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1.
Cancer Innov ; 3(1): e95, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38948536

ABSTRACT

Background: Since RNA sequencing has shown that induced pluripotent stem cells (iPSCs) share a common antigen profile with tumor cells, cancer vaccines that focus on iPSCs have made promising progress in recent years. Previously, we showed that iPSCs derived from leukemic cells of patients with primary T cell acute lymphoblastic leukemia (T-ALL) have a gene expression profile similar to that of T-ALL cell lines. Methods: Mice with T-ALL were treated with dendritic and T (DC-T) cells loaded with intact and complete antigens from T-ALL-derived iPSCs (T-ALL-iPSCs). We evaluated the safety and antitumor efficiency of autologous tumor-derived iPSC antigens by flow cytometry, cytokine release assay, acute toxicity experiments, long-term toxicity experiments, and other methods. Results: Our results indicate that complete tumor antigens from T-ALL-iPSCs could inhibit the growth of inoculated tumors in immunocompromised mice without causing acute and long-term toxicity. Conclusion: T-ALL-iPSC-based treatment is safe and can be used as a potential strategy for leukemia immunotherapy.

2.
Food Res Int ; 190: 114548, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38945593

ABSTRACT

Synthetic preservatives are widely used in the food industry to control spoilage and growth of pathogenic microorganisms, inhibit lipid oxidation processes and extend the shelf life of food. However, synthetic preservatives have some side effects that can lead to poisoning, cancer and other degenerative diseases. With the improvement of living standards, people are developing safer natural preservatives to replace synthetic preservatives, including plant derived preservatives (polyphenols, essential oils, flavonoids), animal derived preservatives (lysozyme, antimicrobial peptide, chitosan) and microorganism derived preservatives (nisin, natamycin, ε-polylysine, phage). These natural preservatives exert antibacterial effects by disrupting microbial cell wall/membrane structures, interfering with DNA/RNA replication and transcription, and affecting protein synthesis and metabolism. This review summarizes the natural bioactive compounds (polyphenols, flavonoids and terpenoids, etc.) in these preservatives, their antioxidant and antibacterial activities, and safety evaluation in various products.


Subject(s)
Antioxidants , Food Preservatives , Food Preservatives/pharmacology , Antioxidants/pharmacology , Anti-Bacterial Agents/pharmacology , Food Preservation/methods , Animals , Food Safety , Humans , Flavonoids/pharmacology , Polyphenols/pharmacology , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Terpenes/pharmacology
3.
Environ Entomol ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38904224

ABSTRACT

Ensuring the safety of insecticides to natural enemy insects of pests is crucial for integrating chemical and biological control strategies. Broflanilide, a novel meta-diamide insecticide, exhibits high insecticidal activity against Myzus persicae (Sulzer) (Hemiptera: Aphididae). To integrate chemical and biological control against M. persicae, we assessed the toxicity of broflanilide to Aphidius gifuensis, and evaluated its safety and sublethal effects. The LC10, LC25, and LC50 values of broflanilide against A. gifuensis were 0.733 mg/L, 1.613 mg/L, and 3.852 mg/L, respectively. The selectivity toxicity ratio of broflanilide to A. gifuensis was 1.516, indicating higher toxicity to M. persicae compared to A. gifuensis. The risk quotient of broflanilide to A. gifuensis adults was 6.18. The percent reduction in the emergence of the parasitoid pupae was -1.15, with a risk grade of 1. The sublethal concentration of broflanilide had no significant influence on the intrinsic rate of increase (r), finite rate of increase (λ), net reproductive rate (R0), and mean fecundity (F) of A. gifuensis in the F1 generation. The mean generation time (T) increased by 0.51 days and 0.39 days in the LC10 and LC25 treatments, respectively; the difference between LC10 treatment and the control was significant, while the difference between LC25 treatment and the control was not significant. The results showed that the sublethal concentration of broflanilide did not have a significant inhibitory effect on the population growth of A. gifuensis.

