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Exposure to organophosphate esters (OPEs) is associated with several chronic diseases, but the relationship with mortality risk is unclear. Therefore, we used the National Health and Nutrition Examination Survey 2011-2018 data to evaluate these relationships. 6,869 participants aged 18 years or older were included. Survival status information was obtained through the National Death Index through 31 December 2019. Multivariable COX regression model was adopted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships of urinary OPEs metabolites with mortality risk. During an average of 5.0 years of follow-up, 406 deaths were documented. After adjusting for confounders, bis(2-chloroethyl) phosphate was associated with an increased risk of all-cause mortality [HR (95%CI) = 1.12(1.05-1.20)] and cardiovascular mortality [HR (95%CI) = 1.15(1.04-1.26)]. Our study found that exposure to OPEs was significantly associated with increased risks of all-cause and cardiovascular mortality. Consequently, controlling OPEs exposure is needed to alleviate the health-related burden.
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Low mechanical strength is still the key question for collagen hydrogel consisting of nanofibrils as hard tissue repair scaffolds with no loss of biological function. In this work, novel collagen nanofibrous hydrogels with high mechanical strength were fabricated based on the pre-protection of trisodium citrate masked Zr(SO4)2 solution for collagen self-assembling nanofibrils and then further coordination with Zr(SO4)2 solution. The mature collagen nanofibrils with d-period were observed in Zr(IV) mediated collagen hydrogels by AFM when the Zr(IV) concentration was ≥ 10 mmol/L, and the distribution of zirconium element was uniform. Due to the coordination of Zr(IV) with âCOOH, âNH2 and âOH within collagen and the tighter entanglement of collagen nanofibrils, the elastic modulus and compressive strength of Zr(IV) mediated collagen nanofibrous hydrogel were 208.3 and 1103.0 kPa, which were approximate 77 and 12 times larger than those of pure collagen hydrogel, respectively. Moreover, the environmental stability such as thermostability, swelling ability and biodegradability got outstanding improvements and could be regulated by Zr(IV) concentration. Most importantly, the resultant hydrogel showed excellent biocompatibility and even accelerated cell proliferation.
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Proliferação de Células , Colágeno , Hidrogéis , Nanofibras , Zircônio , Hidrogéis/química , Zircônio/química , Nanofibras/química , Colágeno/química , Proliferação de Células/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Tamanho da Partícula , Força Compressiva , Propriedades de SuperfícieRESUMO
Cytochrome P450 (CYP) enzymes are crucial for the detoxification of xenobiotics, cellular metabolism, and homeostasis. This study investigated the molecular characterization of CYP enzymes in the black-spotted frog, Pelophylax nigromaculatus, and examined the regulation of CYP expression in response to chronic exposure to the antibiotic sulfamethoxazole (SMX) at various environmental concentrations (0, 1, 10, and 100 µg/L). The full-length cDNA of Pn-CYP26B1 was identified. The sequence included open reading frames of 1,536 bp, encoding proteins comprising 511 amino acids. The signature motif, FxxGxxxCxG, was highly conserved when compared with a number of selected animal species. SMX significantly upregulated the expression of the protein CYP26B1 in frog livers at concentrations of 1 and 10 µg/L. SMX showed an affinity for CYP26B1 of -7.6 kcal/mol, indicating a potential mechanism for SMX detoxification or adaptation of the frog. These findings contributed to our understanding of the environmental impact of antibiotics on amphibian species and underscored the importance of CYP enzymes in maintaining biochemical homeostasis under exposure to xenobiotic stress.
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The efficacy of Adoptive Cell Transfer Therapy (ACT) in combating hematological tumors has been well-documented, yet its application to solid tumors faces formidable hurdles, chief among them being the suboptimal therapeutic response and the immunosuppressive milieu within the tumor microenvironment (TME). Recently, Garcia, J. et al. present compelling findings shedding light on potential breakthroughs in this domain. Their investigation reveals the pronounced augmentation of anti-tumor activity in CAR T cells through the introduction of a T cell neoplasm fusion gene, CARD11-PIK3R3. The incorporation of this gene into engineered T cell therapy holds promise as a formidable tool in the arsenal of cancer immunotherapy. The innovative strategy outlined not only mitigates the requirement for high doses of CAR T cells but also enhances tumor control while exhibiting encouraging safety profiles. The exploration of the CARD11-PIK3R3 fusion gene represents an advancement in our approach to bolstering the anti-tumor efficacy of immunotherapeutic interventions. Nonetheless, the imperative for further inquiry to ascertain its transfection efficiency and long-term safety cannot be overstated. Nevertheless, this seminal investigation offers a beacon of hope in surmounting the formidable treatment impediments posed by solid tumors, paving the way for a transformative era in cancer therapeutics.
