Accumulation characteristics and fate modeling of phthalic acid esters in surface water from the Three Gorges Reservoir area, China.

Phthalic acid esters (PAEs) are a group of compounds widespread in the environment. To investigate the occurrence and accumulation characteristics of PAEs, surface water samples were collected from the Three Gorges Reservoir area, China. The total concentrations of 11 analyzed PAEs (∑11PAEs) in the collected water samples ranging from 197.7 to 1,409.3 ng/L (mean ± IQR: 583.1 ± 308.4 ng/L). While DEHP was the most frequently detected PAE, DnBP and DnNP were the most predominant PAEs in the analyzed water samples with a mean contribution of 63.3% of the ∑11PAEs. The concentrations of the ∑11PAEs in the water samples from the upper reaches of the Yangtze River were significantly higher than those from the middle reaches. To better understand the transport and fate of the PAEs, seven detected PAEs were modeled by Quantitative Water Air Sediment Interaction (QWASI). The simulated and measured values were close for most PAEs, and differences are within one order of magnitude even for the worst one. For all simulated PAEs, water and particle inflow were main sources in the reservoir, whereas water outflow and degradation in water were important removal pathways. The contribution ratios of different sources/losses varied from PAEs, depending on their properties. The calculated risk quotients of DnNP in the Three Gorges Reservoir area whether based on monitoring or simulating results were all far exceeded the safety threshold value, implying the occurrence of this PAE compound may cause potential adverse effects for the aquatic ecology of the Three Gorges Reservoir area.

Effects of 2,4,6-Trichloroanisole on the morphological development and motility of zebrafish.

2,4,6-Trichloroanisole (2,4,6-TCA), a compound with a characteristic earthy odor, is a common source of odorous pollutants in drinking water and wine. However, research on its biological toxicity is limited. In this study, we used zebrafish as an indicator model to investigate the effects of 2,4,6-TCA exposure on morphological development, oxidative stress, apoptosis, heart rate, blood flow, and motility. We found that exposure to 2,4,6-TCA resulted in significant spinal, tail, and cardiac deformities in zebrafish larvae and promoted a pronounced oxidative stress response and extensive cell apoptosis, notably in the digestive tract, head, spine, and heart, ultimately leading to significant reductions in zebrafish heart rate, blood flow, and motility. Moreover, these effects became more pronounced with an increase in the concentration of 2,4,6-TCA to which the zebrafish were exposed. Furthermore, qPCR analysis revealed that exposure to 2,4,6-TCA promoted significant changes in the expression levels of genes associated with oxidative stress, apoptosis, cardiac development, and the nervous system, particularly key genes (p53, apaf1, casp9, and casp3) in the mitochondrial apoptotic pathway, which were significantly upregulated. Similarly, we detected significant upregulation of ache gene expression. These findings indicated that exposure to 2,4,6-TCA resulted in the accumulation of reactive oxygen species in zebrafish, induced strong oxidative stress responses, and triggered lipid peroxidation and extensive cell apoptosis. Cellular apoptosis, which mitochondrial signaling pathways may mediate, has been found to lead to malformations in zebrafish embryos, resulting in significant reductions in cardiac function and motility. To our knowledge, this is the first systematic assessment of the toxicity of 2,4,6-TCA, and our findings provide an important reference for risk assessment and early warning of 2,4,6-TCA exposure.

Quantitative Proteomics Reveal the Mechanism of MiR-138-5p Suppressing Cervical Cancer via Targeting ZNF385A.

MicroRNAs are short, noncoding RNA molecules that exert pivotal roles in cancer development and progression by modulating various target genes. There is growing evidence that miR-138-5p is significantly involved in cervical cancer (CC). However, its precise molecular mechanism has yet to be fully understood. In the current investigation, a quantitative proteomics approach was utilized to detect possible miR-138-5p targets in HeLa cells systematically. In total, 364 proteins were downregulated, and 150 were upregulated after miR-138-5p overexpression. Bioinformatic analysis of these differentially expressed proteins (DEPs) revealed significant enrichment in several cancer-related pathways. Zinc finger protein 385A (ZNF385A) was determined as a novel direct target of miR-138-5p and discovered to facilitate the proliferation, migration, and cell cycle progression of HeLa cells. SFN and Fas cell surface death receptor(FAS) were then identified as functional downstream effectors of ZNF385A and miR-138-5p. Moreover, a tumor xenograft experiment was conducted to validate the association of miR-138-5p-ZNF385A-SFN/FAS axis with the development of CC in vivo. Our findings have collectively established a catalog of proteins mediated by miR-138-5p and have provided an in-depth comprehension of the molecular mechanisms responsible for the inhibitory effect of miR-138-5p on CC. The miR-138-5p-ZNF385A-SFN/FAS axis could also be beneficial to the identification of new therapeutic targets.

