Development and validation of a nomogram to predict medication risk based on a knowledge, attitude and practice (KAP) survey of residents in Shanxi Province, China.

Objective: Unsafe medication practices and medication errors are a major cause of harm in healthcare systems around the world. This study aimed to explore the factors that influence the risk of medication and provide medication risk evaluation model for adults in Shanxi province, China. Methods: The data was obtained from the provincial questionnaire from May to December 2022, relying on the random distribution of questionnaires and online questionnaires by four hospitals in Shanxi Province. Multiple linear regression analysis was used to explore the factors affecting the KAP score of residents. Univariate and multivariate logistic regression was used to determine the independent risk factors, and the nomogram was verified by receiver operating characteristic curve, calibration and decision curve analysis. Results: A total of 3,388 questionnaires were collected, including 3,272 valid questionnaires. The average scores of drugs KAP were 63.2 ± 23.04, 33.05 ± 9.60, 23.67 ± 6.75 and 33.16 ± 10.87, respectively. On the evaluation criteria of the questionnaire, knowledge was scored "fair", attitude and practice were scored "good". Sex, monthly income, place of residence, insurance status, education level, and employment were regarded as independent risk factors for medication and a nomogram was established by them. Conclusion: Males, low-income, and low-educated people are important factors affecting the risk of medication. The application of the model can help residents understand the risk of their own medication behavior and reduce the harm of medication.

Interactions between intestinal microbiota and metabolites in zebrafish larvae exposed to polystyrene nanoplastics: Implications for intestinal health and glycolipid metabolism.

Previous studies have shown the harmful effects of nanoscale particles on the intestinal tracts of organisms. However, the specific mechanisms remain unclear. Our present study focused on examining the uptake and distribution of polystyrene nanoplastics (PS-NPs) in zebrafish larvae, as well as its toxic effects on the intestine. It was found that PS-NPs, marked with red fluorescence, primarily accumulated in the intestine section. Subsequently, zebrafish larvae were exposed to normal PS-NPs (0.2-25 mg/L) over a critical 10-day period for intestinal development. Histopathological analysis demonstrated that PS-NPs caused structural changes in the intestine, resulting in inflammation and oxidative stress. Additionally, PS-NPs disrupted the composition of the intestinal microbiota, leading to alterations in the abundance of bacterial genera such as Pseudomonas and Aeromonas, which are associated with intestinal inflammation. Metabolomics analysis showed alterations in metabolites that are primarily involved in glycolipid metabolism. Furthermore, MetOrigin analysis showed a significant correlation between bacterial flora (Pedobacter and Bacillus) and metabolites (D-Glycerate 2-phosphate and D-Glyceraldehyde 3-phosphate), which are related to the glycolysis/gluconeogenesis pathways. These findings were further validated through alterations in multiple biomarkers at various levels. Collectively, our data suggest that PS-NPs may impair the intestinal health, disrupt the intestinal microbiota, and subsequently cause metabolic disorders.

Mechanistic Insights into 1,2-bis(2,4,6-tribromophenoxy)ethane-Induced Male Reproductive Toxicity in Zebrafish.

The novel brominated flame retardant, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), has increasingly been detected in environmental and biota samples. However, limited information is available regarding its toxicity, especially at environmentally relevant concentrations. In the present study, adult male zebrafish were exposed to varying concentrations of BTBPE (0, 0.01, 0.1, 1, and 10 µg/L) for 28 days. The results demonstrated underperformance in mating behavior and reproductive success of male zebrafish when paired with unexposed females. Additionally, a decline in sperm quality was confirmed in BTBPE-exposed male zebrafish, characterized by decreased total motility, decreased progressive motility, and increased morphological malformations. To elucidate the underlying mechanism, an integrated proteomic and phosphoproteomic analysis was performed, revealing a predominant impact on mitochondrial functions at the protein level and a universal response across different cellular compartments at the phosphorylation level. Ultrastructural damage, increased expression of apoptosis-inducing factor, and disordered respiratory chain confirmed the involvement of mitochondrial impairment in zebrafish testes. These findings not only provide valuable insights for future evaluations of the potential risks posed by BTBPE and similar chemicals but also underscore the need for further research into the impact of mitochondrial dysfunction on reproductive health.