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Imunoterapia Adotiva , Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Neoplasias/terapia , Neoplasias/genética , Neoplasias/imunologia , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Microambiente Tumoral/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , AnimaisRESUMO
In the present study, the aim was to evaluate the clinical efficacy and safety of low-dose venetoclax combined with azacitidine for the treatment of older and frail patients with newly diagnosed acute myeloid leukaemia (AML). Data of 26 older patients with newly diagnosed AML admitted to Yuyao People's Hospital (Yuyao, China) between January 2021 and May 2023 were retrospectively analysed. The treatment regimens were as follows: Subcutaneous injection of 100 mg azacitidine on days 1-5 and 100 mg oral venetoclax on days 3-16 or 200 mg oral venetoclax on days 3-30. The median age of the 26 patients was 73 years. After the first course of treatment, the complete remission (CR) and CR with incomplete haematological recovery rate was 84.6%, and the objective response rate was 96.2%. The most common adverse events noted during treatment were haematological adverse events including grade 3/4 granulocytosis (57.7%), febrile neutropenia (30.8%), pulmonary infection (32.0%), thrombocytopenia (42.3%) and anaemia (42.3%). A total of 13 (50.0%) patients did not require platelet (PLT) infusion during treatment. The main non-haematological adverse reactions included gastrointestinal reactions such as nausea, vomiting and diarrhoea. Patients were followed up until December 2023, with a median follow-up time of 9.5 months (range, 1.9-26.0 months). Of the 26 patients, nine (34.6%) patients experienced relapse, with a mean recurrence time of 5.9 months. In conclusion, preliminary results indicated that low-dose venetoclax combined with azacitidine is effective and safe for the treatment of older and frail patients with newly diagnosed AML, providing a new treatment option for these patients.
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Low-cost formate salt was used as the reductant and part of the carboxyl source in a visible-light-driven dicarboxylation of diverse alkenes, including simple styrenes. The highly competing hydrocarboxylation side reaction was successfully overridden. Good yields of products were obtained under mild reaction conditions at ambient temperature and pressure of CO2. The dual role of formate salt may stimulate the discovery of a range of new transformations under mild and friendly conditions.
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At present, the situation regarding heavy metal pollution in aquatic environments is becoming more and more serious. The bioaccumulation of heavy metals in aquatic plants causes obvious phytotoxicity, which can also induce secondary pollution in the aquatic environment. Zinc and copper, as indispensable elements for plant growth, are also prominent heavy metals in water pollution in China, and their concentrations play a crucial role in plant growth. In this study, we investigated the response of Pistia stratiotes (P. stratiotes) to different concentrations of Zn and Cu, and the results showed that plant growth and photosynthesis were inhibited under both Zn (1, 2, 4, and 8 mg/L) and Cu (0.2, 0.4, 0.8, and 1 mg/L) stresses. The relative growth rates of P. stratiotes under 8 mg/L Zn or 1 mg/L Cu stress were 6.33% and 6.90%, which were much lower than those in the control group (10.86%). Meanwhile, Zn and Cu stress caused insignificant change in the relative water contents of plants. The decrease in phlorophyll fluorescence parameters and chlorophyll contents suggested the significant photoinhibition of Zn and Cu stress. Chemical analysis of plant root exudates showed that the root secretion species obtained by gas chromatography-mass spectrometry (GC-MS) mainly included amino acids, alkanes, aldehydes, ketones, phenols, and more. Compared with the control group, the influence of Zn or Cu on the reduction in relative amounts of exudates was greater than that on the increase. The results of this study provide important data for the utilization of P. stratiotes in heavy metal-polluted water environments.
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CLLU1, a disease-specific gene associated with chronic lymphoid leukemia (CLL), is located on chromosome 12q22. Previous studies considered CLLU1 to be a non-coding RNA; however, recent research has discovered that its coding sequence region possesses the potential to encode a short peptide similar to interleukin-4. Remarkably, abnormally elevated expression of CLLU1 has only been detected in chronic lymphoid leukemia among all hematological cancers. High CLLU1 expression often indicates more malignant pathological features and an unfavorable prognosis for patients. Importantly, the expression level of CLLU1 remains unaffected by the passage of time or therapeutic interventions, thus rendering it a novel prognostic marker. This article provides a comprehensive summary of relevant research findings on CLLU1 in the context of CLL prognosis and clinical applications, aiming to guide subsequent theoretical and clinical investigations in this field.
