Mechanism of norcantharidin intervention in gastric cancer: analysis based on antitumor proprietary Chinese medicine database, network pharmacology, and transcriptomics.

BACKGROUND: Combining antitumor proprietary Chinese medicine (pCm) with radiotherapy and chemotherapy can effectively improve tumor cure rates and enhance patients' quality of life. Gastric cancer (GC) severely endangers public health. Despite satisfactory therapeutic effects achieved by using antitumor pCm to treat GC, its underlying mechanism remains unclear. OBJECTIVE: To integrate existing research data, construct a database of antitumor pCm, and study the intervention mechanisms in GC by focusing on their monomer components. METHODS: We constructed an antitumor pCm database based on China's medical insurance catalog, and employed network pharmacology, molecular docking methods, cell experiments, transcriptomics, and bioinformatics to investigate the intervention mechanisms of effective pCm components for GC. RESULTS: The study built an antitumor pCm database including 55 pCms, 171 Chinese herbal medicines, 1955 chemical components, 2104 targets, and 32 disease information. Network pharmacology and molecular docking technology identified norcantharidin as an effective component of antitumor pCm. In vitro experiments showed that norcantharidin effectively inhibited GC cell proliferation, migration, and invasion; blocked the G2/M cell cycle phase; and induced GC cell apoptosis. Transcriptomic results revealed that norcantharidin affected biological processes, such as cell adhesion, migration, and inflammatory responses by influencing PI3K-AKT, NF-κB, JAK-STAT, TNF-α signaling pathways, and EMT-related pathways. Core molecules of norcantharidin involved in GC intervention include SERPINE1, SHOX2, SOX4, PRDM1, TGFR3, TOX, PAX9, IL2RB, LAG3, and IL15RA. Additionally, the key target SERPINE1 was identified using bioinformatics methods. CONCLUSION: Norcantharidin, as an effective component of anti-tumor pCm, exerts its therapeutic effects on GC by influencing biological processes such as cell adhesion, migration, and inflammation. This study provides a foundation and research strategy for the post-marketing re-evaluation of antitumor pCms.

mer-M(CO)3(PNP)0/+ pincer complexes (M = W(0) or Re(I); PNP = 4,5-bis(diphenylphosphino)acridine): synthesis, spectroscopy and anti-Kasha emission.

Two isoelectronic and isostructural W(0) and Re(I) complexes mer-W(CO)3(PNP) (1) and [mer-Re(CO)3(PNP)]Cl (2) (PNP = 4,5-bis(diphenylphosphino)acridine) were synthesized and characterized by X-ray diffraction, infrared, electronic absorption and emission spectroscopy, and cyclic voltammetry. Structures of these complexes show a metal center bonded to the pincer ligand and two axial CO and one equatorial CO ligands. DFT calculations showed that the LUMOs of both complexes are the lowest energy π* orbitals localized in the acridine part of the ligand. The HOMO of 1 is dominated by the dπ orbital of W(0) while the HOMO of 2 has a substantial contribution from the highest energy π orbital of the acridine ring. TD-DFT calculations were performed to assist assignment of the UV-vis absorption spectra. The UV-vis absorption spectrum of 1 shows a very low energy W → π* (acridine) metal-to-ligand-charge-transfer (MLCT) absorption band that ranges from visible (500 nm) to near-infrared (>900 nm) regions and an intense acridine π → π* absorption band at 410 nm. There is a blue-green window in the ∼450-500 nm range between the π → π* and W → π*(acridine) MLCT absorptions. The absorption spectrum of 2, dominated by intense π → π* absorptions, shows no distinct low energy MLCT band. Complex 1 is luminescent, displaying acridine-based ππ* fluorescence at 501 nm which is anti-Kasha as it is higher in energy than the lowest energy excited state.

Epstein-Barr Viruses: Their Immune Evasion Strategies and Implications for Autoimmune Diseases.

