Biological Toxic Effects Research Articles

Metabolomic Profiling and Network Toxicology: Mechanistic Insights into Effect of Gossypol Acetate Isomers in Uterine Fibroids and Liver Injury

Objective: Gossypol is a natural polyphenolic dialdehyde product that is primarily isolated from cottonseed. It is a racemized mixture of (−)-gossypol and (+)-gossypol that has anti-infection, antimalarial, antiviral, antifertility, antitumor and antioxidant activities, among others. Gossypol optical isomers have been reported to differ in their biological activities and toxic effects. Method: In this study, we performed a metabolomics analysis of rat serum using 1H-NMR technology to investigate gossypol optical isomers’ mechanism of action on uterine fibroids. Network toxicology was used to explore the mechanism of the liver injury caused by gossypol optical isomers. SD rats were randomly divided into a normal control group; model control group; a drug-positive group (compound gossypol acetate tablets); high-, medium- and low-dose (−)-gossypol acetate groups; and high-, medium- and low-dose (+)-gossypol acetate groups. Result: Serum metabolomics showed that gossypol optical isomers’ pharmacodynamic effect on rats’ uterine fibroids affected their lactic acid, cholesterol, leucine, alanine, glutamate, glutamine, arginine, proline, glucose, etc. According to network toxicology, the targets of the liver injury caused by gossypol optical isomers included HSP90AA1, SRC, MAPK1, AKT1, EGFR, BCL2, CASP3, etc. KEGG enrichment showed that the toxicity mechanism may be related to pathways active in cancer, such as the PPAR signaling pathway, glycolysis/glycolysis gluconeogenesis, Th17 cell differentiation, and 91 other closely related signaling pathways. Conclusions: (−)-gossypol acetate and (+)-gossypol acetate play positive roles in the treatment and prevention of uterine fibroids. Gossypol optical isomers cause liver damage through multiple targets and pathways.

Application of the Biological Toxicity Effect Ratio (BER) Method for Advancing Water Quality Criteria Derivation.

Water quality criteria (WQC) serve as a scientific foundation for pollutant risk assessment and control in aquatic ecosystems. The development of regionally differentiated WQC tailored to specific regional characteristics has become an emerging trend. However, the current WQC is constrained by a lack of regional species toxicity data. To address these limitations, this study proposes the biological toxicity effect ratio (BER) method, which indirectly reflects the toxicity sensitivity of the overall aquatic ecosystem through the toxicity information on a limited number of species, enabling rapid WQC prediction. Using the established WQC in China and the USA as a case study, we combined mathematical derivation and data validation to evaluate the BER method. Among various species-taxon groups of freshwater organisms, planktonic crustaceans demonstrated the highest predictive accuracy. Our analysis further revealed that species toxicity sensitivity and regional variability jointly influence the prediction accuracy. Regardless of the evaluation indexes, planktonic crustaceans emerged as the most suitable species-taxon group for the BER method. Additionally, the BER method is particularly applicable to pollutants with conserved mechanisms across species. This study systematically explores the feasibility of using the BER method and offers new insights for deriving regionally differentiated WQC.

3,4-difluoro-2-(((4-phenoxyphenyl)imino)methyl)phenol with in silico predictions: Synthesis, spectral analyses, ADME studies, targets and biological activity, toxicity and adverse effects, site of metabolism, taste activity