Quantitative Analysis of Primary Compressive Trabeculae Distribution in the Proximal Femur of the Elderly.

OBJECTIVE: As osteoporosis progresses, the primary compressive trabeculae (PCT) in the proximal femur remains preserved and is deemed the principal load-bearing structure that links the femoral head with the femoral neck. This study aims to elucidate the distribution patterns of PCT within the proximal femur in the elderly population, and to assess its implications for the development and optimization of internal fixation devices used in hip fracture surgeries. METHODS: This is a retrospective cohort study conducted from March 2022 to April 2023. A total of 125 patients who underwent bilateral hip joint CT scans in our hospital were enrolled. CT data of the unaffected side of the hip were analyzed. Key parameters regarding the PCT distribution in the proximal femur were measured, including the femoral head's radius (R), the neck-shaft angle (NSA), the angle between the PCT-axis and the head-neck axis (α), the distance from the femoral head center to the PCT-axis (δ), and the lengths of the PCT's bottom and top boundaries (L-bottom and L-top respectively). The impact of gender differences on PCT distribution patterns was also investigated. Student's t-test or Mann-Whitney U test were used to compare continuous variables between genders. The relationship between various variables was investigated through Pearson's correlation analysis. RESULTS: PCT was the most prominent bone structure within the femoral head. The average NSA, α, and δ were 126.85 ± 5.85°, 37.33 ± 4.23°, and 0.39 ± 1.22 mm, respectively, showing no significant gender differences (p > 0.05). Pearson's correlation analysis revealed strong correlations between α and NSA (r = -0.689, p < 0.001), and R and L-top (r = 0.623, p < 0.001), with mild correlations observed between δ and NSA (r = -0.487, p < 0.001), and R and L-bottom (r = 0.427, p < 0.001). Importantly, our study establishes a method to accurately localize PCT distribution in true anteroposterior (AP) radiographs of the hip joint, facilitating precise screw placement in proximal femur fixation procedures. CONCLUSION: Our study provided unprecedented insights into the distribution patterns of PCT in the proximal femur of the elderly population. The distribution of PCT in the proximal femur is predominantly influenced by anatomical and geometric factors, such as NSA and femoral head size, rather than demographic factors like gender. These insights have crucial implications for the design of internal fixation devices and surgical planning, offering objective guidance for the placement of screws in hip fracture treatments.

Circulating Myokines as Novel Biomarkers for Cardiovascular Diseases.

Myokines are a group of cytokines or polypeptides released from skeletal muscle during exercise. Growing evidence suggests that myokines are associated with the development of cardiovascular disease (CVD). Moreover, several myokines in peripheral blood exhibit dynamic changes in different CVD stages. This review summarizes the potential roles of myokines such as myostatin, irisin, brain-derived neurotrophic factor, mitsugumin 53, meteorin-like, and apelin in various CVD, including myocardial infarction, heart failure, atherosclerosis, hypertension, and diabetes. The association of these myokines with biomarkers currently being used in clinical practice is also discussed. Furthermore, the review considers the emerging role of myokines in CVD and addresses the challenges remaining in translating these discoveries into novel clinical biomarkers for CVD.

Development and internal validation of a model for predicting cefoperazone/sulbactam-associated coagulation disorders in Chinese inpatients.