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Leucemia Linfocítica Crônica de Células B , RNA Longo não Codificante , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Proteínas de Neoplasias/genética , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Genes NeoplásicosRESUMO
The marked salinity and alkaline pH of coastal saline soil profoundly impact the nitrogen conversion process, leading to a significantly reduced nitrogen utilization efficiency and substantial gaseous nitrogen loss. The application of soil amendments (e.g. biochar, manure, and gypsum) was proved to be effective for the remediation of saline soils. However, the effects of the three amendments on soil nitrogen transformation in soils with various salinity levels, especially on NH3 volatilization and N2O emission, remain elusive. Here, we reported the effects of biochar, manure, and gypsum on NH3 volatilization and N2O emission under four natural salinity gradients in the Yellow River Delta. Also, high-throughput sequencing and qPCR analysis were performed to characterize the response of nitrification (amoA) and denitrification (nirS, nirK, and nosZ) functional genes to the three amendments. The results showed that the three amendments had little effect on NH3 volatilization in low- and moderate-salinity soils, while biochar stimulated NH3 volatilization in high-salinity soils and reduced NH3 volatilization in severe-salinity soils. Spearman correlation analysis demonstrated that AOA was significantly and positively correlated with the NO3--N content (r = 0.137, P < 0.05) and N2O emissions (r = 0.174, P < 0.01), which indicated that AOA dominated N2O emissions from nitrification in saline soils. Structural equation modeling indicated that biochar, manure, and gypsum affected N2O emission by influencing soil pH, conductivity, mineral nitrogen content, and functional genes (AOA-amoA and nosZ). Two-way ANOVA further showed that salinity and amendments (biochar, manure, and gypsum) had significant effects on N2O emissions. In summary, this study provides valuable insights to better understand the effects of gaseous N changes in saline soils, thereby improving the accuracy and validity of future GHG emission predictions and modeling.
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Desnitrificação , Nitrificação , Óxido Nitroso/análise , Volatilização , Sulfato de Cálcio , Esterco , Salinidade , Microbiologia do Solo , Carvão Vegetal/química , Solo/química , Nitrogênio/análiseRESUMO
Since the COVID-19 pandemic, face masks have been used popularly and disposed of improperly, leading to the generation of a large amount of microplastics. The objective of this review is to provide a comprehensive insight into the characteristics of mask-derived microplastics, the influential factors of microplastics release, and the potential risks of these microplastics to the environment and organisms. Mask-derived microplastics were predominantly transparent fibers, with a length of <1 mm. The release of microplastics from masks is mainly influenced by mask types, use habits, and weathering conditions. Under the same conditions, surgical masks release more microplastics than other types of masks. Long-term wearing of masks and the disinfection for reuse can promote the release of microplastics. Environmental media, UV irradiation, temperature, pH value, and mechanical shear can also influence the microplastics release. The risks of mask-derived microplastics to human health via inhalation cannot be neglected. Future studies should pay more attention to the release of microplastics from the masks with alternative materials and under more weathering conditions.
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COVID-19 , Máscaras , Humanos , Microplásticos , Pandemias , PlásticosRESUMO
In recent years, water quality deterioration caused by harmful algal blooms (HABs) has become one of the global drinking water safety issues, and sulfate radical driven heterogeneous advanced oxidation technology has been widely used for algae removal. However, the shortages of low active site exposure, metal leaching, and secondary contamination limit its further application. Therefore, the single-atom Mn anchored on inorganic carbon nitride was constructed to enhance the oxidation and coagulation of algal cells while maintaining cell integrity in this study. The removal efficiency of Microcystis aeruginosa was as high as 100 % within 30 min under the optimal conditions of 400 mg/L single-atom Mn-embedded g-C3N4 (SA-MCN) and 0.32 mM peroxymonosulfate (PMS). Importantly, the K+ release, malondialdehyde concentration, floccules morphology and variation of algal organic matters further showed that the algal cells still maintained high integrity without severe rupture during the catalytic reaction. Furthermore, the catalytic mechanisms of algae removal by moderate oxidation and simultaneous coagulation in this system were explored by quenching experiments, EPR analysis, theoretical calculation, and Zeta potential. In brief, this study highlighted the single-atom heterogeneous catalyst with high-efficiency and environmental-friendliness in harmful algal blooms control.