A combination of cuproptosis and lncRNAs predicts the prognosis and tumor immune microenvironment in cervical cancer.

BACKGROUND: Cuproptosis induces proteotoxic stress and eventually leads to cell death. However, the relationship between cuproptosis and lncRNAs in cervical cancer has not been fully elucidated. Therefore, we aim to explore the association among lncRNAs, cuproptosis and clinical features in cervical cancer. METHODS: RNA sequencing, genetic mutations, and clinical data of CESC patients were obtained from TCGA. Cuproptosis-associated genes were gathered. WGCNA was used to cluster important modules, and KEGG, GO, GSEA and GSVA were used to explore functional and pathway enrichment. The association between immune microenvironment and cuproptosis-related lncRNAs was performed by using cibersort algorithm and other platforms, including XCELL, TIMER, QUANTISEQ, MCPCOUNTER and EPIC. Fluorescence quantitative PCR was employed to detect the expression of LINC01833 and LINC02321, and CCK-8 and cell scratch assays were used to assess cell proliferation and migration capabilities after LINCRNA interference. RESULTS: 202 upregulated and 45 downregulated lncRNAs were selected. The survival analysis showed that there was a statistically significant difference in survival rates between the high-risk and low-risk groups. The prognosis of tumour mutation burden and the degree of immune infiltration were differed noticeably between the high-risk and low-risk groups. BHG712, TL-2-105, FR-180204, Masitinib, TAK-715, ODI-027, JW-7-24-2, and OSI-930 had substantially higher IC50 values in the high-risk group. Notably, we found AL360178.1 was associated with RNF44 E3 ubiquitin ligase expression. In cervical cancer cell lines, LINC01833 and LINC02321 displayed significant upregulation. Efficient siRNA transfection led to a decreased expression of LINC01833 and LINC02321. This knockdown significantly hindered both cell proliferation and migration capabilities in cervical cancer cells compared to the negative control. CONCLUSION: In conclusion, we constructed five cuprotosis-related lncRNA prognostic models, which may be new tumor therapeutic targets for the prevention and treatment of cervical cancer.

Reproductive and transgenerational toxicity of bisphenol S exposure in pregnant rats: Insights into hormonal imbalance and steroid biosynthesis pathway disruption.

Bisphenol S (BPS) is an alternative chemical to bisphenol A commonly used in food packaging materials. It raises concerns due to potential adverse effects on human health. However, limited evidence exists regarding reproductive toxicity from BPS exposure, and the mechanism of associated transgenerational toxicity remains unclear. In this study, pregnant SD rats were exposed to two different doses of BPS (0.05 or 20 mg/kg) from GD6 to PND21. The objective was to investigate reproductive and transmissible toxicity induced by BPS, explore endocrine effects, and uncover potential underlying mechanisms in rats. Perinatal exposure to BPS in the F0 generation significantly decreased the rate of body weight, ovarian organ coefficient, and growth and development of the F1 generation. Notably, these changes included abnormal increases in body weight and length, estrous cycle disruption, and embryonic dysplasia in F1. 4D-DIA proteomic and PRM analyses revealed that exposure to 20 mg/kg group significantly altered the expression of proteins, such as Lhcgr and Akr1c3, within the steroid biosynthetic pathway. This led to elevated levels of FSH and LH in the blood. The hypothalamic-pituitary-ovarian (HPO) axis, responsible for promoting fertility through the cyclic secretion of gonadotropins and steroid hormones, was affected. RT-qPCR and Western blot results demonstrated that the expression of GnRH in the hypothalamus was decreased, the GnRHR in the pituitary gland was decreased, and the expression of FSHß and LHß in the pituitary gland was increased. Overall, BPS exposure disrupts the HPO axis, hormone levels, and steroid biosynthesis in the ovaries, affecting offspring development and fertility. This study provides new insights into the potential effects of BPS exposure on the reproductive function of the body and its relevant mechanisms of action.

