Bifenthrin induces changes in clinical poisoning symptoms, oxidative stress, DNA damage, histological characteristics, and transcriptome in Chinese giant salamander (Andrias davidianus) larvae.

Bifenthrin (BF) is a broad-spectrum insecticide that has gained widespread use due to its high effectiveness. However, there is limited research on the potential toxic effects of bifenthrin pollution on amphibians. This study aimed to investigate the 50 % lethal concentration (LC50) and safety concentration of Chinese giant salamanders (CGS) exposed to BF (at 0, 6.25,12.5,25 and 50 µg/L BF) for 96 h. Subsequently, CGS were exposed to BF (at 0, 0.04, and 4 µg/L BF) for one week to investigate its toxic effects. Clinical poisoning symptoms, liver pathology, oxidative stress factors, DNA damage, and transcriptome differences were observed and analyzed. The results indicate that exposure to BF at 4 µg/L significantly decreased the adenosine-triphosphate (ATP), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) contents in the brain, liver, and kidney of CGS. Additionally, the study found that the malondialdehyde (MDA), reactive oxygen species (ROS), and 8-hydroxydeoxyguanosine (8-OHdG) contents were increased. The liver tissue exhibited significant inflammatory reactions and structural malformations. RNA-seq analysis of the liver showed that BF caused abnormal antioxidant indices of CGS. This affected molecular function genes such as catalytic activity, ATP-dependent activity, metabolic processes, signaling and immune system processes, behavior, and detoxification, which were significantly upregulated, resulting in the differential genes significantly enriched in the calcium signaling pathway, PPARα signaling pathway and NF-kB signaling pathway. The results suggest that BF induces the abnormal production of free radicals, which overwhelms the body's self-defense system, leading to varying degrees of oxidative stress. This can result in oxidative damage, DNA damage, abnormal lipid metabolism, autoimmune diseases, clinical poisoning symptoms, and tissue inflammation. This work provides a theoretical basis for the rational application of bifenthrin and environmental risk assessment, as well as scientific guidance for the conservation of amphibian populations.

Degradation of 2, 4-dichlorophenol by peroxymonosulfate catalyzed by ZnO/ZnMn2 O4.

In this study, a highly efficient peroxymonosulfate (PMS) activator, ZnO/ZnMn2 O4 , was synthesized using a simple one-step hydrothermal method. The resulting bimetallic oxide catalyst demonstrated a homogenous and high-purity composition, showcasing synergistic catalytic activity in activating PMS for degrading 2, 4-dichlorophenol (2, 4-DCP) in aqueous solution. This catalytic performance surpassed that of individual ZnO, Mn2 O3 , and ZnMn2 O4 metal materials. Under the optimized conditions, the removal efficiency of 2, 4-DCP reached approximately 86% within 60 min, and the catalytic ability remained almost constant even after four cycles of recycling. The developed degradation system proved effective in degrading other azo-dye pollutants. Certain inorganic anions such as HPO4 - , HCO3 - , and NO3 - significantly inhibited the degradation of 2, 4-DCP, while Cl- and SO4 2- did not exhibit such interference. Results from electrochemical experiments indicated that the electron transfer ability of ZnO/ZnMn2 O4 surpassed that of individual metals, and electron transfer occurred between ZnO/ZnMn2 O4 and the oxidant. The primary active radicals responsible for degrading 2, 4-DCP were identified as SO4 •- , OH• and O2 •- , generated through the oxidation and reduction of PMS catalyzed by Zn (II) and Mn (III). Furthermore, X-ray photoelectron spectroscopy (XPS) analysis of the fresh and used catalysts revealed that the exceptional electron transfer ability of ZnO facilitated the valence transfer of Mn (III) and the transfer of electrons to the catalyst's oxygen surface, thus enhancing the catalytic efficiency. The analysis of radicals and intermediates indicates that the two main pathways for degrading 2, 4-DCP involve hydroxylation and radical attack on its aromatic ring. PRACTITIONER POINTS: A bimetallic ZnO/ZnMn2 O4 catalyst was synthesized and characterized. ZnO/ZnMn2 O4 can synergistically activate PMS to degrade 2, 4-DCP compared with single metal oxide. Three primary active radicals, O2 •- , • OH, and SO4 •- , were generated to promote the degradation. ZnO promoted electron transfer among the three species of Mn to facilitate oxidizing pollutants. Hydroxylation and radical attack on the aromatic ring of 2, 4-DCP are the two degradation pathways.