In this study, a fluorinated Schiff base compound, named 3,4-difluoro-2-(((4-phenoxy phenyl)imino)methyl)phenol, was synthesized using the precursor compounds 4-phenoxyaniline and 2,3-difluoro-6-hydroxybenzaldehyde. This study aims to characterize the synthesized Schiff base and its structural properties and to investigate its pharmaceutical suitability. X-ray, 1H NMR, UV–vis, and FTIR spectroscopy were used to characterize the synthesized compound. The leading pharmaceutical properties investigated in this study include physicochemical properties, ADME analyses, target identification, prediction of biological activity, absorption in human gastrointestinal tract, blood-brain barrier permeability, drug classification, adverse and toxic effects, phase I and phase II metabolism, sites of metabolism and organoleptic properties. This paper also includes applications of many CADD methods that can be applied to small molecules. The results of the study show that the title compound has moderate physicochemical and ADME properties, moderate toxic and adverse effects, suitable intestinal absorption, and unsuitable BBB permeation. The most potential target of the title compound is the endoplasmic reticulum-associated amyloid-beta peptide-binding protein. The primary cleavage sites of the title compound are the oxygen atom in the phenol group, the nitrogen atom in the amine group, and the oxygen atom in the diphenyl ether.

Development of a Supermolecular Radionuclide-Drug Conjugate System for Integrated Radiotheranostics for Non-small Cell Lung Cancer.

Radionuclide-drug conjugates (RDCs) designed from small molecule or nanoplatform shows complementary characteristics. We constructed a new RDC system with integrated merits of small molecule and nanoplatform-based RDCs. Erlotinib was labeled with 131I to construct the bulk of RDC (131I-ER). Floxuridine was mixed with 131I-ER to develop a hydrogen bond-driving supermolecular RDC system (131I-ER-Fu NPs). The carrier-free 131I-ER-Fu NPs supermolecule not only demonstrated integrated merits of small molecule and nanoplatform-based RDC, including clear structure definition, stable quality control, prolonged circulation lifetime, enhanced tumor specificity and retention, and rapidly nontarget clearance, but also exhibited low biological toxicity and stronger antitumor effects. In vivo imaging also revealed its application for tumor localization of nonsmall cell lung cancer (NSCLC) and screening of patients suitable for epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. We considered that 131I-ER-Fu NPs showed potentials as an integrated platform for the radiotheranostics of NSCLC.

Effects of microplastics on the kidneys: a narrative review

Micro- and nanoplastics (MPs) are small synthetic organic polymer particles (<5 mm and <1 μm, respectively) that originate directly from plastic compounds or result from the degradation of plastic. These particles are a global concern since they are widely distributed in water, air, food and soil, and recent scientific evidence has linked MPs to negative biological effects. Although these particles are difficult to detect in humans, MPs have been identified in different biological fluids and tissues, such as the placenta, lung, intestines, liver, blood, urine, and kidneys. Human exposure to MPs can occur by ingestion, inhalation, or dermal contact, potentially causing metabolic alterations. Data from experimental and clinical studies have revealed that the ability of MPs to promote inflammation, oxidative stress, and organ dysfunction and negatively affect clinical outcomes is associated with their accumulation in body fluids and tissues. Although evidence of the putative action of MPs in the human kidney is still scarce, there is growing interest in studying MPs in this organ. In addition, chronic kidney disease (CKD) requires investigation because this condition is potentially prone to MP accumulation. The purpose of the present article is (i) to review the general aspects of MP generation, available analytic methods for identification and the main known biological toxic effects and (ii) to describe and critically analyze key experimental and clinical studies that support a role of MPs in kidney disease.

Unraveling the toxicity response and metabolic compensation mechanism of tannic acid-Cr(III) complex on alga Raphidocelis subcapitata

Due to their assembly properties and variable molecular weights, the potential biological toxicity effects of macromolecular organic ligand heavy metal complexes are more difficult to predict and their mechanisms are more complex. This study unraveled the toxicity response and metabolic compensation mechanism of tannic acid-Cr(III) (TA-Cr(III)) complex on alga Raphidocelis subcapitata using multi-omics approaches. Results showed TA-Cr(III) complex caused oxidative damage and photosystem disruption, destroying the cell morphology and inhibiting algal growth by >80 % at high exposure levels. TA-Cr(III) complex stress down-regulated proteins linked to proliferation, photosynthesis and antioxidation while upregulating carbon fixation, TCA cycle and amino acid metabolism. The increase of fumarate, citrate, isocitrate and semialdehyde succinate was validated by metabolomics analysis, which improved the TCA cycle, amino acid metabolism and carbon fixation. Activation of the above cellular processes somewhat compensated for the inhibition of algal photosynthesis by TA-Cr(III) complex exposure. In conclusion, physiological toxicity coupled with downstream metabolic compensation in response to Cr(III) complex of macromolecular was characterized in Raphidocelis subcapitata, unveiling the adaptive mechanism of algae under the stress of heavy metal complexes with macromolecular organic ligands.