Epstein-Barr virus (EBV), a member of the γ-herpesvirus family, is one of the most prevalent and persistent human viruses, infecting up to 90% of the adult population globally. EBV's life cycle includes primary infection, latency, and lytic reactivation, with the virus primarily infecting B cells and epithelial cells. This virus has evolved sophisticated strategies to evade both innate and adaptive immune responses, thereby maintaining a lifelong presence within the host. This persistence is facilitated by the expression of latent genes such as EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), which play crucial roles in viral latency and oncogenesis. In addition to their well-known roles in several types of cancer, including nasopharyngeal carcinoma and B-cell lymphomas, recent studies have identified the pathogenic roles of EBV in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. This review highlights the intricate interactions between EBV and the host immune system, underscoring the need for further research to develop effective therapeutic and preventive strategies against EBV-associated diseases.

mmWave-RM: A Respiration Monitoring and Pattern Classification System Based on mmWave Radar.

Breathing is one of the body's most basic functions and abnormal breathing can indicate underlying cardiopulmonary problems. Monitoring respiratory abnormalities can help with early detection and reduce the risk of cardiopulmonary diseases. In this study, a 77 GHz frequency-modulated continuous wave (FMCW) millimetre-wave (mmWave) radar was used to detect different types of respiratory signals from the human body in a non-contact manner for respiratory monitoring (RM). To solve the problem of noise interference in the daily environment on the recognition of different breathing patterns, the system utilised breathing signals captured by the millimetre-wave radar. Firstly, we filtered out most of the static noise using a signal superposition method and designed an elliptical filter to obtain a more accurate image of the breathing waveforms between 0.1 Hz and 0.5 Hz. Secondly, combined with the histogram of oriented gradient (HOG) feature extraction algorithm, K-nearest neighbours (KNN), convolutional neural network (CNN), and HOG support vector machine (G-SVM) were used to classify four breathing modes, namely, normal breathing, slow and deep breathing, quick breathing, and meningitic breathing. The overall accuracy reached up to 94.75%. Therefore, this study effectively supports daily medical monitoring.

The combination of detection and simulation for the distribution and sourcing of microplastics in Shing Mun River estuary, Hong Kong.

For the first time, combined detection and simulation was performed on microplastic (MP) debris in surface water, sediment, and oyster samples at ten coastal sites of Shing Mun River estuary, Hong Kong at different tidal conditions. The MP debris were extracted and detected using Fourier transform infrared (FT-IR) spectroscopy, and the simulation was conducted using Weather Research & Forecasting Model (WRF) / Regional Ocean Modelling System (ROMS) coupled hydro-dynamic modelling and the subsequent Lagrangian particle tracking. The results demonstrated the majority of polyethylene (with partial chlorine substitution) debris among all the MPs found, and great spatial and tidal variabilities of MP concentrations were observed. The combination of MP observation and simulations referred to the interpretation that a considerable percentage of MPs found in this study originated from South China Sea. Those MPs were probably transported to Tolo Harbour through sea currents and drifted inshore and offshore with tides. This study provided baseline measures of MP concentrations in Shing Mun River estuary and comprehensive understanding for how MPs transport and distribute within a dynamic estuarine system.

Ultrathin and Self-Supporting MOF/COF-Based Composite Membranes for Hydrogen Separation and Purification from Coke Oven Gas.

Coke oven gas (COG) is considered to be one of the most likely raw materials for large-scale H2 production in the near or medium term, with membrane separation technologies standing out from traditional technologies due to their less energy-intensive structures as well as simple operation and occupation. Based on the "MOF-in/on-COF" pore modification strategy, the COF membrane (named the PBD membrane) and ZIF-67 were used as assembly elements to design advanced molecular sieving membranes for hydrogen separation. The composition and microstructure of membranes before and after ZIF-67 loading as well as ZIF-67-in-PBD membranes under different preparation conditions (metal ion concentration, metal-ligand ratio, and reaction time) were investigated by various characterizations to reveal the synthesis regularity and microstructure regulation. Furthermore, H2/CH4 separation performances and separation mechanisms were also analyzed and compared. Finally, a dense, continuous, ultrathin, and self-supporting ZIF-67-in-PBD membrane with a Co2+ concentration of 0.02 mol/L, a metal-ligand ratio of 1:4, and a reaction time of 6 h exhibited the largest specific surface area, micropore proportion, and the best H2/CH4 separation selectivity (α = 33.48), which was significantly higher than the Robeson upper limit and was in a leading position among reported MOF membranes. The separation mechanism was mainly size screening, and adsorption selectivity also contributed a little.