4.
Sci Rep ; 14(1): 14812, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38926598

ABSTRACT

In recent years, the number of roadway floor rock burst accidents is increasing, which seriously restricts the safe production of the mine. Therefore, safety evaluation method of bottom coal thickness in thick coal seam roadway was studied. The research results shown that the stress concentration area of composite floor is distributed in coal seam or rock stratum with large elastic modulus. With the increase of floor rock strength, the stress of coal-rock composite floor increased gradually, but the displacement and energy decreased gradually. When floor rock strength was equal to bottom coal strength, the increase of floor stress and displacement with the change of bottom coal thickness was the smallest, which was 34.29% and 33.61% respectively. The elastic strain energy decreased from 14.58 to 9.85%. With the increase of bottom coal thickness, the stress and displacement of coal-rock composite floor increased first and then decreased, and the elastic strain energy decreased gradually. It puts forward the safety evaluation method of bottom coal thickness: floor failure depth → reasonable thickness of bottom coal → safety thickness of bottom coal. It can provide reference for design of roadway bottom coal retention and surrounding rock control in thick coal seam face.

5.
JPEN J Parenter Enteral Nutr ; 48(5): 597-604, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38806291

ABSTRACT

BACKGROUND: This study compared the one-time success rate of blind and endoscopy-guided postpyloric feeding tube placement after implementing a comprehensive nursing scheme of intestinal blind placement for patients with ischemic stroke. METHODS: This retrospective cohort study included 179 patients with blind bedside placement and 118 with endoscopy-guided placement. The primary outcome was the one-time success rate of radiologically confirmed postpyloric placement. The secondary endpoints included the position of the tube tip, length of insertion, time of placement, and expenses. The safety endpoints were the incidence of complications caused by placement. RESULTS: The results showed that the method of tube placement did not significantly affect the outcome of the first tube placement (odds ratio [OR] = 0.41; 95% CI = 0.137-1.207; P = 0.105). Compared with endoscopy-guided placement, blind placement was half the cost. We also found that a history of abdominal surgery (OR = 0.003; 95% CI = 0.000-0.059; P < 0.001) and longer intensive care unit (ICU) days (OR = 0.94; 95% CI = 0.903-0.981; P = 0.004) were inversely associated with the one-time success rate. CONCLUSION: Our study suggested that blind intestinal feeding tube placement has an equivalent one-time success rate compared with endoscopy-guided placement in hospitalized patients with ischemic stroke if operators can be trained well. However, the expenses of endoscopy-guided placement were twice those of blind bedside methods. We also found that patients with abdominal surgery history and longer ICU stay were more likely to fail at the first placement. Further research is needed to replicate our single-center observations in a larger population of patients.


Subject(s)
Enteral Nutrition , Intubation, Gastrointestinal , Ischemic Stroke , Humans , Retrospective Studies , Enteral Nutrition/methods , Male , Female , Intubation, Gastrointestinal/methods , Aged , Middle Aged , Intensive Care Units , Treatment Outcome , Length of Stay/statistics & numerical data
6.
Ultrason Sonochem ; 107: 106892, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38761772

ABSTRACT

Litsea cubeba essential oil (LCEO) has garnered widespread attention due to its robust biological activity. However, challenges such as high volatility, limited water solubility, and low bioavailability impede its application. Nano-emulsion encapsulation technology offers an effective solution to these issues. In this study, we prepared litsea cubeba essential oil nano-emulsion (LCEO-NE) for the first time using whey protein (WP) as the emulsifier through an ultrasonic-assisted method, achieving high efficiency with minimal energy consumption. Transmission electron microscopy and dynamic light scattering analyses revealed that the nanoparticles were uniformly spherical, with a particle size of 183.5 ± 1.19 nm and a zeta potential of -35.5 ± 0.95 mV. Stability studies revealed that LCEO-NE exhibited excellent thermal and salt stability, maintaining its integrity for up to four weeks when stored at 4 °C and 25 °C. In vitro digestion assays confirmed the digestibility of LCEO-NE. Furthermore, evaluation of the DPPH, ABTS, and antimicrobial activities revealed that LCEO-NE displayed superior bacteriostatic and antioxidant properties compared to LCEO. Scanning electron microscopy elucidated that its bacteriostatic effect involved the disruption of bacterial microstructure. Hemocompatibility and cytotoxicity assays demonstrated the safety of LCEO-NE within the effective concentration range. This research supports the utilization of nanoparticles for encapsulating LCEO, thereby enhancing its stability and bioactivity, and consequently expanding its applications in the food and pharmaceutical industries.