BACKGROUND AND AIM: The use of cefoperazone/sulbactam (CPZ/SAM) could commonly cause vitamin K-dependent coagulation disorders and even hemorrhage sometimes. However, there is a lack of prediction tools estimating the risk for this. This study aimed at developing and internally validating a model for predicting CPZ/SAM-associated coagulation disorders in Chinese inpatients. METHODS: A case-control study was conducted in 11,092 adult inpatients admitted to a Chinese general hospital between 2020 and 2021 and treated with CPZ/SAM. Patients with CPZ/SAM-associated coagulation disorders were identified through the Adverse Drug Events Active Surveillance and Assessment System-II and subsequent manual evaluation. Controls were selected from eligible patients who didn't develop coagulation disorders after CPZ/SAM therapy, with a 1:1 propensity score matching. The final predictors were obtained by univariable and multivariable logistic regression analyses. Internal validation and calibration for the model were performed using 1000 bootstrap resamplings. RESULTS: 258 patients were identified as CPZ/SAM-associated coagulation disorders in 2184 patients eligible for inclusions and exclusions and the incidence was 11.8%. A final population of 252 cases and 252 controls was included for model development and validation. Malnutrition (OR = 2.41 (1.56-3.77)), history of recent bleeding (OR = 1.95 (1.32-2.90)), treatment duration (OR = 1.10 (1.07-1.14)), combination with carbapenems (OR = 4.43 (1.85-11.88)), and serum creatinine (OR = 1.01 (1.00-1.01)) were identified as final predictors. The model showed good discrimination, calibration, and clinical practicality, with the validated area under the receiver operating characteristic curve being 0.723 (0.683-0.770). CONCLUSIONS: The model with good performance quantifies the risk for CPZ/SAM-associated coagulation disorders, and may support individual assessment and interventions to mitigate the risk after external validation.

United under stress: High-speed transport network emerging at bacterial living edge.

Individuals tend to move freely when there is enough room but would act collectively for their survival under external stress. In the case of living cells, for instance, when a drop of low-density flagellated bacterial solution is transferred onto the agar surface, the initially disordered movement of individual bacteria would be replaced with coordinated cell swarming after a lag phase of a few hours. Here, we study how such cooperation is established while overcoming the disorder at the onset of the lag phase with single nanoparticle tracking. Upon the spreading of the droplet, the bacteria in the solution cluster and align near the almost immobilized contact line confining the drop, forming a narrow ring of cells. As individual cells move in and out of the ring continuously, certain flow patterns emerge in the inter-bacterial fluid. We reveal high-speed long-distance unidirectional flows with definite chirality along the outside of the ring, along the inside of the ring and across the ring. We speculate that these flows enable the fast and efficient transport, facilitating the communication and unification of the bacterial community.

Heterologous synthesis of ginsenoside F1 and its precursors in Nicotiana benthamiana.

Ginsenoside F1 has high medicinal values, which is a kind of rare triterpene saponin isolated from Panax plants. The extremely low content of ginsenoside F1 in herbs has limited its research and application in medical field. In this work, we constructed a pathway in tobacco for the biosynthesis of ginsenoside F1 by metabolic engineering. Four enzyme genes (PnDDS, CYP716A47, CYP716S1 and UGT71A56) isolated from Panax notoginseng were introduced into tobacco. Thus, a biosynthetic pathway for ginsenoside F1 synthesis was artificially constructed in tobacco cells; moreover, the four exogenous genes could be expressed in the roots, stems and leaves of transgenic plants. Consequently, ginsenoside F1 and its precursors were successfully synthesized in the transgenic tobacco, compared with Panax plants, the content of ginsenoside F1 in transgenic tobacco was doubled. In addition, accumulation of ginsenoside F1 and its precursors in transgenic tobacco shows organ specificity. Based on these results, a new approach was established to produce rare ginsenoside F1; meanwhile, such strategy could also be employed in plant hosts for the heterologous synthesis of other important or rare natural products.

Levels, Distribution and Ecological Risk Assessment of PBDEs in Soils and Plants Around the Engineering Plastics Factory.

This study systematically investigated the pollution levels and migration trends of PBDEs in soils and plants around engineering plastics factory, and identified the ecological risks of PBDEs in the environment around typical pollution sources.The results showed that 13 kinds of PBDEs were widely detected in the surrounding areas, and the concentration level was higher than the general environmental pollution level. The total PBDE concentrations (∑13PBDEs) in soils ranged from 14.6 to 278.4 ng/g dry weight (dw), and in plants ranged from 11.5 to 176 ng/g dw. Both soil and plant samples showed that BDE-209 was the most important congener, the pollution level in soil and plant was similar, and the composition of PBDEs congener was similar. In the soil column (50 cm), the radial migration of PBDEs was mainly concentrated in the 0-30 cm section. Except for BDE-66, which was mainly located in the 20-30 cm soil layer, the concentration of PBDEs was the highest in the 0-10 cm region. Furthermore, the environmental risks of PBDEs in soil and plants were evaluated by hazard quotient method, and the HQ values were all < 1, which did not exhibit any ecological risk. The evaluation results also showed that the ecological risk of PBDEs in soil was higher than that of plants, especially penta-BDE, which should be paid more attention.