4-Octyl itaconate alleviates dextran sulfate sodium-induced ulcerative colitis in mice via activating the KEAP1-NRF2 pathway.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease with a relapsing-remitting course. Although its etiology remains unknown, excessive oxidative stress in colon is a major intermediate factor that can promote the progression of UC. In the present study, we investigated the effect and the underlying mechanisms of 4-Octyl itaconate (OI) on dextran sulfate sodium (DSS)-induced UC in mice. Our work identified that OI alleviated the colitis by reducing the oxidative stress and the apoptosis in colon tissue, then increasing the tight junction proteins expression and in turn enhancing the intestinal barrier function, thereby creating less severe inflammatory responses. Moreover, our results demonstrated that OI reduced the Kelch-like ECH-associated protein 1 (KEAP1) expression and subsequent upregulated nuclear factor E2-related factor (NRF2) expression and its nuclear translocation which in turn induced the expression of glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase 1 (NQO1). In addition, ML385, a NRF2 antagonist, can inhibit the protective effects of OI on UC, indicating that the role of OI in this colitis model could be dependent on the activation of KEAP1-NRF2 pathway. Notably, OI co-administration significantly enhanced the therapeutic effects of mesalazine or 1400W on UC. Collectively, itaconate may have a great potential for use in the treatment of IBD.

Investigation on the efficiency of lentinan for injection combining cisplatin on treating malignant pleural effusion based on systematic review and meta-analysis.

BACKGROUND: Malignant pleural effusion (MPE) is a frequently observed complication in advanced malignant tumors. Clinical studies have shown that lentinan for injection (LNT) is beneficial for improving patients' quality of life and prolonging their survival. The purpose of this meta-analysis is to evaluate the efficacy and safety of LNT combining cisplatin in the treatment of MPE. METHODS: Randomized controlled trials (RCTs) of LNT combining cisplatin in the treatment of MPE were searched in 6 literature databases from the establishment time of each database by 2 researchers. According to the inclusion criteria, 2 researchers independently screened studies, assessed the risk of bias and conducted subgroup analyses for different outcome indicators according to the specific characteristics of the included literature. Analyzing the data by Revman software, and evaluating the stability of the results by Stata software. RESULTS: A total of 52 RCTs were included. The results showed that combined use of LNT and cisplatin could improve the treatment effect, and the difference between groups was statistically significant (RR = 1.40, 95%CI: 1.33 ~ 1.46, P < .001). And the combined use of LNT could increase the quality of life (RR = 1.45, 95%CI: 1.35 ~ 1.56, P < .001). The using of LNT could significantly decrease the incidence of gastrointestinal reactions (RR = 0.86, 95%CI: 0.78 ~ 0.94, P < .001). Sensitivity analysis results showed that there were no qualitative changes in the indicator, and suggested the possibility of publication bias. CONCLUSIONS: Available evidence suggested the combined use of LNT and cisplatin showed better efficacy in treating MPE without increasing ADR incidence than using cisplatin alone. LNT is an ideal treatment for MPE, which has high clinical application value.

Global quantification of emerging and legacy per- and polyfluoroalkyl substances in indoor dust: Levels, profiles and human exposure.

This study investigated the occurrence and distribution of per- and polyfluoroalkyl substances (PFASs) in house dust samples from six regions across four continents. PFASs were detected in all indoor dust samples, with total median concentrations ranging from 17.3 to 197 ng/g. Among the thirty-one PFAS analytes, eight compounds, including emerging PFASs, exhibited high detection frequencies in house dust from all six locations. The levels of PFASs varied by region, with higher concentrations found in Adelaide (Australia), Tianjin (China), and Carbondale (United States, U.S.). Moreover, PFAS composition profiles also differed among regions. Dust from Australia and the U.S. contained high levels of 6:2 fluorotelomer phosphate ester (6:2 diPAP), while perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were predominant in other regions. Furthermore, our results indicate that socioeconomic factors impact PFAS levels. The assessment of human exposure through dust ingestion and dermal contact indicates that toddlers may experience higher exposure levels than adults. However, the hazard quotients of PFASs for both toddlers and adults were below one, indicating significant health risks are unlikely. Our study highlights the widespread occurrence of PFASs in global indoor dust and the need for continued monitoring and regulation of these chemicals.