Subject(s)
Emulsions , Litsea , Oils, Volatile , Whey Proteins , Litsea/chemistry , Whey Proteins/chemistry , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/toxicity , Antioxidants/pharmacology , Antioxidants/chemistry , Sonication , Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Particle Size , Drug Stability , Humans
7.
Environ Pollut ; 352: 124082, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38697246

ABSTRACT

Antimony (Sb) contamination in certain areas caused by activities such as antimony mining and smelting poses significant risks to human health and ecosystems. In this study, a stable composite material consisting of natural zeolite-supported nanoscale zero-valent iron (Z-ZVI) was successfully prepared. The immobilization effect of Z-ZVI on Sb in contaminated soil was investigated. Experimental results showed that Z-ZVI exhibited superior performance compared to pure nano zero-valent iron (nZVI) in terms of stability, with a lower zeta potential (-25.16 mV) at a pH of 7 and a higher specific surface area (54.54 m2/g). It can be easily applied and dispersed in contaminated soils. Additionally, Z-ZVI demonstrated a more abundant porous structure. After 60 days of treatment with 3% Z-ZVI, the leaching concentration of Sb in the contaminated soil decreased from 1.32 mg/L to 0.31 mg/L (a reduction of 76%), and the concentration of available Sb species decreased from 19.84 mg/kg to 0.71 mg/kg, achieving a fixation efficiency of up to 90%. X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) analysis confirmed the effective immobilization of Sb in the soil through reduction of antimonate to antimonite, precipitation, and adsorption processes facilitated by Z-ZVI. Moreover, the addition of Z-ZVI effectively reduced the bioavailability of Sb in the contaminated soil, thereby mitigating its toxicity to earthworms. In conclusion, Z-ZVI can be utilized as a promising material for the safe remediation and antimony and other heavy metal-contaminated soils.


Subject(s)
Antimony , Iron , Soil Pollutants , Soil , Zeolites , Antimony/chemistry , Soil Pollutants/chemistry , Zeolites/chemistry , Iron/chemistry , Soil/chemistry , Environmental Restoration and Remediation/methods , Adsorption , Animals
8.
Front Pharmacol ; 15: 1389293, 2024.
Article in English | MEDLINE | ID: mdl-38783954

ABSTRACT

Halicin, the first antibacterial agent discovered by artificial intelligence, exerts broad-spectrum antibacterial effects and has a unique structure. Our study found that halicin had a good inhibitory effect on clinical isolates of drug-resistant strains and Clostridium perfringens (C. perfringens). The safety of halicin was evaluated by acute oral toxicity, genotoxicity and subchronic toxicity studies. The results of acute toxicity test indicated that halicin, as a low-toxicity compound, had an LD50 of 2018.3 mg/kg. The results of sperm malformation, bone marrow chromosome aberration and cell micronucleus tests showed that halicin had no obvious genotoxicity. However, the results of the 90-day subchronic toxicity test indicated that the test rats exhibited weight loss and slight renal inflammation at a high dose of 201.8 mg/kg. Teratogenicity of zebrafish embryos showed that halicin had no significant teratogenicity. Analysis of intestinal microbiota showed that halicin had a significant effect on the intestinal microbial composition, but caused a faster recovery. Furthermore, drug metabolism experiments showed that halicin was poorly absorbed and quickly eliminated in vivo. Our study found that halicin had a good therapeutic effect on intestinal infection model of C. perfringens. These results show the feasibility of developing oral halicin as a clinical candidate drug for treating intestinal infections.

9.
Waste Manag ; 183: 174-183, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38759275

ABSTRACT

Solid-phase residues from pyrolysis of oily wastes (OS) are widely used due to their rich pore structure and strong adsorption capacity. In this study, pyrolysis residues (OS-P) were obtained from the pyrolysis treatment of four typical OS in Karamay, Xinjiang. The results indicate that the crystalline substances in OS-P mainly were SiO2, BaSO4, and graphite. The heavy metals of OS-P were higher than that of OS in the following order: Zn > Cu > Ni > Cr > Pb > Cd. The results of the improvement of Community Bureau of Reference (BCR) sequential extraction showed that the proportion of Cu, Ni and Cr in OS1-P in the residual fraction was higher than that of the other three OS. The residual fraction of Cu, Ni, and Cr in OS1-P increased from 16.0 %, 30.0 %, and 11.0 % to 66.1 %, 81.9 %, and 89.2 %, respectively. After pyrolysis treatment, the leaching concentration of heavy metals in the residue was reduced. Referring to the requirements for heavy metal control limits (GB 4284-2018), all heavy metals in OS-P showed low risk. Their potential ecological risk indices were 4.11, 3.13, 4.87 and 5.35, respectively, indicating that the potential ecological hazards of heavy metals from OS-P were slight. There was no significant effect on the histopathological changes of kidney, lung, liver, ovary and testis of mice, showing that the rational use of OS-P in production will not produce toxic effects on target animals. Based on risk assessment and safety evaluation, the application of OS-P is controllable, safe and reliable for resource utilization.