Enantioselective Toxicity of Tetramethrin to Different Developmental Stages of Zebrafish (Danio rerio).

Chiral pesticides exhibit enantioselective differences in processes such as biological absorption, metabolism, and toxic effects. Organisms have different physiological characteristics at different developmental stages. Therefore, conducting enantiomeric toxicity studies at different developmental stages of organisms can help deepen the understanding of the ecological effects of chiral pesticides. This study focused on trans-tetramethrin (Tet) and investigated the enantioselectivity in bioconcentration, developmental toxicity, estrogenic effects, and immunotoxicity of Tet's racemate ((±)-Tet) and its two enantiomers ((+)-Tet and (-)-Tet) in three developmental stages of zebrafish: embryos, yolk sac larvae, and juveniles. The results showed that Tet exhibited different enantioselectivity in lethal, bioconcentration, and teratogenic effects on zebrafish at different developmental stages. The LC50 value was (+)-Tet > (±)-Tet > (-)-Tet, with embryos being the most sensitive, followed by juveniles and yolk sac larvae. The enantioselective bioconcentration was (±)-Tet > (+)-Tet > (-)-Tet, and the bioconcentration effect was greater in embryos than that in yolk sac larvae and juveniles. Developmental toxicity indicated that (+)-Tet and (±)-Tet had higher teratogenic effects on yolk sac larvae than on embryos. Tet exhibited different enantioselective effects on the expression of zebrafish estrogen-related genes and innate immune-related genes at different developmental stages. These results will contribute to a more comprehensive assessment of the aquatic toxicity and environmental risks of chiral pesticides.

Carbon Nanomaterials for Biomedical Applications: Progress and Outlook.

Recent developments in nanoscale materials have found extensive use in various fields, especially in the biomedical industry. Several substantial obstacles must be overcome, particularly those related to nanostructured materials in biomedicine, before they can be used in therapeutic applications. Significant concerns in biomedicine include biological processes, adaptability, toxic effects, and nano-biointerfacial properties. Biomedical researchers have difficulty choosing suitable materials for drug carriers, cancer treatment, and antiviral uses. Carbon nanomaterials are among the various nanoparticle forms that are continually receiving interest for biomedical applications. They are suitable materials owing to their distinctive physical and chemical properties, such as electrical, high-temperature, mechanical, and optical diversification. An individualized, controlled, dependable, low-carcinogenic, target-specific drug delivery system can diagnose and treat infections in biomedical applications. The variety of carbon materials at the nanoscale is remarkable. Allotropes and other forms of the same element, carbon, are represented in nanoscale dimensions. These show promise for a wide range of applications. Carbon nanostructured materials with exceptional mechanical, electrical, and thermal properties include graphene and carbon nanotubes. They can potentially revolutionize industries, including electronics, energy, and medicine. Ongoing investigation and expansion efforts continue to unlock possibilities for these materials, making them a key player in shaping the future of advanced technology. Carbon nanostructured materials explore the potential positive effects of reducing the greenhouse effect. The current state of nanostructured materials in the biomedical sector is covered in this review, along with their synthesis techniques and potential uses.