Molecular insights into gastric cancer: The impact of TGFBR2 and hsa-mir-107 revealed by microarray sequencing and bioinformatics.

BACKGROUND: Gastric carcinoma (GC) remains a significant therapeutic challenge, garnering widespread attention. Oxymatrine (OMT), an active component of the traditional Chinese medicine compound Kushen injection (CKI), has shown promising results in combination with chemotherapy for the treatment of GC. However, the molecular mechanisms underlying OMT's therapeutic effects in GC have yet to be elucidated. METHODS: The transcriptomic expression data of HGC-27 post-OMT intervention were obtained through microarray sequencing, while the miRNA and mRNA sequencing data for GC patients were sourced from the TCGA database. The mechanism of OMT intervention in GC is analyzed in multiple aspects, including Protein-Protein Interactions (PPI), Competitive Endogenous RNA (ceRNA) networks, correlation and co-expression analyses, immune infiltration, and clinical implications. RESULTS: By analyzing key modules, five critical mRNAs were identified, and their interacting miRNAs were predicted to construct a ceRNA network. Among these, TGFBR2 and hsa-miR-107 have correlations or co-expression relationships with other genes in the network. They are differentially expressed in most other cancers, associated with prognosis, and have diagnostic value. TGFBR2 also exhibits immune infiltration phenomena, and its high expression is linked to poor patient prognosis. Low expression of hsa-miR-107 is associated with poor patient prognosis. OMT may act on the TGFß/Smad signaling pathway or negatively regulate the WNT signaling pathway through the hsa-miR-107/BTRC axis, thereby inhibiting the onset and progression of GC. CONCLUSION: The mechanisms of OMT intervention in GC are diverse, TGFBR2 and hsa-miR-107 may serve as prognostic molecular biomarkers or potential therapeutic targets.

Focused ultrasound-mediated cerium-based nanoreactor against Parkinson's disease via ROS regulation and microglia polarization.

Neuronal damage caused by oxidative stress and inflammatory microenvironment dominated by microglia are the main obstacles in the treatment of Parkinson's disease (PD). In this study, we developed an integrated nanoreactor Q@CeBG by encapsulating CeO2 nanozyme and quercetin (Que) into glutathione-modified bovine serum albumin, and then selected focused ultrasound (FUS) to temporarily open the blood-brain barrier (BBB) to enhance the accumulation level of Q@CeBG in the brain. Q@CeBG exhibited superior multi-ROS scavenging activity. Under the assistance of FUS, Q@CeBG nanoreactor can penetrate the BBB and act on neurons as well as microglia, reducing the neuron's oxidative stress level and polarizing microglia's phenotype from proinflammatory M1 to anti-inflammatory M2. In vitro and In vivo experiments demonstrated that Q@CeBG nanoreactor with good biocompatibility exhibit outstanding neuroprotection and immunomodulatory effects. In short, this dual synergetic nanoreactor will become a reliable platform against PD.

Exploring the mechanism of action of Shuangyang houbitong granules in the treatment of acute pharyngitis based on network pharmacology and molecular docking.

BACKGROUND: Acute pharyngitis (AP) refers to the acute inflammation of the pharynx, characterized by swelling and pain in the throat. Shuangyang houbitong granules (SHG), a traditional Chinese medicine compound, have been found to be effective in providing relief from symptoms associated with AP. METHODS: The chemical components of SHG were screened using Traditional Chinese Medicine Systems Pharmacology database, HERB database, and China National Knowledge Infrastructure. The targets of the granules were predicted using SwissTargetPrediction database. A network was constructed based on the targets of AP obtained from Genecards database, and protein-protein interaction analysis was performed on the intersection targets using STRING database. Key targets were screened for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and the binding activity of components and targets was predicted using AutoDockTools-1.5.7. RESULTS: A total of 65 components of SHG that met the screening criteria were retrieved, resulting in 867 corresponding targets. Additionally, 1086 AP target genes were retrieved, and 272 gene targets were obtained from the intersection as potential targets for SHG in the treatment of AP. Molecular docking results showed that the core components genkwanin, acacetin, apigenin, quercetin can stably bind to the core targets glyceraldehyde 3-phosphate dehydrogenase, interleukin 6, tumor necrosis factor, serine/threonine protein kinase, tumor protein 53, and epidermal growth factor receptor. CONCLUSION: The research results preliminarily predict and verify the mechanism of action of SHG in the treatment of AP, providing insights for further in-depth research.