Subject(s)
Metals, Heavy , Pyrolysis , Metals, Heavy/analysis , Risk Assessment/methods , Animals , Mice , China , Refuse Disposal/methods
10.
Fish Shellfish Immunol ; 150: 109569, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38641216

ABSTRACT

Phlorotannins are phenolic compounds with diverse biological activities, yet their efficacy in aquatic animals currently remains unclear. This investigation scrutinized the influence of phlorotannins on the growth, immunity, antioxidant capacity, and intestinal microbiota in Litopenaeus vannamei, concurrently evaluating the potential adverse effects of phlorotannins on L. vannamei. A base diet without phlorotannins supplementation was used as a control, and 4 groups of diets with different concentrations (0, 0.5, 1.0, 2.0 g kg-1) of phlorotannins were formulated and fed to juvenile shrimp (0.25 ± 0.01 g) for 60 days followed by a 24-h challenge with Vibrio parahaemolyticus with triplicate in each group. Compared with the control, dietary 2.0 g kg-1 phlorotannins significantly improved the growth of the shrimp. The activities of enzymes related to cellular immunity, humoral immunity, and antioxidants, along with a notable upregulation in the expression of related genes, significantly increased. After V. parahaemolyticus challenge, the cumulative survival rates of the shrimp demonstrated a positive correlation with elevated concentrations of phlorotannins. In addition, the abundance of Bacteroidetes and functional genes associated with metabolism increased in phlorotannins supplementation groups. Phlorotannins did not elicit any detrimental effects on the biological macromolecules or histological integrity of the hepatopancreas or intestines. Simultaneously, it led to a significant reduction in malondialdehyde content. All results indicated that phlorotannins at concentrations of 2.0 g kg-1 can be used as safe feed additives to promote the growth, stimulate the immune response, improve the antioxidant capacity and intestinal health of L. vannamei, and an protect shrimp from damage caused by oxidative stress.


Subject(s)
Animal Feed , Diet , Dietary Supplements , Gastrointestinal Microbiome , Penaeidae , Tannins , Vibrio parahaemolyticus , Animals , Penaeidae/immunology , Penaeidae/growth & development , Penaeidae/drug effects , Penaeidae/microbiology , Animal Feed/analysis , Diet/veterinary , Gastrointestinal Microbiome/drug effects , Tannins/pharmacology , Tannins/administration & dosage , Vibrio parahaemolyticus/physiology , Dietary Supplements/analysis , Dose-Response Relationship, Drug , Random Allocation , Immunity, Innate/drug effects
11.
Toxicol In Vitro ; 98: 105816, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38604524

ABSTRACT

Skin corrosion testing is integral to evaluating the potential harm posed by chemicals, impacting regulatory decisions on safety, transportation, and labeling. Traditional animal testing methods are giving way to in vitro alternatives, such as reconstructed human epidermis (RhE) models, aligning with evolving ethical standards. This study evaluates the QileX-RhE test system's performance for chemical subcategorization within the OECD TG 431 framework. Results demonstrate its ability to differentiate subcategories, accurately predicting 83% of UN GHS Category 1A and 73% of UN GHS Category 1B/1C chemicals with 100% sensitivity in corrosive prediction. Additionally, this study provides a comprehensive assessment of the test method's performance by employing nuanced parameters such as positive predictive value (PPV), negative predictive value (NPV), post-test odds and likelihood rations, offering valuable insights into the applicability and effectiveness of the QileX-RhE test method.