Combined pollution characteristics and ecological risks of multi-pollutants in Poyang Lake

Poyang Lake, the largest freshwater lake in China, faced severe ecological degradation in the past decade. Combined pollution of multi-pollutants may be one of the contributing factors. However, the characteristics of combined pollution and the ecological risks are still not clear. In this study, we used Polar Organic Chemical Integrative Sampler (POCIS), In Situ Bioassay Passive Sampling Device (ISBPSD) and conventional sampling methods, to study the toxic pollutants levels and the combined biological toxicity effects. The results showed that high levels of organochlorine pesticides (OCPs, averaged 162 ng/g) and polycyclic musk (PCM, averaged 53.6 ng/g) residues, as well as some metals such as nickel (Ni), lead (Pb) concentrations exceeded the relevant standard level in the sediment. The risk of combined pollution in the water was relatively low, but high risk was found in the sediments. According to the ISBPSD studies, the survival rates of species in the water and sediments were only 10.0–45.0% and 1.67–11.7% respectively, which was much lower than that reported in other typical basins of China. OCPs, PCMs, and certain metals such as Pb and Ni may be the key toxic pollutants causing biological toxicity effects in Poyang Lake.

Bovine serum albumin and folic acid-modified aurum nanoparticles loaded with paclitaxel and curcumin enhance radiotherapy sensitization for esophageal cancer

Background Nanocarrier systems have been used in the study of esophageal cancer (EC) and other diseases, with significant advantages in improving the non-targeted and nonspecific toxicity of traditional formulations. Some chemotherapeutic drugs and high atomic number nanomaterials have sensitization effects on ionizing radiation and can be used as chemoradiation sensitizers. Methods Aurum (Au) nanoparticles were modified by bovine serum albumin (BSA) and folic acid (FA), and were core-loaded with paclitaxel (PTX) and curcumin (CUR). The basic characteristics of FA-BSA-Au@PTX/CUR nanomedicines were evaluated by transmission electron microscopy, Fourier transform infrared spectroscopy, and Malvern Zetasizer. The encapsulation and release of drugs were monitored by ultraviolet–visible spectrophotometry (UV–Vis). The biological toxicity and radiotherapy sensitization effect of FA-BSA-Au@PTX/CUR were observed by cell viability, colony formation, cell apoptosis, cell cycle distribution, and γ-H2AX analysis experiments. Results The prepared nanomedicines showed good stability and spherical morphology. The results of cell uptake and cell viability detection revealed that FA-BSA-Au@PTX/CUR could specifically target EC cell KYSE150 and exert a certain inhibitory effect on proliferation, with no obvious toxicity on healthy cells Het-1A. In addition, the results of the colony formation experiment, cell apoptosis detection, cell cycle distribution, and γ-H2AX analysis showed that compared with X-rays alone, FA-BSA-Au@PTX/CUR combined with X-rays exhibited relatively stronger radiotherapy sensitization and anti-tumor activity. Conclusions FA-BSA-Au@PTX/CUR could target EC cancer cells and act as a safe and effective radiotherapy sensitizer to improve the radiotherapy efficacy of EC.

Unraveling the mechanism of quercetin alleviating perfluorooctane sulfonate-induced apoptosis in grass carp (Ctenopharyngodon idellus) hepatocytes: AMPK/mTOR-mediated mitophagy

