% (95% CI: 0.37, 0.68). Factors such as no skin-to-skin contact, prematurity, low birth weight, delayed breastfeeding, asphyxiation and resuscitation after birth, low APGAR score, not wearing a cap, and caesarean section were found to affect neonatal hypothermia. CONCLUSION: Multiple factors influence neonatal hypothermia, and clinicians can utilise these factors to develop targeted intervention measures to prevent and reduce the incidence of neonatal hypothermia.

Engineered Cell Membrane-Coated Nanoparticles: New Strategies in Glioma Targeted Therapy and Immune Modulation.

Gliomas, the most prevalent primary brain tumors, pose considerable challenges due to their heterogeneity, intricate tumor microenvironment (TME), and blood-brain barrier (BBB), which restrict the effectiveness of traditional treatments like surgery and chemotherapy. This review provides an overview of engineered cell membrane technologies in glioma therapy, with a specific emphasis on targeted drug delivery and modulation of the immune microenvironment. This study investigates the progress in engineered cell membranes, encompassing physical, chemical, and genetic alterations, to improve drug delivery across the BBB and effectively target gliomas. The examination focuses on the interaction of engineered cell membrane-coated nanoparticles (ECM-NPs) with the TME in gliomas, emphasizing their potential to modulate glioma cell behavior and TME to enhance therapeutic efficacy. The review further explores the involvement of ECM-NPs in immunomodulation techniques, highlighting their impact on immune reactions. While facing obstacles related to membrane stability and manufacturing scalability, the review outlines forthcoming research directions focused on enhancing membrane performance. This review underscores the promise of ECM-NPs in surpassing conventional therapeutic constraints, proposing novel approaches for efficacious glioma treatment.

Behavioral Studies of Zebrafish Reveal a New Perspective on the Reproductive Toxicity of Micro- and Nanoplastics.

The escalating prevalence of microplastics and nanoplastics in aquatic environments is a major challenge affecting the behavior and reproductive health of aquatic organisms while posing potential risks to human health and ecosystems. This review focuses on the neurobehavioral changes and reproductive toxicity of MNPs in zebrafish and their relationships. At the same time, the neurobehavioral changes caused by MNPs were studied, and the synergistic effects of the interaction of these pollutants with other environmental contaminants were explored. In addition, zebrafish, as a model organism, provide valuable insights into the subtle but important effects of MNPs on reproductive behavior, which is critical for understanding reproductive success, suggesting that behavioral changes can serve as an early biomarker of reproductive toxicity. In addition, based on classical endocrine disruptor models and behavioral research methods, the current status of the research on the reproductive toxicity of MNPs in zebrafish was reviewed, which further indicated that the behavioral parameters of zebrafish can be used as an effective and rapid tool to evaluate the reproductive toxicity of MNPs. However, behavioral methods for rapidly assessing the toxicity of MNPs are still an area of exploration. To address limitations and challenges in the current scope of research, this review outlines future research directions with the aim of improving our understanding of the environmental and health impacts of MNPs. This work aims to inform targeted environmental policies and advance public health strategies to address the growing challenge of MNPs pollution.

The role of the annexin A protein family at the maternal-fetal interface.

Successful pregnancy requires the tolerance of the maternal immune system for the semi-allogeneic embryo, as well as a synchrony between the receptive endometrium and the competent embryo. The annexin family belongs to calcium-regulated phospholipid-binding protein, which functions as a membrane skeleton to stabilize the lipid bilayer and participate in various biological processes in humans. There is an abundance of the annexin family at the maternal-fetal interface, and it exerts a crucial role in embryo implantation and the subsequent development of the placenta. Altered expression of the annexin family and dysfunction of annexin proteins or polymorphisms of the ANXA gene are involved in a range of pregnancy complications. In this review, we summarize the current knowledge of the annexin A protein family at the maternal-fetal interface and its association with female reproductive disorders, suggesting the use of ANXA as the potential therapeutic target in the clinical diagnosis and treatment of pregnancy complications.

"Machine replacement" or "job creation": How does artificial intelligence impact employment patterns in China's manufacturing industry?