Subject(s)
Animal Testing Alternatives , Organisation for Economic Co-Operation and Development , Humans , Skin Irritancy Tests/methods , Caustics/toxicity , Epidermis/drug effects
12.
Altern Lab Anim ; 52(3): 166-176, 2024 May.
Article in English | MEDLINE | ID: mdl-38626463

ABSTRACT

The Korean Center for the Validation of Alternative Methods (KoCVAM), which promotes the Three Rs principles and the use of alternative methods in Korea, has been operating within the Toxicological Screening and Testing Division of the Ministry of Food and Drug Safety (MFDS) since 2009. KoCVAM has exchanged opinions and information on the development and validation of non-animal alternative test methods as part of the International Cooperation on Alternative Test Methods (ICATM), and provided input into draft OECD Test Guidelines (TGs). Several Korean laws (e.g. the Cosmetics Act) encourage the use of alternative test methods for chemical testing and assessment. To promote and support the use of alternative test methods in the country, KoCVAM has published information and provided training on the national guidelines, which are based on the OECD TGs. In addition, KoCVAM has held annual training workshops on alternative test methods, to help Korean research institutions (including GLP test facilities) to implement them. In addition, by helping to develop and validate alternative test methods that were adopted in OECD TG 442B, TG 492 and TG 439, KoCVAM has contributed to the enhanced competitiveness of Korean industry on the worldwide stage.


Subject(s)
Animal Testing Alternatives , Republic of Korea , Animal Testing Alternatives/methods , Animals , Guidelines as Topic
13.
Int J Mol Sci ; 25(8)2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38674100

ABSTRACT

The accurate prediction of adverse drug reactions (ADRs) is essential for comprehensive drug safety evaluation. Pre-trained deep chemical language models have emerged as powerful tools capable of automatically learning molecular structural features from large-scale datasets, showing promising capabilities for the downstream prediction of molecular properties. However, the performance of pre-trained chemical language models in predicting ADRs, especially idiosyncratic ADRs induced by marketed drugs, remains largely unexplored. In this study, we propose MoLFormer-XL, a pre-trained model for encoding molecular features from canonical SMILES, in conjunction with a CNN-based model to predict drug-induced QT interval prolongation (DIQT), drug-induced teratogenicity (DIT), and drug-induced rhabdomyolysis (DIR). Our results demonstrate that the proposed model outperforms conventional models applied in previous studies for predicting DIQT, DIT, and DIR. Notably, an analysis of the learned linear attention maps highlights amines, alcohol, ethers, and aromatic halogen compounds as strongly associated with the three types of ADRs. These findings hold promise for enhancing drug discovery pipelines and reducing the drug attrition rate due to safety concerns.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Humans , Deep Learning , Models, Chemical , Rhabdomyolysis/chemically induced , Long QT Syndrome/chemically induced
14.
BMC Proc ; 18(Suppl 7): 7, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38658942

ABSTRACT

Complex perianal fistula is a common complication of Crohn's disease (CD) which leads to negative impact on patient's quality of life. Successful management of the disease requires a multidisciplinary approach, including a gastroenterologist and a colorectal surgeon, applying combined surgical and medical therapy. One of frequently practiced surgical procedures is seton placement in the fistula tract, which is used to control perianal sepsis and drain the fistula, while preventing recurrent abscess formation.Darvadstrocel, a suspension of expanded, allogeneic, adipose-derived, mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Following approval of darvadstrocel, the INSPIRE registry is being conducted in order to evaluate long-term safety and effectiveness of the drug on a large, heterogenous population.An online expert meeting was held from March 20 to March 30, 2023, which provided relevant insights into the decision-making process regarding seton use and obtained feedback on the first experiences with darvadstrocel. The aim of this article is to present the perspectives from gastroenterologists and colorectal surgeons practicing in Czechia, Hungary, Israel, Lithuania, Serbia, and Slovenia in topics such as diagnosis and treatment options for patients with complex Crohn's perianal fistulas (CPF), specifically focusing on the use of setons and darvadstrocel.During this virtual session, unavailability of comprehensive data on safety and efficacy of available treatment procedures was emphasized as an important obstacle towards development of standardized recommendations and improvement of outcomes in treatment of (CPF). Furthermore, achieving consensus in seton use, duration of its placement, and frequency of change is recognized as one of CPF treatments major challenges. Despite these issues, it is important to promote better understanding and treatment of complex perianal fistulas in order to improve the quality of life of those affected by this condition.