Airborne Nanoplastics Exposure Inducing Irreversible Glucose Increase and Complete Hepatic Insulin Resistance.

As an emerging type of pollutant, microplastics have become a global environmental problem. Approximately, a fifth of the global burden of type 2 diabetes can be attributed to air particulate pollution. However, scientific knowledge remains limited about the effects of airborne nanoplastics (NPs) exposure on metabolic diseases. In this experiment, a whole-body exposure system was used to simulate the real atmospheric environment, and three exposure concentrations combined with the actual environmental concentration were selected to explore the effects of airborne NPs on metabolic diseases. Based on histological analyses, metabolic studies, gene expression, metabolites, and molecular signaling analyses, mice exposed to airborne NPs were observed to show a phenotype of systemic inflammation and complete insulin resistance featuring excessive drinking and eating, weight loss, elevated blood glucose, and decreased triglyceride levels. After airborne NPs exposure, mice were intolerant to glucose and tolerant to insulin. In addition, airborne NPs exposure could result in long-term irreversible hyperglycemia. Together, the research findings provide a strong basis for understanding the hazards of airborne nanopollution on metabolic disorders.

Improving flame retardant and electromagnetic interference shielding properties of poly(lactic acid)/poly(ε-caprolactone) composites using catalytic imidazolium modified CNTs and ammonium polyphosphate.

The flame retardants and electromagnetic interference (EMI) shielding performance were enhanced by using imidazolium-functionalized polyurethane (IPU) modified multi-walled carbon nanotubes (CNTs) and ammonium polyphosphate (APP) for polylactic acid (PLA)/polycaprolactone (PCL) composites. The PLA/PCL/10APP/8CNT/1.6IPU composite containing 10 wt% APP and 8 wt% imidazolium modified CNTs reached the limiting oxygen index (LOI) value of 30.3 % and passed the V-0 rating in UL-94 tests. Moreover, the peak of the heat release rate (pHRR) and total heat release (THR) for this composite reached around 302 kW/m2 and 64 KJ/m2, which were decreased by 39.1 % and 15.8 % compared with that of PLA/PCL/10APP composite. The improved flame retardancy was attributed to the interplay of catalytic, barrier, and condensed char forming of imidazolium-modified CNTs and APP. IPU catalyzed the charring effect of the polymer matrix during combustion and regulated the migration of more CNTs to disperse at the two-phase interface. The dispersion of imidazolium-modified CNTs and co-continuous phase structure of the composites can establish continuous conductive pathways. The PLA/PCL/APP/CNT/IPU composite obtained a higher conductivity compared to the PLA/PCL/APP/CNT composite and whose EMI SE reached 33.9 dB, which is a promising candidate for next-generation sustainable and protective plastics.

Systematic review and meta-analysis on the efficacy and safety of Injectable Lentinan combined with chemotherapy in the treatment of gastric cancer.