Electrochemical Sensor for the Detection and Accurate Early Diagnosis of Ovarian Cancer.

Ovarian cancer (OC) has the highest mortality rate among malignant tumors, primarily because it is difficult to diagnose early. Exosomes, a type of extracellular vesicle rich in parental information, have garnered significant attention in the field of cancer diagnosis and treatment. They play an important regulatory role in the occurrence, development, and metastasis of OC. Consequently, exosomes have emerged as noninvasive biomarkers for early cancer detection. Therefore, identifying cancer-derived exosomes may offer a novel biomarker for the early detection of OC. In this study, we developed a metal-organic frameworks assembled "double hook"-type aptamer electrochemical sensor, which enables accurate early diagnosis of OC. Under optimal experimental conditions, electrochemical impedance spectroscopy technology demonstrated a good linear relationship within the concentration range of 31-3.1 × 106 particles per microliter, with a detection limit as low as 12 particles per microliter. The universal exosome detection platform is constructed, and this platform can not only differentiate between high-grade serous ovarian cancer (HGSOC) patients and healthy individuals but also distinguish between HGSOC patients and nonhigh-grade serous OC (non-HGSOC). Consequently, it provides a novel strategy for the early diagnosis of OC and holds great significance in clinical differential diagnosis.

Development of a CRISPR/Cas12a-mediated aptasensor for Mpox virus antigen detection.

The emergence and rapid spread of Mpox (formerly monkeypox) have caused significant societal challenges. Adequate and appropriate diagnostics procedures are an urgent necessity. Herein, we discover a pair of aptamers through the systematic evolution of ligands by exponential enrichment (SELEX) that exhibit high affinity and bind to different sites towards the A29 protein of the Mpox virus. Subsequently, we propose a facile, sensitive, convenient CRISPR/Cas12a-mediated aptasensor for detecting the A29 antigen. The procedure employs the bivalent aptamers recognition, which induces the formation of a proximity switch probe and initiates subsequent cascade strand displacement reactions, then triggers CRISPR/Cas12a DNA trans-cleavage to achieve the sensitive detection of Mpox. Our method enables selective and ultrasensitive evaluation of the A29 protein within the range of 1 ng mL-1 to 1 µg mL-1, with a limit of detection (LOD) at 0.28 ng mL-1. Moreover, spiked A29 protein recovery exceeds 96.9%, while the detection activity remains above 91.9% after six months of storage at 4 °C. This aptasensor provides a novel avenue for exploring clinical diagnosis in cases involving Mpox as facilitating development in various analyte sensors.

Identification and Functional Analysis of Lysine 2-Hydroxyisobutyrylation in Cyanobacteria.

Cyanobacteria are the oldest prokaryotic photoautotrophic microorganisms and have evolved complicated post-translational modification (PTM) machinery to respond to environmental stress. Lysine 2-hydroxyisobutyrylation (Khib) is a newly identified PTM that is reported to play important roles in diverse biological processes, however, its distribution and function in cyanobacteria have not been reported. Here, we performed the first systematic studies of Khib in a model cyanobacterium Synechococcus sp. strain PCC 7002 (Syn7002) using peptide prefractionation, pan-Khib antibody enrichment, and high-accuracy mass spectrometry (MS) analysis. A total of 1875 high-confidence Khib sites on 618 proteins were identified, and a large proportion of Khib sites are present on proteins in the cellular metabolism, protein synthesis, and photosynthesis pathways. Using site-directed mutagenesis and functional studies, we showed that Khib of glutaredoxin (Grx) affects the efficiency of the PS II reaction center and H2O2 resistance in Syn7002. Together, this study provides novel insights into the functions of Khib in cyanobacteria and suggests that reversible Khib may influence the stress response and photosynthesis in both cyanobacteria and plants.