15.
Zygote ; 32(2): 175-182, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38629180

ABSTRACT

Intracytoplasmic sperm injection (ICSI) is a technique that directly injects a single sperm into the cytoplasm of mature oocytes. Here, we explored the safety of single-sperm cryopreservation applied in ICSI. This retrospective study enrolled 186 couples undergoing ICSI-assisted pregnancy. Subjects were allocated to the fresh sperm (group A)/single-sperm cryopreservation (group B) groups based on sperm type, with their clinical baseline/pathological data documented. We used ICSI-compliant sperm for subsequent in vitro fertilization and followed up on all subjects. The recovery rate/cryosurvival rate/sperm motility of both groups, the pregnancy/outcome of women receiving embryo transfer, and the delivery mode/neonatal-related information of women with successful deliveries were recorded. The clinical pregnancy rate, cumulative clinical pregnancy rate, abortion rate, ectopic pregnancy rate, premature delivery rate, live birth delivery rate, neonatal birth defect rate, and average birth weight were analyzed. The two groups showed no significant differences in age, body mass index, ovulation induction regimen, sex hormone [anti-Müllerian hormone (AMH)/follicle-stimulating hormone (FSH)/luteinizing hormone (LH)] levels, or oocyte retrieval cycles. The sperm recovery rate (51.72%-100.00%) and resuscitation rate (62.09% ± 16.67%) in group B were higher; the sperm motility in the two groups demonstrated no significant difference and met the ICSI requirements. Group B exhibited an increased fertilization rate, decreased abortion rate, and increased safety versus group A. Compared with fresh sperm, the application of single-sperm cryopreservation in ICSI sensibly improved the fertilization rate and reduced the abortion rate, showing higher safety.


Subject(s)
Cryopreservation , Pregnancy Rate , Sperm Injections, Intracytoplasmic , Sperm Motility , Spermatozoa , Humans , Sperm Injections, Intracytoplasmic/methods , Female , Cryopreservation/methods , Male , Pregnancy , Adult , Retrospective Studies , Spermatozoa/physiology , Semen Preservation/methods , Pregnancy Outcome , Embryo Transfer/methods , Fertilization in Vitro/methods
16.
Toxicol Res (Camb) ; 13(2): tfae057, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38623091

ABSTRACT

Objective: The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), called Atractylodes macrocephala rhizome (AMR) and known by its traditional name Bai Zhu, is a prominent Chinese herbal medicine employed for preventing miscarriage. However, our previous study revealed that high dosages of AMR administered during pregnancy could cause embryotoxicity but the specific embryotoxic components and their underlying mechanisms remain unclear. This study aimed to screen and identify the potential embryotoxic components of AMR. Methods: The AMR extracts and sub-fractions were analyzed by thin layer chromatography and subsequently screened by in vitro mouse limb bud micromass and mouse whole embryo culture bioassays. The embryotoxic fractions from AMR were further evaluated in vivo using a pregnant mouse model. The structures of the potential embryotoxic components were analyzed using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Results: In vitro and in vivo bioassays revealed that AMR glycoside-enriched sub-fractions (AMR-A-IIa and AMR-A-IIb) exhibited potential embryotoxicity. These sub-fractions, when administered to pregnant animals, increased the incidence of stillbirth and congenital limb malformations. MS spectrometry analysis identified cycasin derivatives in both sub-fractions, suggesting their possible role in the observed limb malformations. However, further experiments are necessary to validate this hypothesis and to elucidate the underlying mechanisms. Conclusions: Our study provides significant scientific evidence on the pharmacotoxicity of AMR, which is important for the safe clinical application of commonly used Chinese herbal medicines during pregnancy.

17.
Article in English | MEDLINE | ID: mdl-38656721

ABSTRACT

At present, understanding of neonicotinoid toxicity in arthropods remains limited. We here evaluated the lethal and sublethal effects of acetamiprid in F0 and F1 generations of Binodoxys communis using a range of sublethal concentrations. The 10% lethal concentration (LC10) and half lethal concentration (LC25) of ACE had negative effects on the B. communis survival rate, adult longevity, parasitism rate, and emergence rate, and significantly prolonged the duration of the developmental cycle. ACE also had intergenerational effects, with some biological indices affected in the F1 generation after pesticide exposure. Transcriptomic analysis demonstrated that differentially expressed genes were enriched in specific pathways including the amino acid metabolism, carbohydrate metabolism, energy metabolism, exogenous metabolism, signal transduction, and glutathione metabolism pathways. These results indicated strong contact toxicity of ACE to B. communis, which may inhibit their biological control capacity. These results improve our understanding of the toxicological mechanisms of parasitic natural enemies in response to insecticide exposure.