Evaluation of Chelator-to-Antibody Ratio on Development of 89Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor.

89Zr-iPET has been widely used for preclinical and clinical immunotherapy studies to predict patient stratification or evaluate therapeutic efficacy. In this study, we prepared and evaluated 89Zr-DFO-anti-PD-L1-mAb tracers with varying chelator-to-antibody ratios (CARs), including 89Zr-DFO-anti-PD-L1-mAb_3X (tracer_3X), 89Zr-DFO-anti-PD-L1-mAb_10X (tracer_10X), and 89Zr-DFO-anti-PD-L1-mAb_20X (tracer_20X). The DFO-anti-PD-L1-mAb conjugates with varying CARs were prepared using a random conjugation method and then subjected to quality control. The conjugates were radiolabeled with 89Zr and evaluated in a PD-L1-expressing CT26 tumor-bearing mouse model. Next, iPET imaging, biodistribution, pharmacokinetics, and ex vivo pathological and immunohistochemical examinations were conducted. LC-MS analysis revealed that DFO-anti-PD-L1-mAb conjugates were prepared with CARs ranging from 0.4 to 2.0. Radiochemical purity for all tracer groups was >99% after purification. The specific activity levels of tracer_3X, tracer_10X, and tracer_20X were 2.2 ± 0.6, 8.2 ± 0.6, and 10.5 ± 1.6 µCi/µg, respectively. 89Zr-iPET imaging showed evident tumor uptake in all tracer groups and reached the maximum uptake value at 24 h postinjection (p.i.). Biodistribution data at 168 h p.i. revealed that the tumor-to-liver, tumor-to-muscle, and tumor-to-blood uptake ratios for tracer_3X, tracer_10X, and tracer_20X were 0.46 ± 0.14, 0.58 ± 0.33, and 1.54 ± 0.51; 4.7 ± 1.3, 7.1 ± 3.9, and 14.7 ± 1.1; and 13.1 ± 5.8, 19.4 ± 13.8, and 41.3 ± 10.6, respectively. Significant differences were observed between tracer_3X and tracer_20X in the aforementioned uptake ratios at 168 h p.i. The mean residence time and elimination half-life for tracer_3X, tracer_10X, and tracer_20X were 25.4 ± 4.9, 24.2 ± 6.1, and 25.8 ± 3.3 h and 11.8 ± 0.5, 11.1 ± 0.7, and 11.7 ± 0.6 h, respectively. No statistical differences were found between-tracer in the aforementioned pharmacokinetic parameters. In conclusion, 89Zr-DFO-anti-PD-L1-mAb tracers with a CAR of 1.4-2.0 may be better at imaging PD-L1 expression in tumors than are traditional low-CAR 89Zr-iPET tracers.

Study on the catalytic degradation of Acid Orange 7 and the potential mechanism by ferrous-percarbonate.