Photodynamic Effect of Vascular-targeted Polyphenol Nanoparticles on Endothelial Cells.

BACKGROUND: Port wine stains (PWS) are vascular malformations, and photodynamic therapy (PDT) is a promising treatment. Emerging drug delivery method employs nanoparticles (NPs) to enhance drug permeability and retention in diseased blood vessels and improving drug bioavailability. (-) -epigallocatechin-3-gallate glycine (EGCG) has anti-angiogenetic effects and boosts photodynamic therapy. Chlorin e6 (Ce6) is capable of efficiently producing singlet oxygen, rendering it a very promising photosensitizer for utilization in nanomedicine. MATERIAL AND METHODS: EGCG-Ce6-NPs were synthesized and characterized using various techniques. The photodynamic effects of EGCG-Ce6-NPs on endothelial cells were evaluated. The compatibility and toxicity of the nanoparticle was tested using the CCK-8 assay. The intracellular uptake of the nanoparticle was observed using an inverted fluorescence microscope, and the intracellular fluorescence intensity was detected using flow cytometry. The ROS generation and apoptosis induced by EGCG-Ce6-NPs was observed using confocal laser scanning microscope and flow cytometry respectively. RESULTS: EGCG-Ce6-NPs exhibited stability, spherical shape of uniform size while reducing the particle diameter, low polydisperse profile and retaining the ability to effectively generate singlet oxygen. These characteristics suggest promising potential for enhancing drug permeability and retention. Additionally, EGCG-Ce6-NPs demonstrated good compatibility with endothelial cells and enhanced intracellular uptake of Chlorin e6. Furthermore, EGCG-Ce6-NPs increased activation efficiency, induced significant toxicity, more reactive oxygen species, and higher rate of late apoptosis after laser irradiation. CONCLUSION: This in vitro study showed the potentials EGCG-Ce6-NPs for the destruction of endothelial cells in vasculature.

Systemic immune-inflammation index is associated with cardiac complications following acute ischemic stroke: A retrospective single-center study.

BACKGROUND: Stroke-induced heart syndrome is a feared complication of ischemic stroke, that is commonly encountered and has a strong association with unfavorable prognosis. More research is needed to explore underlying mechanisms and inform clinical decision making. This study aims to explore the relationship between the early systemic immune-inflammation (SII) index and the cardiac complications after acute ischemic stroke. METHODS: Consecutive patients with acute ischemic stroke were prospectively collected from January 2020 to August 2022 and retrospectively analyzed. We included subjects who presented within 24 hours after symptom onset and were free of detectable infections or cancer on admission. SII index [(neutrophils × platelets/ lymphocytes)/1000] was calculated from laboratory data at admission. RESULTS: A total of 121 patients were included in our study, of which 24 (19.8 %) developed cardiac complications within 14 days following acute ischemic stroke. The SII level was found higher in patients with stroke-heart syndrome (p<.001), which was an independent predictor of stroke-heart syndrome (adjusted odds ratio 5.089, p=.002). CONCLUSION: New-onset cardiovascular complications diagnosed following a stroke are very common and are associated with early SII index.

SEPT3 as a Potential Molecular Target of Triple-Negative Breast Cancer.