BACKGROUND: This study employed a meta-analysis to evaluate the efficacy and safety of adjunctive treatment with injectable Lentinan (LNT) in combination with chemotherapy for gastric cancer (GC). METHODS: Computer-based searches of 6 databases were performed to identify randomized controlled trials (RCTs) relevant to the treatment of GC with LNT through mid-March 2023. Two independent researchers performed risk of bias assessment and trial sequential analysis(TSA), extracted the data and used Revman 5.3 software for data analysis. The certainty of evidence was graded based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS: A total of 31 RCTs with 2729 patients were included in the analysis. The results revealed that adjunctive therapy with LNT was associated with improved treatment efficacy (RR = 1.48, 95%CI: 1.36 ∼ 1.61, p < 0.00001), improvement in clusters of differentiation (CD3+, CD4+, and CD4+/CD8+), natural killer (NK) cells, and quality of life assessment (RR = 1.32, 95%CI: 1.20 ∼ 1.45, p < 0.00001) compared to using chemotherapy alone. In addition, there was a reduction in CD8+ levels, incidence of white blood cell decline, gastrointestinal reactions, and platelet decline. TSA results indicated that there was sufficient evidence to draw firm conclusions about these outcomes, and the GRADE scores showed 'high' or 'moderate' quality of evidence for these outcomes. CONCLUSION: The efficacy of treatment of GC with LNT in combination with chemotherapy was found to be better than chemotherapy alone. And no serious adverse effects were observed. However, further RCTs are needed to further validate the results of this study.

D-Mannose promotes recovery from experimental colitis by inducing AMPK phosphorylation to stimulate epithelial repair.

Delayed mucosal healing and impaired intestinal epithelial barrier function have been implicated in the pathogenesis of ulcerative colitis (UC). Accordingly, restoration of epithelial barrier function as a means to reshape mucosal homeostasis represents an important strategy for use in the treatment of UC. In this study, we examined the role and mechanisms of D-mannose in the recovery of colitis as assessed in both animal and cell models. We found that D-mannose ameliorated inflammation, promoted mucosal healing in the colon and therefore was able to induce the recovery of UC. Furthermore, D-mannose increased the expression of tight junction (TJ) proteins and reduced the intestinal permeability during the recovery of colitis. Moreover, D-mannose inhibited M1 macrophage polarization and promoted M2 macrophage polarization via inducing AMPK phosphorylation while reducing mTOR phosphorylation in both models. In addition, increased TJ protein expression and decreased paracellular permeability were observed in NCM460 cells when incubated with the supernatants of D-mannose-treated RAW264.7 cells, suggesting that M1/M2 polarization induced by D-mannose modulates the expression of TJ proteins. Further study showed that D-mannose significantly upregulated the expression of TJ proteins in DSS-treated NCM460 cells by inducing AMPK phosphorylation, indicating a direct protective effect on epithelial cells. Finally, the protective effects of D-mannose were significantly abrogated by the presence of compound C, an AMPK inhibitor. Taken together, our data indicate that D-mannose can alleviate inflammation and foster epithelial restitution in UC recovery by inducing the TJ protein expression, which are achieved by inducing AMPK phosphorylation in the epithelium and/or macrophages.

A new strategy to identify ADAM12 and PDGFRB as a novel prognostic biomarker for matrine regulates gastric cancer via high throughput chip mining and computational verification.

BACKGROUND: Gastric cancer is a life-threatening disease that poses a serious risk to human health. Although there are numerous molecular targets for gastric cancer in clinical practice, they often exhibit low specificity and sensitivity. Consequently, this can result in a low early diagnosis rate, delayed treatment, and poor prognosis for patients with gastric cancer. Hence, it remains crucial to identify more precise diagnostic markers for this disease. METHODS: This study utilized ceRNA chips and bioinformatics methods to investigate the key genes and mechanisms involved in matrine intervention in gastric cancer cells. RESULTS: ADAM12 and PDGFRB are the key genes that are down-regulated after matrine intervention in gastric cancer cells. By conducting bioinformatics analysis, two ceRNA regulatory axes were identified, which are associated with the prognosis of gastric cancer. These axes are lncRNA DGCR5/hsa-miR-206/ADAM12 and circRNA ITGA3/hsa-miR-24-3p/PDGFRB. CONCLUSION: The low expression of ADAM12 may weaken the digestion of extracellular matrix (ECM) molecules, which can result in the invasion and metastasis of tumor cells. This occurs without the catalysis of ECM proteases, thereby impacting the invasion and metastasis of gastric cancer cells. Additionally, the analysis of immune infiltration suggests that ADAM12 and PDGFRB may influence changes in the tumor immune microenvironment, thereby affecting the occurrence and development of gastric cancer. This study contributes to a deeper understanding of the role of the matrine-related ceRNA network in gastric cancer, providing a reference for clinical diagnosis and treatment. It holds significant importance in discovering new drug treatment targets.