Factors affecting the degradation of Acid Orange 7 (AO7) were evaluated and optimized when ferrous was used to catalyze percarbonate in the present study. The optimized conditions included the initial pH values ranging from 3 to 11 for AO7 solution, the initial level of AO7, sodium percarbonate (SPC), and Fe2+ . Some ions and natural organic materials, which commonly exist in natural water, were also tested to evaluate their potential impacts on the degradation of AO7. The degradation efficiency of AO7 was up to 95% under the optimized test conditions, where the ferrous/percarbonate/AO7 molar ratio was 15/10/1 in the 0.285 mmol/l AO7 aqueous solution. The presence of Cl- , SO4 2- , NO3 - , Na+ , and Mg2+ did not affect the removal of AO7. The addition of HCO3 - significantly inhibited its removal, even when the concentration of HCO3 - was low to 0.6 mmol/l. A slight inhibition effect was observed when the added concentration of humic acid ranged from 0.5 to 5 mg/l, whereas the residue of AO7 was significantly enhanced when the level of humic acid was continually increased from 50 to 100 mg/l. Hydroxyl radicals (•OH) were the main reactive intermediates controlling the oxidation of AO7 in the present Fe2+ /SPC system. The produced intermediates through the degradation of AO7 were identified to include 2-coumaranone, 2-naphthol, phthalic acid, phthalimide, N-methylnaphthylamine, and 2-methylphenol. The proposed degradation pathways are consistent with the radical formation and the identified intermediates. PRACTITIONER POINTS: The ferrous/percarbonate system can remove 95% of AO7 under the optimized conditions. AO7 removal was inhibited by adding HCO3 - and humic acid, but not affected by Cl- , SO4 2- , NO3 - , Na+ , and Mg2+ . Hydroxylation, ring opening, and mineralization driven by the generated hydroxyl radicals were derived as the major processes for degrading AO7.

Comparison of BMIPP-SPECT/CT to 18FDG-PET/CT for Imaging Brown or Browning Fat in a Preclinical Model.

Obesity is a leading cause of preventable death and morbidity. To elucidate the mechanisms connecting metabolically active brown adipose tissue (BAT) and metabolic health may provide insights into methods of treatment for obesity-related conditions. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) is traditionally used to image human BAT activity. However, the primary energy source of BAT is derived from intracellular fatty acids and not glucose. Beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) is a fatty acid analogue amenable to in vivo imaging by single photon emission computed tomography/CT (SPECT/CT) when radiolabeled with iodine isotopes. In this study, we compare the use of 18FDG-PET/CT and 125I-BMIPP-SPECT/CT for fat imaging to ascertain whether BMIPP is a more robust candidate for the non-invasive evaluation of metabolically active adipose depots. Interscapular BAT, inguinal white adipose tissue (iWAT), and gonadal white adipose tissue (gWAT) uptake of 18FDG and 125I-BMIPP was quantified in mice following treatment with the BAT-stimulating drug CL-316,243 or saline vehicle control. After CL-316,243 treatment, uptake of both radiotracers increased in BAT and iWAT. The standard uptake value (SUVmean) for 18FDG and 125I-BMIPP significantly correlated in these depots, although uptake of 125I-BMIPP in BAT and iWAT more closely mimicked the fold-change in metabolic rate as measured by an extracellular flux analyzer. Herein, we find that imaging BAT with the radioiodinated fatty acid analogue BMIPP yields more physiologically relevant data than 18FDG-PET/CT, and its conventional use may be a pivotal tool for evaluating BAT in both mice and humans.

Radiation Dose Due to Naturally Occurring Radionuclides in Soils from Varying Geological Environments.

Field radiation monitoring and radionuclide analysis of soils were performed at various geological areas in Taiwan. The field-observed dose rate was 0.031-0.107 µGy h. The dose rate ascribed to naturally occurring radionuclides in soils that were geologically characterized varied from 0.002 to 0.079 µGy h. A linear correlation was observed between the activity-derived and field-observed dose, which indicated that the absorbed dose rate from the cosmic rays is almost constant (0.030 µGy h) throughout the flat area on the island.

Evaluation of Injectable Chitosan-based Co-cross-linking Hydrogel for Local Delivery of 188Re-LIPO-DOX to Breast-tumor-bearing Mouse Model.