Interactome Analysis of ClpX Reveals Its Regulatory Role in Metabolism and Photosynthesis in Cyanobacteria.

Protein homeostasis is essential for cyanobacteria to maintain proper cellular function under adverse and fluctuating conditions. The AAA+ superfamily of proteolytic complexes in cyanobacteria plays a critical role in this process, including ClpXP, which comprises a hexameric ATPase ClpX and a tetradecameric peptidase ClpP. Despite the physiological effects of ClpX on growth and photosynthesis, its potential substrates and underlying mechanisms in cyanobacteria remain unknown. In this study, we employed a streptavidin-biotin affinity pull-down assay coupled with label-free proteome quantitation to analyze the interactome of ClpX in the model cyanobacterium Synechocystis sp. PCC 6803 (hereafter Synechocystis). We identified 503 proteins as potential ClpX-binding targets, many of which had novel interactions. These ClpX-binding targets were found to be involved in various biological processes, with particular enrichment in metabolic processes and photosynthesis. Using protein-protein docking, GST pull-down, and biolayer interferometry assays, we confirmed the direct association of ClpX with the photosynthetic proteins, ferredoxin-NADP+ oxidoreductase (FNR) and phycocyanin subunit (CpcA). Subsequent functional investigations revealed that ClpX participates in the maintenance of FNR homeostasis and functionality in Synechocystis grown under different light conditions. Overall, our study provides a comprehensive understanding of the extensive functions regulated by ClpX in cyanobacteria to maintain protein homeostasis and adapt to environmental challenges.

Growing attention on the toxicity of Chinese herbal medicine: a bibliometric analysis from 2013 to 2022.

Introduction: Despite the clinical value of Chinese herbal medicine (CHM), restricted comprehension of its toxicity limits the secure and efficacious application. Previous studies primarily focused on exploring specific toxicities within CHM, without providing an overview of CHM's toxicity. The absence of a quantitative assessment of focal points renders the future research trajectory ambiguous. Therefore, this study aimed to reveal research trends and areas of concern for the past decade. Methods: A cross-sectional study was conducted on publications related to CHM and toxicity over the past decade from Web of Science Core Collection database. The characteristics of the publication included publication year, journal, institution, funding, keywords, and citation counts were recorded. Co-occurrence analysis and trend topic analysis based on bibliometric analysis were conducted on keywords and citations. Results: A total of 3,225 publications were analyzed. Number of annal publications increased over the years, with the highest number observed in 2022 (n = 475). The Journal of Ethnopharmacology published the most publications (n = 425). The most frequently used toxicity classifications in keywords were hepatotoxicity (n = 119) or drug-induced liver injury (n = 48), and nephrotoxicity (n = 40). Co-occurrence analysis revealed relatively loose connections between CHM and toxicity, and their derivatives. Keywords emerging from trend topic analysis for the past 3 years (2019-2022) included ferroptosis, NLRP3 inflammasome, machine learning, network pharmacology, traditional uses, and pharmacology. Conclusion: Concerns about the toxicity of CHM have increased in the past decade. However, there remains insufficient studies that directly explore the intersection of CHM and toxicity. Hepatotoxicity and nephrotoxicity, as the most concerned toxicity classifications associated with CHM, warrant more in-depth investigations. Apoptosis was the most concerned toxicological mechanism. As a recent increase in attention, exploring the mechanisms of ferroptosis in nephrotoxicity and NLRP3 inflammasome in hepatotoxicity could provide valuable insights. Machine learning and network pharmacology are potential methods for future studies.

Deciphering the structure, function, and mechanism of lysine acetyltransferase cGNAT2 in cyanobacteria.