Background: The survival rate for triple-negative breast cancer (TNBC) is very low due to its advanced metastatic and aggressive nature, and there is no specific target to improve the survival rate. The expression and clinical signature of neuronal-specific septin-3 (Septin3, SEPT3) in TNBC remain undetermined. Methods: SEPT3 differential expression in TNBC was detected with the use of bioinformatic approaches based on TCGA and GEO database, which was verified with immunohistochemistry in TNBC tissues. Next, the effect of SEPT3 on survival and the association between SEPT3 expression and clinical characteristics were assessed for TNBC patients. We performed Cox analysis to evaluate whether SEPT3 is an independent predictor for TNBC patients. Results: SEPT3 was identified as a key differentially expressed gene. SEPT3 was observed to be elevated in 112 TNBC significantly. Increased expression of SEPT3 contributed to an unfavorable prognosis in patients with TNBC. Additionally, SEPT3 was associated with several factors including TNM stage, lymph node metastasis, Ki67 level and histological grade. SEPT3 was determined to be an independent risk factor for TNBC patients through Cox regression analysis. Conclusion: This study demonstrated that SEPT3 could be a potential disease marker for TNBC patients by bioinformatics analysis and validation in clinical samples.

Healthier Dietary Patterns Are Associated with Better Sleep Quality among Shanghai Suburban Adults: A Cross-Sectional Study.

BACKGROUND: More is to be explored between dietary patterns and sleep quality in the Chinese adult population. METHODS: A cross-sectional study including 7987 Shanghai suburban adults aged 20-74 years was conducted. Dietary information was obtained using a validated food frequency questionnaire. Adherence to a priori dietary patterns, such as the Chinese Healthy Eating Index (CHEI), Dietary Approaches to Stop Hypertension (DASH) diet and Mediterranean diet (MD), was assessed. Sleep quality was assessed from self-reported responses to the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Logistic regression models adjusting for confounders were employed to examine the associations. RESULTS: The overall prevalence of poor sleep (PSQI score ≥ 5) was 28.46%. Factor analysis demonstrated four a posteriori dietary patterns. Participants with a higher CHEI (ORQ4 vs. Q1: 0.81, 95% CI: 0.70-0.95), DASH (ORQ4 vs. Q1: 0.70, 95% CI: 0.60-0.82) or MD (ORQ4 vs. Q1: 0.75, 95% CI: 0.64-0.87) had a lower poor sleep prevalence, while participants with a higher "Beverages" score had a higher poor sleep prevalence (ORQ4 vs. Q1: 1.18, 95% CI: 1.02-1.27). CONCLUSIONS: In Shanghai suburban adults, healthier dietary patterns and lower consumption of beverages were associated with better sleep quality.

Prenatal co-exposure to diisodecyl phthalate and ozone contribute to depressive behavior in offspring mice through oxidative stress and TWIST1 participation.

Exposure to diisodecyl phthalate (DIDP) during early pregnancy may be a risk factor for depressive behavior in offspring. While ozone (O3) exposure also raises the probability of depressive behavior during the preceding DIDP-induced process. In the present study, we investigated the effects of prenatal exposure to DIDP and O3 on the development of depressive-like behavior in offspring mice. The study found that prenatal exposure to both DIDP and O3 significantly increased depressive-like behavior in the offspring mice compared to either DIDP or O3 alone. Prenatal exposure to DIDP and O3 obviously increased the levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol, and decreased the levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the brain tissues of offspring mice. Transcriptome analysis further revealed significant alterations in genes related to oxidative stress and TWIST1 (a helix-loop-helix transcription factor) in response to the combined exposure to DIDP and O3. HPA axis activation, dysregulation of neurodevelopmental factors, oxidative stress and TWIST1 involvement, collectively contributed to the development of depression-like behaviors in offspring mice following prenatal exposure to DIDP and O3. Moreover, the study also verified the potential role of oxidative stress using vitamin E as an antioxidant. The findings provide valuable evidence for the relationship between co-exposure to DIDP and O3 and depression, highlighting the importance of considering the combined effects of multiple environmental pollutants in assessing their impact on mental health outcomes.

Long noncoding RNA small nucleolar RNA host genes as prognostic molecular biomarkers in hepatocellular carcinoma: A meta-analysis.