Exposure to persistent new organic pollutants in the environment often leads to high mortality and causes serious economic losses to the aquaculture industry. Currently, perfluorooctane sulfonate (PFOS) is persistent and bio-accumulative in the environment, causing potential risks to aquatic ecosystems, but its toxicity mechanism to aquatic organisms is still unclear. As a natural flavonoid compound, quercetin (QU) has many biological activities such as anti-oxidation, anti-inflammatory, anti-apoptosis and immune regulation. Whether it can be used as a candidate medicine to alleviate PFOS toxicity needs to be further explored. Therefore, in this study, we treated (Ctenopharyngodon idellus) grass carp hepatocytes (L8824) with PFOS (200 μM) and/or QU (60 μM) for 24 h. The results showed that PFOS significantly increased the release of LDH and active oxygen (ROS) in L8824 cells, and led to the decrease of mitochondrial membrane potential (ΔΨm) and ATP content, the increase of mitochondrial ROS, the disorder of mitochondrial dynamics, and the initiation of Bcl-2/Bax-mediated apoptosis. Surprisingly, QU can alleviate the above PFOS-induced grass carp hepatocyte toxicity. In addition, in order to further explore the protective mechanism of QU, we used the molecular docking to predict the binding site between QU and AMPK, and found that there was a high binding capacity between QU and AMPK. In addition, we used Compound C (CC) and 3-Methyladenine (3-MA) to intervene. The results showed that CC and 3-MA intervention aggravated mitochondrial dysfunction and apoptosis factor expression in the QU+PFOS group. These data indicate that PFOS induces oxidative stress, mitochondrial dysfunction, and apoptosis. The regulation of AMPK/mTOR mediated mitophagy by QU may be a new therapeutic strategy to alleviate the hepatotoxicity of PFOS grass carp. This study provides theoretical basis and reference for exploring the toxic mechanism and biological toxic effects of PFOS, and provides a scheme for improving the economic benefits of aquaculture.

1,2-bis(2,4,6-tribromophenoxy) ethane, a novel brominated flame retardant, disrupts intestinal barrier function via the IRX3/NOS2 axis in rat small intestine

Novel brominated flame retardants are widely used in electronics, textiles, furniture, and other products; they can enter the human body through ingestion and respiration and cause harm to the human body, and have been proven to have potential biological toxicity and accumulation effects. 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) is a widely used novel brominated flame retardant; however, there is a lack of research on its mechanism of toxicity, particularly that of intestinal toxicity. Currently, studies on the functionality of iroquois homeobox 3 (IRX3) are extremely limited. In our study, BTBPE was administered to Sprague-Dawley (SD) rats and rat small intestinal crypt epithelial cells (IEC6 cells) in vivo and in vitro, respectively, and hematoxylin and eosin (HE), immunohistochemical, Alcian blue-periodic acid-Schiff (AB-PAS), CCK8, acridine orange/ethidium bromide (AO/EB), fluorescent probes, qPCR, western blotting, and immunofluorescence analyses were performed. To explore the damage mechanism of BTBPE, we used siRNA to silence IRX3 and iNOs-IN-1 (yeast extract-peptone-wheat; YPW) to inhibit nitric oxide synthase 2 (NOS2). The results showed that BTBPE exposure caused inflammation and necroptosis in the jejunum and ileum, as well as destruction of the tight junctions and mucus layer. Moreover, BTBPE activated the IRX3/NOS2 axis both in vivo and in vitro. Silencing IRX3 or inhibiting NOS2 inhibits necroptosis and restores tight junctions in IEC6 cells. In conclusion, our study found that in the jejunum, ileum, and IEC6 cells, BTBPE exposure caused necroptosis and tight junction destruction by activating the IRX3/NOS2 axis. Blocking the IRX3/NOS2 axis can effectively inhibit necroptosis and restore tight junction. In addition, BTBPE exposure caused inflammation and loss of the mucous layer in the jejunum and ileum. Our study is the first to explore the mechanism of intestinal damage caused by BTBPE exposure and to discover new biological functions regulated by the IRX3/NOS2 axis, providing new research directions for necroptosis and tight junctions.