Artificial intelligence (AI), as an important engine for promoting high-quality economic development, should not be overlooked in terms of its impact on the employment of the labor force while promoting the digital and intelligent transformation of industries. In the face of the complex international environment and non-systemic shocks, it is of great significance to explore whether it is "machine replacement" or "job creation" in the process of the integration of AI and industry, as well as the impact of technological progress on the employment pattern of the labor force, in order to promote the economic development, respond to and solve the employment problem. It is of great significance to promote economic development and cope with and solve the employment problem. Based on the task model, this paper analyses the mechanism of the impact of AI on the employment pattern of manufacturing industry. Meanwhile, based on the provincial panel data of China's manufacturing industry from 2011 to 2020, it empirically examines the impact of AI on the total employment, employment structure and employment quality of the labor force, and analyses the multiple responses of AI on the employment pattern of the manufacturing industry. The study shows that: Firstly, the level of development of AI and the total amount of employment is a positive U-shaped relationship, the short term is dominated by the substitution effect, and the long term is dominated by the creation effect; Secondly, with regard to the employment structure, low-skilled labor is more likely to be replaced. The financial, accommodation and catering industries are relatively less affected by the spillover effects of the manufacturing industry; Third, with regard to the employment quality, the gap between urban and rural incomes has eased, with per capita net income of rural residents rising to a higher degree than per capita disposable income of urban residents. Thus, in order to further address the impact of AI on the employment patterns of the labor force, the level of AI development should be increased while expanding employment channels, paying attention to labor force skills training, reinforcing the leading role of developed regions, and accelerating regional integration and urban-rural integration, so as to share the dividends of technological progress.

Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.

Telomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high expression is associated with poor prognosis. Flavokavain B derivative FKB04 potently inhibited TRF2 expression in liver cancer cells while having limited effects on the other five shelterin subunits. Moreover, FKB04 treatment induced telomere shortening and increased the amounts of telomere-free ends, leading to the destruction of T-loop structure. Consequently, FKB04 promoted liver cancer cell senescence without modulating apoptosis levels. In corroboration with these findings, FKB04 inhibited tumor cell growth by promoting telomeric TRF2 deficiency-induced telomere shortening in a mouse xenograft tumor model, with no obvious side effects. These results demonstrate that TRF2 is a potential therapeutic target for liver cancer and suggest that FKB04 may be a selective small-molecule inhibitor of TRF2, showing promise in the treatment of liver cancer.

Genetic landscape and prognosis of conjunctival melanoma in Chinese patients.

AIMS: Conjunctival melanoma (CoM) is a rare but highly lethal ocular melanoma and there is limited understanding of its genetic background. To update the genetic landscape of CoM, whole-exome sequencing (WES) and targeted next-generation sequencing (NGS) were performed. METHODS: Among 30 patients who were diagnosed and treated at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from January 2018 to January 2023, WES was performed on 16 patients, while targeted NGS was conducted on 14 patients. Samples were analysed to identify the mutated genes, and the potential predictive factors for progression-free survival were evaluated. Furthermore, the expression of the mutated gene was detected and validated in a 30-patient cohort by immunofluorescence. RESULTS: Mutations were verified in classic genes, such as BRAF (n=9), NRAS (n=5) and NF1 (n=6). Mutated FAT4 and BRAF were associated with an increased risk for the progression of CoM. Moreover, decreased expression of FAT4 was detected in CoM patients with a worse prognosis. CONCLUSIONS: The molecular landscape of CoM in Chinese patients was updated with new findings. A relatively high frequency of mutated FAT4 was determined in Chinese CoM patients, and decreased expression of FAT4 was found in patients with worse prognoses. In addition, both BRAF mutations and FAT4 mutations could serve as predictive factors for CoM patients.

The invisible Threat: Assessing the reproductive and transgenerational impacts of micro- and nanoplastics on fish.

Micro- and nanoplastics (MNPs), emerging as pervasive environmental pollutants, present multifaceted threats to diverse ecosystems. This review critically examines the ability of MNPs to traverse biological barriers in fish, leading to their accumulation in gonadal tissues and subsequent reproductive toxicity. A focal concern is the potential transgenerational harm, where offspring not directly exposed to MNPs exhibit toxic effects. Characterized by extensive specific surface areas and marked surface hydrophobicity, MNPs readily adsorb and concentrate other environmental contaminants, potentially intensifying reproductive and transgenerational toxicity. This comprehensive analysis aims to provide profound insights into the repercussions of MNPs on fish reproductive health and progeny, highlighting the intricate interplay between MNPs and other pollutants. We delve into the mechanisms of MNPs-induced reproductive toxicity, including gonadal histopathologic alterations, oxidative stress, and disruptions in the hypothalamic-pituitary-gonadal axis. The review also underscores the urgency for future research to explore the size-specific toxic dynamics of MNPs and the long-term implications of chronic exposure. Understanding these aspects is crucial for assessing the ecological risks posed by MNPs and formulating strategies to safeguard aquatic life.