BACKGROUND: Recently, increasing data have suggested that the lncRNA small nucleolar RNA host genes (SNHGs) were aberrantly expressed in hepatocellular carcinoma (HCC), but the association between the prognosis of HCC and their expression remained unclear. The purpose of this meta-analysis was to determine the prognostic significance of lncRNA SNHGs in HCC. METHODS: We systematically searched Embase, Web of Science, PubMed, and Cochrane Library for eligible articles published up to February 2024. The prognostic significance of SNHGs in HCC was evaluated by hazard ratios (HRs) and 95% confidence intervals (CIs). Odds ratios (ORs) were used to assess the clinicopathological features of SNHGs. RESULTS: This analysis comprised a total of 25 studies covering 2314 patients with HCC. The findings demonstrated that over-expressed SNHGs were associated with larger tumor size, multiple tumor numbers, poor histologic grade, earlier lymphatic metastasis, vein invasion, advanced tumor stage, portal vein tumor thrombosis (PVTT), and higher alpha-fetoprotein (AFP) level, but not with hepatitis B virus (HBV) infection, and cirrhosis. In terms of prognosis, patients with higher SNHG expression were more likely to have shorter overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS). CONCLUSIONS: In conclusion, upregulation of SNHGs expression correlates with shorter OS, RFS, DFS, tumor size and numbers, histologic grade, lymphatic metastasis, vein invasion, tumor stage, PVTT, and AFP level, suggesting that SNHGs may serve as prognostic biomarkers in HCC.

Binary Nano-inhalant Formulation of Icariin Enhances Cognitive Function in Vascular Dementia via BDNF/TrkB Signaling and Anti-inflammatory Effects.

Vascular dementia (VaD) has a serious impact on the patients' quality of life. Icariin (Ica) possesses neuroprotective potential for treating VaD, yet its oral bioavailability and blood-brain barrier (BBB) permeability remain challenges. This research introduced a PEG-PLGA-loaded chitosan hydrogel-based binary formulation tailored for intranasal delivery, enhancing the intracerebral delivery efficacy of neuroprotective agents. The formulation underwent optimization to facilitate BBB crossing, with examinations conducted on its particle size, morphology, drug-loading capacity, in vitro release, and biodistribution. Using the bilateral common carotid artery occlusion (BCCAO) rat model, the therapeutic efficacy of this binary formulation was assessed against chitosan hydrogel and PEG-PLGA nanoparticles loaded with Ica. Post-intranasal administration, enhanced cognitive function was evident in chronic cerebral hypoperfusion (CCH) rats. Further mechanistic evaluations, utilizing immunohistochemistry (IHC), RT-PCR, and ELISA, revealed augmented transcription of synaptic plasticity-associated proteins like SYP and PSD-95, and a marked reduction in hippocampal inflammatory markers such as IL-1ß and TNF-α, highlighting the formulation's promise in alleviating cognitive impairment. The brain-derived neurotrophic factor (BDNF)/tropomyosin related kinase B (TrkB) pathway was activated significantly in the binary formulation compared with the other two. Our study demonstrates that the intranasal application of chitosan hydrogel loaded with Ica-encapsulated PEG-PLGA could effectively deliver Ica into the brain and enhance its neuroprotective effect.

Bis(2-ethylhexyl)-tetrabromophthalate Poses a Higher Exposure Risk and Induces Gender-Specific Metabolic Disruptions in Zebrafish Liver.

Bis(2-ethylhexyl)-tetrabromophthalate (TBPH), a typical novel brominated flame retardant, has been ubiquitously identified in various environmental and biotic media. Consequently, there is an urgent need for precise risk assessment based on a comprehensive understanding of internal exposure and the corresponding toxic effects on specific tissues. In this study, we first investigated the toxicokinetic characteristics of TBPH in different tissues using the classical pseudo-first-order toxicokinetic model. We found that TBPH was prone to accumulate in the liver rather than in the gonad, brain, and muscle of both female and male zebrafish, highlighting a higher internal exposure risk for the liver. Furthermore, long-term exposure to TBPH at environmentally relevant concentrations led to increased visceral fat accumulation, signaling potential abnormal liver function. Hepatic transcriptome analysis predominantly implicated glycolipid metabolism pathways. However, alterations in the profile of associated genes and biochemical indicators revealed gender-specific responses following TBPH exposure. Besides, histopathological observations as well as the inflammatory response in the liver confirmed the development of nonalcoholic fatty liver disease, particularly in male zebrafish. Altogether, our findings highlight a higher internal exposure risk for the liver, enhancing our understanding of the gender-specific metabolic-disrupting potential associated with TBPH exposure.