BACKGROUND/AIM: An injectable chitosan-based co-cross-linking thermosensitive hydrogel combining 188Re- and doxorubicin-encapsulated liposomes (C/GP/GE/188Re-LIPO-DOX) was developed for the prevention of locoregional recurrence after mastectomy. MATERIALS AND METHODS: The hydrogel properties, in vitro drug release characteristics, and in vivo scintigraphy imaging attributes were investigated. RESULTS: The gelation time of the hydrogels can be controlled to be within 5 min. Results from Fourier-transform infrared spectroscopy, scanning electron microscopy, and dynamic mechanical analysis showed that a covalent cross-linking reaction between chitosan and genipin occurred and that the hydrogel's mechanical strength and chemical stability were improved. In vitro drug release studies showed that the hydrogel can prolong the release of doxorubicin by several weeks (51.5%±5.3% at 21 days). In addition, in vivo scintigraphy results suggested high retention rates (43.1%±1.0% at 48 h) of the radiopharmaceutical compound at the tumor injection site. CONCLUSION: The preliminary results indicated that the C/GP/GE/188Re-LIPO-DOX radiopharmaceutical hydrogel is a potential candidate for further in vivo therapeutic evaluation.

Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model.

PURPOSE: In this study, the (188)Re-labeled PEGylated nanoliposome ((188)Re-liposome) was prepared and evaluated as a therapeutic agent for glioma. MATERIALS AND METHODS: The reporter cell line, F98(luc) was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of (188)Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered (188)Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the (188)Re-liposome-treated rats. RESULTS: By using bioluminescent imaging, the well-established reporter cell line (F98(luc)) showed a high relationship between cell number and its bioluminescent intensity (R(2)=0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of (188)Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the (188)Re-liposome-treated group than the control group (P<0.05). As a result, the lifespan of glioma-bearing rats treated with (188)Re-liposome was prolonged 10.67% compared to the control group. CONCLUSION: The radiotherapeutic evaluation by dosimetry and survival studies have demonstrated that passive targeting (188)Re-liposome via systemic administration can significantly prolong the lifespan of orthotopic glioma-bearing rats while maintaining reasonable systemic radiation safety. Therefore, (188)Re-liposome could be a potential therapeutic agent for glioblastoma multiforme treatment.

99mTc pyrene derivative complex causes double-strand breaks in dsDNA mainly through cluster-mediated indirect effect in aqueous solution.

Radiation therapy for cancer patients works by ionizing damage to nuclear DNA, primarily by creating double-strand breaks (DSB). A major shortcoming of traditional radiation therapy is the set of side effect associated with its long-range interaction with nearby tissues. Low-energy Auger electrons have the advantage of an extremely short effective range, minimizing damage to healthy tissue. Consequently, the isotope 99mTc, an Auger electron source, is currently being studied for its beneficial potential in cancer treatment. We examined the dose effect of a pyrene derivative 99mTc complex on plasmid DNA by using gel electrophoresis in both aqueous and methanol solutions. In aqueous solutions, the average yield per decay for double-strand breaks is 0.011±0.005 at low dose range, decreasing to 0.0005±0.0003 in the presence of 1 M dimethyl sulfoxide (DMSO). The apparent yield per decay for single-strand breaks (SSB) is 0.04±0.02, decreasing to approximately a fifth with 1 M DMSO. In methanol, the average yield per decay of DSB is 0.54±0.06 and drops to undetectable levels in 2 M DMSO. The SSB yield per decay is 7.2±0.2, changing to 0.4±0.2 in the presence of 2 M DMSO. The 95% decrease in the yield of DSB in DMSO indicates that the main mechanism for DSB formation is through indirect effect, possibly by cooperative binding or clustering of intercalators. In the presence of non-radioactive ligands at a near saturation concentration, where radioactive Tc compounds do not form large clusters, the yield of SSB stays the same while the yield of DSB decreases to the value in DMSO. DSBs generated by 99mTc conjugated to intercalators are primarily caused by indirect effects through clustering.

In vitro and in vivo evaluation of lactoferrin-conjugated liposomes as a novel carrier to improve the brain delivery.