Lysine acetylation is a conserved regulatory posttranslational protein modification that is performed by lysine acetyltransferases (KATs). By catalyzing the transfer of acetyl groups to substrate proteins, KATs play critical regulatory roles in all domains of life; however, no KATs have yet been identified in cyanobacteria. Here, we tested all predicted KATs in the cyanobacterium Synechococcus sp. PCC 7002 (Syn7002) and demonstrated that A1596, which we named cyanobacterial Gcn5-related N-acetyltransferase (cGNAT2), can catalyze lysine acetylation in vivo and in vitro. Eight amino acid residues were identified as the key residues in the putative active site of cGNAT2, as indicated by structural simulation and site-directed mutagenesis. The loss of cGNAT2 altered both growth and photosynthetic electron transport in Syn7002. In addition, quantitative analysis of the lysine acetylome identified 548 endogenous substrates of cGNAT2 in Syn7002. We further demonstrated that cGNAT2 can acetylate NAD(P)H dehydrogenase J (NdhJ) in vivo and in vitro, with the inability to acetylate K89 residues, thus decreasing NdhJ activity and affecting both growth and electron transport in Syn7002. In summary, this study identified a KAT in cyanobacteria and revealed that cGNAT2 regulates growth and photosynthesis in Syn7002 through an acetylation-mediated mechanism.

Adhesion G Protein-Coupled Receptor G2 Promotes Hepatocellular Carcinoma Progression and Serves as a Neutrophil-Related Prognostic Biomarker.

Adhesion G protein-coupled receptor G2 (ADGRG2) is an orphan adhesion G protein-coupled receptor (GPCR), which performs a tumor-promoting role in certain cancers; however, it has not been systematically investigated in hepatocellular carcinoma (HCC). In the current study, we utilized multiple databases to analyze the expression and diagnostic and prognostic value of ADGRG2 in HCC and its correlation with immune infiltration and inflammatory factors. The function and upstream regulatory miRNA of ADGRG2 were validated through qPCR, Western blot, CCK8, wound healing, and dual luciferase assays. It turned out that ADGRG2 was significantly higher in HCC and had a poor survival rate, especially in AFP ≤ 400 ng/mL subgroups. Functional enrichment analysis suggested that ADGRG2 may be involved in cancer pathways and immune-related pathways. In vitro, siRNA-mediated ADGRG2 silencing could inhibit the proliferation and migration of Huh7 and HepG2 cells. There was a highly significant positive correlation between ADGRG2 and neutrophils. Moreover, NET-related genes were filtered and confirmed, such as ENO1 and S100A9. Meanwhile, the high expression of ADGRG2 was also accompanied by the highest number of inflammatory cytokines, chemokines, and chemokine receptors and good immunotherapy efficacy. Finally, AGDGR2 may be sensitive to two drugs (PIK-93 and NPK76-II-72-1) and can be targeted by miR-326. In conclusion, ADGRG2 may serve as a novel biomarker and drug target for HCC diagnosis, immunotherapy, and prognosis and was related to neutrophils and the inflammatory process of liver cancer development.

Rapid Genotyping of Campylobacter coli Strains from Poultry Meat by PFGE, Sau-PCR, and fla-DGGE.

The genotyping of Campylobacter coli was done using three methods, pulsed-field gel electrophoresis (PFGE), Sau-polymerase chain reaction (Sau-PCR), and denaturing gradient gel electrophoresis assay of flagellin gene (fla-DGGE) and the characteristics of these assays were compared. The results showed that a total of 53 strains of C. coli were isolated from chicken and duck samples in three markets. All isolates were clustered into 31, 33, and 15 different patterns with Simpson's index of diversity (SID) values of 0.972, 0.974, and 0.919, respectively. Sau-PCR assay was simpler, more rapid, and had higher discriminatory power than PFGE assay. Fla-DGGE assay could detect and illustrate the number of contamination types of C. jejuni and C. coli without cultivation, which saved more time and cost than Sau-PCR and PFGE assays. Therefore, Sau-PCR and fla-DGGE assays are both rapid, economical, and easy to perform, which have the potential to be promising and accessible for primary laboratories in genotyping C. coli strains.

TMBPF-induced neurotoxicity and oxidative stress in zebrafish larvae: impacts on central nervous system development and dopamine neurons.