Inhibition of splicing factors SF3A3 and SRSF5 contributes to As3+/Se4+ combination-mediated proliferation suppression and apoptosis induction in acute promyelocytic leukemia cells

The low-dose combination of Arsenite (As3+) and selenite (Se4+) has the advantages of lower biological toxicity and better curative effects for acute promyelocytic leukemia (APL) therapy. However, the underlying mechanisms remain unclear. Here, based on the fact that the combination of 2 μM A3+ plus 4 μM Se4+ possessed a stronger anti-leukemic effect on APL cell line NB4 as compared with each individual, we employed iTRAQ-based quantitative proteomics to identify a total of 58 proteins that were differentially expressed after treatment with As3+/Se4+ combination rather than As3+ or Se4+ alone, the majority of which were involved in spliceosome pathway. Among them, eight proteins stood out by virtue of their splicing function and significant changes. They were validated as being decreased in mRNA and protein levels under As3+/Se4+ combination treatment. Further functional studies showed that only knockdown of two splicing factors, SF3A3 and SRSF5, suppressed the growth of NB4 cells. The reduction of SF3A3 was found to cause G1/S cell cycle arrest, which resulted in proliferation inhibition. Moreover, SRSF5 downregulation induced cell apoptosis through the activation of caspase-3. Taken together, these findings indicate that SF3A3 and SRSF5 function as pro-leukemic factors and can be potential novel therapeutic targets for APL.

Effect of long-term exposure to dyeing wastewater treatment plant effluent on growth and gut microbiota of adult zebrafish (Danio rerio).

Strict standards have been put forward for the treatment and discharge of dyeing wastewater worldwide. However, there are still traces amount of pollutants, especially emerging pollutants in dyeing wastewater treatment plant (DWTP) effluent. Few studies have focused on the chronic biological toxicity effect and mechanism of DWTP effluent. In this study, 3-month chronic compound toxic effects were investigated by the exposure of DWTP effluent using adult zebrafish. Significantly higher mortality and fatness and significantly lower body weight and body length were found in the treatment group. In addition, long-term exposure to DWTP effluent also obviously reduced liver-body weight ratio of zebrafish, causing abnormal liver development of zebrafish. Moreover, DWTP effluent led to obvious changes in the gut microbiota and microbial diversity of zebrafish. At phylum level, significantly higher of Verrucomicrobia but lower Tenericutes, Actinobacteria, and Chloroflexi were found in the control group. At genus level, the treatment group had significantly higher abundance of Lactobacillus, but significantly lower abundance of Akkermansia, Prevotella, Bacteroides, and Sutterella. These results suggested that long-term exposure to DWTP effluent led to imbalance of gut microbiota in zebrafish. In general, this research indicated that DWTP effluent pollutants could result in negative health outcomes to aquatic organisms.

Nanoplastics affect the growth of sea urchins (Strongylocentrotus intermedius) and damage gut health

Nanoplastics (NPs) are abundant and widespread throughout the ocean, not only causing severe environmental pollution, but also worsening the aquatic organisms. To elucidate the mechanism of biological toxic effects underlying the responses of marine invertebrates to NPs, Strongylocentrotus intermedius was stressed with three different NPs concentrations (0 particles/L, 102 particles/L and 104 particles/L). Specific growth rates, enzyme activity, gut tissue section observation and structural characteristics of the gut bacterial community were analyzed. After 28 days of exposure, the specific growth rate of S. intermedius decreased significantly with NPs groups. Further, both lysozyme, pepsin, lipase and amylase activities decreased, while the superoxide dismutase activity increased, indicating that NPs negatively affected digestive enzyme and immune enzyme activity. The analysis of gut tissue sections revealed that NPs caused atrophy and cytoplasmic reduction in the epithelial cells of the S. intermedius intestine. Moreover, the structural characterization of the gut bacterial community indicated significant changes in the abundances of members from Campylobacterota, Chlamydiae, and Firmicutes. Members from Arcobacteraceae, Christensenellaceae and Clostridia were endemic to the NPs treatment. The KEGG database analysis demonstrated that the metabolic pathways specific to the NPs treatment group were significantly associated with growth, energy metabolism, and immunity. In summary, NPs have negatively affected on physiological response and altered gut microecological environment.