Persulfate-Promoted Carbamoylation/Cyclization of Alkenes: Synthesis of Amide-Containing Quinazolinones.

The incorporation of amide groups into biologically active molecules has been proven to be an efficient strategy for drug design and discovery. In this study, we present a simple and practical method for the synthesis of amide-containing quinazolin-4(3H)-ones under transition-metal-free conditions. This is achieved through a carbamoyl-radical-triggered cascade cyclization of N3-alkenyl-tethered quinazolinones. Notably, the carbamoyl radical is generated in situ from the oxidative decarboxylative process of oxamic acids in the presence of (NH4)2S2O8.

Chemometrics combined with comprehensive two-dimensional gas chromatography-mass spectrometry for the identification of Baijiu vintage.

The identification of baijiu vintage is crucial for quality assessment and economic value determination. However, its complex composition and multifaceted influences pose significant technical challenges, necessitating research into its aging mechanisms and the development of related identification methods. This study utilized Chemometrics in conjunction with GC × GC-TOFMS for Baijiu Vintage identification. Data compression achieved a reduction of over 1000-fold without compromising key information, enabling analysis on many samples and get their changing regular in a big matrix by MCR. Subsequently, MCR-ALS facilitated the extraction of physical and chemical meaningful information related to baijiu vintage. Key MCR principal components suitable for qualitative and quantitative assessments were selected using CARS-PLS. The regression model demonstrated errors of less than one year. Furthermore, a PLS-DA model provided 30 MCR principal components as potential markers. The research results provide technical support for baijiu vintage identification and lay the groundwork for studying the changing patterns of flavor compounds in baijiu.

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate Enhances foxo1-Mediated Lipophagy to Remodel Lipid Metabolism in Zebrafish Liver.

An emerging environmental contaminant, bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), can bioaccumulate in the liver and affect hepatic lipid metabolism. However, the in-depth mechanism has yet to be comprehensively explored. In this study, we utilized transgenic zebrafish Tg (Apo14: GFP) to image the interference of TBPH on zebrafish liver development and lipid metabolism at the early development stage. Using integrated lipidomic and transcriptomic analyses to profile the lipid remodeling effect, we uncovered the potential effects of TBPH on lipophagy-related signaling pathways in zebrafish larvae. Decreased lipid contents accompanied by enhanced lipophagy were confirmed by the measurements of Oil Red O staining and transmission electron microscopy in liver tissues. Particularly, the regulatory role of the foxo1 factor was validated via its transcriptional inhibitor. Double immunofluorescence staining integrated with biochemical analysis indicated that the enhanced lipophagy and mitochondrial fatty acid oxidation induced by TBPH were reversed by the foxo1 inhibitor. To summarize, our study reveals, for the first time, the essential role of foxo1-mediated lipophagy in TBPH-induced lipid metabolic disorders and hepatoxicity, providing new insights for metabolic disease studies and ecological health risk assessment of TBPH.

Sophoricoside attenuates neuronal injury and altered cognitive function by regulating the LTR-4/NF-κB/PI3K signalling pathway in anaesthetic-exposed neonatal rats.