Bisphenol A (BPA), a common bisphenol molecule, is well known in the environment as an endocrine disruptor. Furthermore, BPs (BPA, BPS, BPF, and BPAF) have been shown in recent years to be neurotoxic to zebrafish. Tetramethyl bisphenol F (TMBPF) has recently been introduced as a substitute for bisphenol A (BPA) in various industries, including plastics and food contact coatings. However, a growing number of studies have demonstrated that the toxicity of some BPA substitutes is similar to or even stronger than BPA, posing potential harm to human health and the environment. In this study, we used zebrafish larvae as a model to investigate the neurodevelopmental effects of TMBPF at different concentrations (0, 0.25, 0.5, 1, 2, 4 and 8 mg/L). Our results showed that exposure to TMBPF at concentrations higher than 4 mg/L for 72 h post-fertilization (hpf) resulted in zebrafish mortality, whereas exposure to 2 mg/L for 144 hpf caused deformities. Furthermore, TMBPF exposure inhibited the development of the central nervous system, motor nerves, and dopamine neurons in zebrafish. Real-time polymerase chain reaction (PCR) analysis revealed that TMBPF exposure significantly down-regulated the expression of oxidative stress-related genes (Cu/Zn-SOD, Mn-SOD, and CAT) and neurodevelopmental genes (mbp, gafp, and syn2a), while up-regulated the expression of dopamine-related genes (th1, th2, and dat). Notably, treatment with the antioxidant N-acetylcysteine (NAC) alleviated TMBPF-induced toxicity. NAC can regulate the expression of genes related to oxidative stress, neurodevelopment and dopamine development, and make the nerve development of zebrafish normal. Overall, our research suggested that TMBPF may disrupt the development of the early central nervous system and dopamine neurons, leading to abnormal motor behavior in zebrafish larvae. These results highlight the potential risks associated with the use of TMBPF in various industries and the importance to evaluate its potential risks to human health and the environment.

7,8,3'-Trihydroxyflavone prevents doxorubicin-induced cardiotoxicity and mitochondrial dysfunction via activating Akt signaling pathway in H9c2 cells.

Clinical application of the widely used chemotherapeutic agent, doxorubicin (DOX), is limited by its cardiotoxicity. Mitochondrial dysfunction has been revealed as a crucial factor in DOX-induced cardiotoxicity. 7,8,3'-Trihydroxyflavone (THF) is a mimetic brain-derived neurotrophic factor with neuroprotective effects. However, the potential effects of THF on DOX-induced cardiomyocyte damage and mitochondrial disorders remain unclear. H9c2 cardiomyoblasts were exposed to DOX and/or THF at different concentrations. Cardiomyocyte injury was evaluated using lactate dehydrogenase (LDH) assay and Live/Dead cytotoxicity kit. Meanwhile, mitochondrial membrane potential (MMP), morphology, mitochondrial reactive oxygen species (mito-ROS) production, and the oxygen consumption rate of cardiomyocytes were measured. The protein levels of key mitochondria-related factors such as adenosine monophosphate-activated protein kinase (AMPK), mitofusin 2 (Mfn2), dynamin-related protein 1 (Drp1), and optic atrophy protein 1 (OPA1) were examined. We found that THF reduced LDH content and death ratio of DOX-treated cardiomyocytes in a concentration-dependent manner, while increasing MMP without significantly affecting the routine and maximum capacity of mitochondrial respiration. Mechanistically, THF increased the activity of Akt and protein levels of Mfn2 and heme oxygenase 1 (HO-1). Moreover, inhibition of Akt reversed the protective role of THF, increased mito-ROS levels, and repressed Mfn2 and HO-1 expression. Therefore, we conclude, THF relieves DOX-induced cardiotoxicity and improves mitochondrial function by activating Akt-mediated Mfn2 and HO-1 pathways. This finding provides promising therapeutic insights for DOX-induced cardiac dysfunction.

Extract latent features of single-particle trajectories with historical experience learning.

Single-particle tracking has enabled real-time, in situ quantitative studies of complex systems. However, inferring dynamic state changes from noisy and undersampling trajectories encounters challenges. Here, we introduce a data-driven method for extracting features of subtrajectories with historical experience learning (Deep-SEES), where a single-particle tracking analysis pipeline based on a self-supervised architecture automatically searches for the latent space, allowing effective segmentation of the underlying states from noisy trajectories without prior knowledge on the particle dynamics. We validated our method on a variety of noisy simulated and experimental data. Our results showed that the method can faithfully capture both stable states and their dynamic switch. In highly random systems, our method outperformed commonly used unsupervised methods in inferring motion states, which is important for understanding nanoparticles interacting with living cell membranes, active enzymes, and liquid-liquid phase separation. Self-generating latent features of trajectories could potentially improve the understanding, estimation, and prediction of many complex systems.