18.
J Cancer ; 15(7): 2024-2032, 2024.
Article in English | MEDLINE | ID: mdl-38434976

ABSTRACT

Objective: This study evaluated the efficacy and safety of the gemcitabine and oxaliplatin intrathoracic perfusion chemotherapy (IPCGOR) regimen combined with interleukin-2 (IL-2) for advanced non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of 460 advanced NSCLC patients from the Yunnan Province Early Cancer Diagnosis and Treatment Project (June 2020-October 2022), assessing the IPCGOR and IL-2 combination. Outcomes were measured based on RECIST 1.1 criteria, focusing on objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (MOS), and treatment safety. Results: The treatment demonstrated an ORR of 67.4%, a DCR of 97.4%, an mPFS of 8.5 months, and an MOS of 12.5 months. 14 patients underwent successful surgery post-treatment. Common adverse reactions were manageable, with no treatment-related deaths reported. Conclusion: The IPCGOR combined with IL-2 regimen shows promising efficacy and a tolerable safety profile for advanced NSCLC. These findings suggest its potential as a reference for treating advanced NSCLC. However, the study's retrospective nature and single-center design pose limitations. Future research should focus on prospective studies, randomized controlled trials, and long-term outcome assessments, particularly in diverse patient subgroups, to further validate and refine the clinical application of this regimen.

19.
Article in English | MEDLINE | ID: mdl-38430332

ABSTRACT

Levilactobacillus brevis KU15006, isolated from kimchi, exhibits pathogen-antagonistic and anti-diabetic activities; however, the safety of this strain has not been assessed. In the present study, L. brevis KU15006 was evaluated to elucidate its safety as a probiotic strain using phenotypic and genotypic analyses. Its safety was assessed using a minimum inhibitory concentration test comprising nine antibiotics, 26 antibiotic resistance genes, a single conjugative element, virulence gene analysis, hemolysis, cell cytotoxicity, mucin degradation, and toxic metabolite production. L. brevis KU15006 exhibited equal or lower minimum inhibitory concentration for the nine antibiotics than the cut-off value established by the European Food Safety Authority. It did not harbor antibiotic resistance and virulence genes. L. brevis KU15006 lacked ß-hemolysis, mucin degradation, cytotoxicity against Caco-2 cells, gelatin liquefaction, bile salt deconjugation, and toxic metabolite production abilities. Based on the results, L. brevis KU15006, which has antagonistic and anti-diabetic effects, could be marketed as a probiotic in the future.

20.
Accid Anal Prev ; 199: 107530, 2024 May.
Article in English | MEDLINE | ID: mdl-38437756

ABSTRACT

Merging areas serve as the potential bottlenecks for continuous traffic flow on freeways. Traffic incidents in freeway merging areas are closely related to decision-making errors of human drivers, for which the autonomous vehicles (AVs) technologies are expected to help enhance the safety performance. However, evaluating the safety impact of AVs is challenging in practice due to the lack of real-world driving and incident data. Despite the increasing number of simulation-based AV studies, most relied on single traffic/vehicle driving simulators, which exhibit limitations such as inaccurate description of AV behavior using pre-defined driving models, limited testing modules, and a lack of high-fidelity traffic scenarios. To this end, this study addresses these challenges by customizing different types of car-following models for AVs on freeway and developing a software-in-the-loop co-simulation platform for safety performance evaluation. Specifically, the environmental perception module is integrated in PreScan, the decision-making and control model for AVs is designed by Matlab, and the traffic flow environment is established by Vissim. Such a co-simulation platform is supposed to be able to reproduce the mixed traffic with AVs to a large extent. By taking a real freeway merging scenario as an example, comprehensive experiments were conducted by introducing a single AV and multiple AVs on the mainline of freeway, respectively. The single AV experiment investigated the performance of different car-following models microscopically in the case of merging conflict. The safety and comfort of AVs were examined in terms of TTC and jerk, respectively. The multiple AVs experiment examined the safety impact of AVs on mixed traffic of freeway merging areas macroscopically using the developed risk assessment model. The results show that AVs could bring significant benefits to freeway safety, as traffic conflicts and risks are substantially reduced with incremental market penetration rates.


Subject(s)
Autonomous Vehicles , Humans , Accidents, Traffic/prevention & control , Computer Simulation , Software
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