Migration, Transformation, and Toxicity of Quaternary Ammonium Antimicrobial Agents in the Environment

Quaternary ammonium compounds (QACs) are one type of widely used cationic biocide, and their usage amount is growing rapidly due to the flu and COVID-19 pandemic. Many QACs were released into the environment in or after the course of their use, and thus they were widely detected in water, sediment, soil, and other environmental media. QACs have stronger surface activity and non-specific biotoxicity, which poses a potential threat to the ecosystem. In this study, the environmental fate and potential toxicity of QACs were documented in terms of their migration and transformation process, biological toxicity effects, and the main mechanisms of bacterial resistance to QACs. Aerobic biodegradation was the main natural way of eliminating QACs in the environment, and the reaction was mainly initiated by the hydroxylation of C atoms at different positions of QACs and finally mineralized to CO2and H2O through decarboxylation, demethylation, and β-oxidation reaction. Toxicological studies showed that QACs at environmental concentrations could not pose acute toxicity to the selected biotas but threatened the growth and reproduction of aquatic organisms like Daphnia magna. Their toxicity effects depended on their molecular structure, the tested species, and the exposed durations. Additionally, our team first investigated the toxicity effects and mechanisms of QACs toward Microcystis aeruginosa, which showed that QACs depressed the algae growth through the denaturation of photosynthetic organelles, suppression of electron transport, and then induction of cell membrane damage. In the environment, the concentrations of QACs were always lower than their bactericidal concentrations, and their degradation could induce the formation of a concentration gradient, which facilitated microbes resistant to QACs. The known resistance mechanisms of bacteria to QACs mainly included the change in cell membrane structure and composition, formation of biofilm, overexpression of the efflux pump gene, and acquisition of resistance genes. Due to the similar targets and mechanisms, QACs could also induce the occurrence of antibiotic resistance, mainly through co-resistance and cross-resistance. Based on the existing data, future research should emphasize the toxicity effect and the potential QACs resistance mechanism of microorganisms in real environmental conditions.

Exposure to high-performance benzotriazole ultraviolet stabilizers: Advance in toxicological effects, environmental behaviors and remediation mechanism using in-silica methods

Benzotriazole ultraviolet stabilizers (BUVSs), as light stabilizers, have attracted widespread attention because of their easy migration in the environment and their acute toxicity and biological toxicity effects, such as immunotoxicity and hepatotoxicity. Accordingly, the treatment and remediation mechanisms of high-performance, environmentally friendly, and low human health risk BUVS substitutes were analyzed. Firstly, the weights and the comprehensive effect (CE) values of migration and toxicity of BUVSs were determined by Topsis assisted by the coefficient of variation (CV) method. From this, a three-dimensional quantitative structure activity relationship (3D-QSAR) model based on the CE values of the 13 BUVSs was constructed. Secondly, EPI software was used to predict the functionality and environmental friendliness of BUVS substitutes, and a partial least squares regression machine learning (ML-PLSR) model was used to analyze the mechanism. Then, ADMET (absorption, distribution, metabolism, excretion, toxicity), TOPKAT, and exposure dose models were used to evaluate the ecological and human health risks of BUVSs and their substitutes. Finally, the key charge information affecting the UV-326 substitutes was deduced by time dependent density functional theory (TDDFT). Using UV-326 as an example, 15 UV-326 substitutes with reduced CE values were designed (reductions of 2.61%–23.18%). Compared with ML-PLSR models of acute toxicity, immunotoxicity, and hepatotoxicity, it was found that the decrease of DM and Qyy values and the increase of Qzz value could further decrease the toxicity of the UV-326 substitutes. Ecological and human health risk assessment showed that the exposure risks of the six UV-326 substitutes were within acceptable limits. TDDFT showed that the change of electron distribution and electron excitation type were the key factors affecting the performance of the UV-326 substitutes, and a charge transfer excitation type was more conducive to obtaining high-performance, environmentally friendly UV-326 substitutes. This study aims to alleviate the toxic damage to the ecological environment and human health caused by BUVS exposure.