In this study, lactoferrin-conjugated PEGylated liposomes (PL), a potential drug carrier for brain delivery, was loaded with radioisotope complex, 99mTc labeled N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (99mTc-BMEDA) for in vitro and in vivo evaluations. The hydrophilicity of liposomes was enhanced by PEGylation which was not an ideal brain delivery system for crossing the blood brain barrier (BBB). With the modification of a brain-targeting ligand, lactoferrin (Lf), the PEGylated liposome (PL) might become a potential brain delivery vehicle. In order to test the hypothesis in vitro and in vivo, 99mTc-BMEDA was loaded into the liposomes as a reporter with or without Lf-conjugation. The mouse brain endothelia cell line, bEnd.3 cells, was cultured to investigate the potential uptake of liposomes in vitro. The in vivo uptake by the mouse brain of the liposomes was detected by tissue biodistribution study. The results indicated that Lf-conjugated PEGylated liposome showed more than three times better uptake efficiency in vitro and two-fold higher of brain uptake in vivo than PEGlyated liposome. With the success of loading the potential Single Photon Emission Tomography (SPECT) imaging probe, 99mTc-BMEDA, Lf-PL might serve as a promising brain delivery system for loading diagnostics or therapeutics of various brain disorders.

Imaging, autoradiography, and biodistribution of (188)Re-labeled PEGylated nanoliposome in orthotopic glioma bearing rat model.

The (188)Re-labeled pegylated nanoliposome (abbreviated as (188)Re-Liposome) was prepared and evaluated for its potential as a theragnostic agent for glioma. (188)Re-BMEDA complex was loaded into the pegylated liposome core with pH 5.5 ammonium sulfate gradient to produce (188)Re-Liposome. Orthotopic Fischer344/F98 glioma tumor-bearing rats were prepared and intravenously injected with (188)Re-Liposome. Biodistribution, pharmacokinetic study, autoradiography (ARG), histopathology, and nano-SPECT/CT imaging were conducted for the animal model. The result showed that (188)Re-Liposome accumulated in the brain tumor of the animal model from 0.28%±0.09% injected dose (ID)/g (n=3) at 1 hour to a maximum of 1.95%±0.35% ID/g (n=3) at 24 hours postinjection. The tumor-to-normal brain uptake ratio (T/N ratio) increased from 3.5 at 1 hour to 32.5 at 24 hours. Both ARG and histopathological images clearly showed corresponding tumor regions with high T/N ratios. Nano-SPECT/CT detected a very clear tumor image from 4 hours till 48 hours. This study reveals the potential of (188)Re-Liposome as a theragnostic agent for brain glioma.

[Study on origin of meridians and collaterals through pain relieving effect of muscle regions].

Through analysis on sequencing of meridians and their muscle regions, their pertaining organs, run ning courses, linking and indications described in Zubi Shiyimai (Eleven Meridian of Foot and Hand), Yinyang Shiyimai (Eleven Meridian of Yinyang), Lingshu: Jingmai (Miraculous Pivot: Meridian) and Lingshu: Jinjing (Miraculous Pivot: Muscle Meridian), it is found that most of the indications of acupuncture in ancient time are symptoms of the muscle regions. 62.59% points of the national standard acupoints location close to tender points of the muscle regions, which indicates that the origin of early acupoints are tender points along the running courses of the muscle regions. Thus, it is concluded that meridians and their muscle regions have the same origin, which provides new train of thinking for a better comprehension of origin of meridians and collaterals.

Development of a thermosensitive hydrogel system for local delivery of (188)Re colloid drugs.

A novel internal radiation therapy (IRT) mode intended for controlled local delivery of (188)Re-Tin colloid was developed by using chitosan-based thermosensitive hydrogel. Chitosan (C) and beta-glycerophosphate (beta-GP) were used to prepare the thermosensitive hydrogel (C/GP). The prepared C/GP hydrogel featured a rapid sol-gel transition within 5min after it was brought into an environment of 37 degrees C. (188)Re-Tin colloid was prepared with labeling efficiency of 93.9+/-0.6%, and could be increased to more than 98% following centrifugation. The average particle size of (188)Re-Tin colloid was 12.1+/-1.2microm, with only 7.2+/-1.5% less than 1microm. Scintigraphic study showed that (188)Re-Tin colloid contained in the C/GP hydrogel was localized (>91%) around the injection site for up to 48h post injection, verifying the intended function of the IRT design. The developed novel form of IRT in this study could be an effective treatment mode for regional radiotherapy.