Introduction: This study examined the protective effects of sophoricoside on neuronal injury and cognitive dysfunction in anaesthetic-exposed neonatal rats. Material and methods: Neuronal injury was induced in rat pups by exposure to isoflurane (0.75%) with 30% oxygen for 6 h on P7. The protective effects of sophoricoside were evaluated by assessing cognitive function using the neurological score and Morris water maze. Neuronal apoptosis was assessed in hippocampus tissue using a TUNEL assay. The cytokine and macrophage inflammatory protein levels were assessed by ELISA. Western blot assays and RT-PCR were performed to assess the expression of NF-κB, TLR-4, Akt, and PI3K proteins in neuronal tissues. Immunohistochemical and histopathological changes were observed in the brain tissues of isoflurane-induced neuronal injury rats. Results: The sophoricoside treatment improved cognitive and neuronal function in rats exposed to isoflurane. Cytokine and MIP levels in the brain tissues of isoflurane-exposed rats decreased. However, sophoricoside treatment attenuated the expression of TLR-4, PI3K, and Akt protein in the brain tissues of isoflurane-exposed rats. The histopathology improved in the sophoricoside-treated isoflurane-exposed rats. Conclusions: Sophoricoside treatment protects against neuronal injury and reduced cognitive function in isoflurane-induced neuronal injury rats by regulating TLR-4 signalling.

Aggravated visual toxicity in zebrafish larvae upon co-exposure to titanium dioxide nanoparticles and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate.

The bioavailability and toxicity of organic pollutants in aquatic organisms can be largely affected by the co-existed nanoparticles. However, the impacts of such combined exposure on the visual system remain largely unknown. Here, we systematically investigated the visual toxicity in zebrafish larvae after single or joint exposure to titanium dioxide nanoparticles (n-TiO2) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) at environmentally relevant levels. Molecular dynamics simulations revealed the enhanced transmembrane capability of the complex than the individual, which accounted for the increased bioavailability of both TBPH and n-TiO2 when combined exposure to zebrafish. Transcriptome analysis showed that co-exposure to n-TiO2 and TBPH interfered with molecular pathways related to eye lens structure and sensory perception of zebrafish. Particularly, n-TiO2 or TBPH significantly suppressed the expression of ßB1-crystallin and rhodopsin in zebrafish retina and lens, which was further enhanced after co-exposure. Moreover, we detected disorganized retinal histology, stunted lens development and significant visual behavioral changes of zebrafish under co-exposure condition. The overall results suggest that combined exposure to water borne n-TiO2 and TBPH increased their bioavailability, resulted in severer damage to optic nerve development and ultimately abnormal visual behavior patterns, highlighting the higher potential health risks of co-exposure to aquatic vertebrates.

Chemotherapy-related symptom networks in distinct subgroups of Chinese patients with gastric cancer.

Objective: This study aims to identify distinct subgroups among gastric cancer patients undergoing chemotherapy (CTX), delineate associated symptom networks, and ascertain the clinical and sociodemographic variables contributing to diverse symptom patterns. Methods: Conducted in eastern China, our investigation involved gastric cancer patients receiving CTX. We gathered data using the M.D. Anderson Symptom Inventory Gastrointestinal Cancer Module along with clinical and sociodemographic variables. Subgroups were discerned based on symptom severity through latent profile analysis, and subsequent comparisons were made regarding the symptom networks in different subgroups. Results: The analysis encompassed 677 eligible gastric cancer patients, revealing three profiles: "Profile 1: low class" (n = 354, 52.3%), "Profile 2: moderate class" (n = 222, 32.8%), and "Profile 3: all high class" (n = 101, 14.9%). Nausea-vomiting exhibited robust associations in the symptom networks of all subgroups, whereas sadness-distress, and taste change-lack of appetite were notably linked with Profile 1 and Profile 2. Distress emerged as a core symptom in Profile 1, lack of appetite dominated the symptom network in Profile 2, and fatigue attained the highest strength in Profile 3. Distinct symptom profiles were influenced by variables such as education level, CTX combined with surgical or herbal treatment, psychological resilience, and social support. Conclusions: Patients within different subgroups manifest individualized patterns of symptom profiles. Analyzing demographics, disease characteristics, and psychosocial information among diverse subgroups facilitates healthcare providers in devising more personalized and targeted symptom management strategies, thereby alleviating the symptom burden on patients.