Natural medicines of targeted rheumatoid arthritis and its action mechanism.

Rheumatoid arthritis (RA) is an autoimmune disease involving joints, with clinical manifestations of joint inflammation, bone damage and cartilage destruction, joint dysfunction and deformity, and extra-articular organ damage. As an important source of new drug molecules, natural medicines have many advantages, such as a wide range of biological effects and small toxic and side effects. They have become a hot spot for the vast number of researchers to study various diseases and develop therapeutic drugs. In recent years, the research of natural medicines in the treatment of RA has made remarkable achievements. These natural medicines mainly include flavonoids, polyphenols, alkaloids, glycosides and terpenes. Among them, resveratrol, icariin, epigallocatechin-3-gallate, ginsenoside, sinomenine, paeoniflorin, triptolide and paeoniflorin are star natural medicines for the treatment of RA. Its mechanism of treating RA mainly involves these aspects: anti-inflammation, anti-oxidation, immune regulation, pro-apoptosis, inhibition of angiogenesis, inhibition of osteoclastogenesis, inhibition of fibroblast-like synovial cell proliferation, migration and invasion. This review summarizes natural medicines with potential therapeutic effects on RA and briefly discusses their mechanisms of action against RA.

Surface state dominated and carbon core coordinated red-emitting carbon dots for the detection of Cr2O72- and cell imaging

Cr(VI) as a toxic heavy metal ion can easily enter into the body through drinking or eating and cause liver and kidney diseases as well as cancer. Considering its high biological toxicity and adverse effects on human body, it is desirable to develop a probe to monitor its level in the environment. Herein, a high-efficiency fluorescent nanoprobe based on red emissive carbon dots (R-CDs) was established through a convenient solvothermal strategy. The as-prepared CDs with excitation-independency had the fixed emission wavelength at 627 nm when the excitation wavelength was 560 nm. Further study manifested that the new surface state formed by nitrogen and sulfur doping and the increased conjugated system established through dehydration and carbonization were the main reasons for the fluorescence redshift. In this system, these R-CDs as a fluorescent probe exhibited high specificity and sensitivity to Cr2O72- with the linear range of 4–40 μΜ and the limit of detection could reach 80.00 nM. The quenching of these CDs by Cr2O72- was efficiently induced through a static quenching process. Meanwhile, the obtained CDs could enter into HeLa cells through endocytosis and exhibit bright red fluorescence in cells under a confocal laser scanning microscope. Thus, this work provided a promising probe not only for detecting Cr(VI) in natural environment but also for imaging in cells.

β-cyclodextrin/alginate nanoparticles encapsulated 5-fluorouracil as an effective and safe anticancer drug delivery system

Although 5-Fluorouracil (5-FU) is one of the most frequently used cytotoxic chemotherapy drugs in the treatment of cancer, it possesses a short biological half-life and toxic side effects against normal healthy cells. In this work, β-cyclodextrin/alginate (β-CD/Alg) nanoparticles loaded with 5-fluorouracil (5-FU) were prepared to evaluate release properties and bioactivity in different pH media. Stable nanocomposites with the best loading efficiency (36%) and encapsulation efficiency (90%) were successfully fabricated. The size of the nanocomposite solution was determined via dynamic light scattering (DLS) to be in the range 30–120 nm with a mean size of 70 nm, while TEM images showed the particle size of the nanocomposite to be in the range 30–80 nm with a mean size of 50 nm. The release profile of 5-FU in a simulated gastric fluid (pH 1.2) was much lower than in a simulated colorectal fluid (pH 7.4). The release behaviour of 5-FU from the nanocomposite was confirmed by the change in morphology in the pH media. A cytotoxicity assay indicated that the nanocomposite is an effective delivery system for 5-FU with strong antiproliferative activity against MCF-7 cells and negligible effects on normal healthy cells.