Toxic effects and mechanisms of nanoplastics on embryonic brain development using brain organoids model.

Nanoplastics can be easily absorbed into the human body through inhalation, ingestion, and skin contact due to their physicochemical property. Despite the numerous studies postulating the potential adverse effects of environmental exposure to nanoplastics on neurodevelopment, the effects of nanoplastics and their regulatory mechanisms have not been specifically elucidated. We focused on the toxic effects of nanoplastics on brain developmental processes by investigating their interactions with brain organoids. Our findings indicated that nanoplastics exposure caused cellular dysfunction and structural disorders. Nanoplastics adversely affected critical cells in brain organoids, resulting in the reduction of neural precursor cells and neuronal cells. The expression of neural cadherin was also inhibited, which might lead to impaired axonal extension and formation of synaptic connections. In addition, transcriptome sequencing was performed to study the effects of different concentrations of nanoplastics on the signaling pathway. The qRT-PCR analysis confirmed that nanoplastics exposure resulted in decreased expression of several genes related to the Wnt signaling pathway, suggesting that nanoplastics may adversely affect embryonic brain growth through the suppression of the expression of these genes. Our research findings shed light on the deleterious effects of nanoplastics on embryonic brain development and have significant implications for the field of environmental toxicology.

Crosstalk between Platelets and SARS-CoV-2: Implications in Thrombo-Inflammatory Complications in COVID-19.

The SARS-CoV-2 virus, causing the devastating COVID-19 pandemic, has been reported to affect platelets and cause increased thrombotic events, hinting at the possible bidirectional interactions between platelets and the virus. In this review, we discuss the potential mechanisms underlying the increased thrombotic events as well as altered platelet count and activity in COVID-19. Inspired by existing knowledge on platelet-pathogen interactions, we propose several potential antiviral strategies that platelets might undertake to combat SARS-CoV-2, including their abilities to internalize the virus, release bioactive molecules to interfere with viral infection, and modulate the functions of immune cells. Moreover, we discuss current and potential platelet-targeted therapeutic strategies in controlling COVID-19, including antiplatelet drugs, anticoagulants, and inflammation-targeting treatments. These strategies have shown promise in clinical settings to alleviate the severity of thrombo-inflammatory complications and reduce the mortality rate among COVID-19 patients. In conclusion, an in-depth understanding of platelet-SARS-CoV-2 interactions may uncover novel mechanisms underlying severe COVID-19 complications and could provide new therapeutic avenues for managing this disease.

Identification of a disulfidptosis-related genes signature for prognostic implication in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer. Additionally, disulfidptosis, a newly discovered type of cell death, has been found to be closely associated with the onset and progression of tumors. METHODS: The study first identified genes related to disulfidptosis through correlation analysis. These genes were then screened using univariate cox regression and LASSO regression, and a prognostic model was constructed through multivariate cox regression. A nomogram was also created to predict the prognosis of LUAD. The model was validated in three independent data sets: GSE72094, GSE31210, and GSE37745. Next, patients were grouped based on their median risk score, and differentially expressed genes between the two groups were analyzed. Enrichment analysis, immune infiltration analysis, and drug sensitivity evaluation were also conducted. RESULTS: In this study, we examined 21 genes related to disulfidptosis and developed a gene signature that was found to be associated with a poorer prognosis in LUAD. Our model was validated using three independent datasets and showed AUC values greater than 0.5 at 1, 3, and 5 years. Enrichment analysis revealed that the disulfidptosis-related genes signature had a multifaceted impact on LUAD, particularly in relation to tumor development, proliferation, and metastasis. Patients in the high-risk group exhibited higher tumor purity and lower stromal score, ESTIMATE score, and Immune score. CONCLUSION: This study constructed a gene signature related to disulfidptosis in lung adenocarcinoma and analyzed its impact on the disease and its association with the tumor microenvironment. The findings of this research provide valuable insights into the understanding of lung adenocarcinoma and could potentially lead to the development of new treatment strategies.