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Proliferação Nociva de Algas , Microcystis , Nitrilas , PeróxidosRESUMO
Food allergy (FA) is a common immune disorder that involves dysfunctional immune regulation. More remedies for restoring immune regulation are necessary. Semaphorin 3 A (Sema3a) is a secreted protein of the semaphorin family, which plays a role in immune responses at all stages. The objective of this study is to gain an understanding of how Sema3a can restore the immune regulatory abilities of type 1 regulatory T cells (Tr1 cells). In this study, blood samples were taken from patients with FA. Tr1 cells were purified from blood samples using flow cytometry cell sorting, using LAG3 and CD49b as surface markers. RNA sequencing was employed to examine the characteristics of Tr1 cells. We observed an exaggerated increase in ER stress in peripheral Tr1 cells of FA patients. Enforced expression of spliced X-box protein-1 (XBP1s, one of the key molecules in ER stress) resulted in suppression of interleukin (IL)-10 expression in CD4+ T cells. Eukaryotic initiation factor 2a (eIF2a) mediated the effects of XBP1 on suppressing IL-10 expression in Tr1 cells. The use of Sema3a resulted in a decrease in ER stress, and an increase in IL-10 expression in Tr1 cells of FA patients. Sema3a administration reduced experimental FA by increasing the number of Tr1 cells. In conclusion, IL-10 expression in Tr1 cells is disturbed by ER stress. Sema3a treatment restores the expression of IL-10 and the immunosuppressive capability of Tr1 cells.
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Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) have been widely used as flame retardants. However, their potential health risks to organisms have raised concerns, particularly for liver toxicity. Present study aimed to explore the toxic effects of TCBPA and TBBPA on black-spotted frogs (Pelophylax nigromaculatus) liver oxidative stress, autophagy, and lipid accumulation. After exposure to 0.001, 0.01, 0.1, and 1 mg/L TBBPA and TCBPA for 14 days, the content of cholesterol and triglyceride were significantly elevated. In addition, the malondialdehyde level rose greatly in dose dependent. However, the glutathione level declined in high TBBPA groups (0.01 and 0.1 mg/L). Furthermore, expressions of Beclin1, Atg5, and Atg7 were significantly increased, while p62 was markedly declined, respectively. Results obstained suggested that TBBPA and TCBPA exposure induced liver toxicity in black-spotted frog. This study provided insights into the toxicity mechanism of bisphenol flame retardants in amphibians and will aid in the ecological risk assessment of flame retardants.
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The purpose of this study was to evaluate L-cysteine-modified transfersomes as the topical carrier for enhanced epidermal delivery of podophyllotoxin (POD). L-cysteine-deoxycholic acid (LC-DCA) conjugate was synthesized via an amidation reaction. POD-loaded L-cysteine-modified transfersomes (POD-LCTs) were prepared via a thin membrane dispersion method and characterized for their particle size, zeta potential, morphology, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and in vitro release. Subsequently, in vitro skin permeation and retention, fluorescence distribution in the skin, hematoxylin-eosin staining and in vivo skin irritation were studied. The POD-LCTs formed spherical shapes with a particle size of 172.5 ± 67.2 nm and a zeta potential of -31.3 ± 6.7 mV. Compared with the POD-Ts, the POD-LCTs provided significantly lower drug penetration through the porcine ear skin and significantly increased the skin retention (p < 0.05). Meaningfully, unlike the extensive distribution of the POD-loaded transfersomes (POD-Ts) throughout the skin tissue, the POD-LCTs were mainly located in the epidermis. Moreover, the POD-LCTs did not induce skin irritation. Therefore, the POD-LCTs provided an enhanced epidermal delivery and might be a promising carrier for the topical delivery of POD.
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Cisteína , Podofilotoxina , Animais , Suínos , Administração Cutânea , Podofilotoxina/farmacologia , Pele , Epiderme , Tamanho da Partícula , Portadores de Fármacos/química , Sistemas de Liberação de MedicamentosRESUMO
Sulfate radical mediated advanced oxidation processes (SR-AOPs) have emerged as a promising alternative for emerging contaminants degradation. However, high activity and great stability are commonly difficult to juggle, and the structure-activity correlations are still ambiguous. This study constructed the cubic CaTiO3 perovskite modified by highly-dispersed cobalt for peroxymonosulfate (PMS) activation to improve the specific lattice plane exposure and reduce the metal leaching simultaneously. 98% of amitriptyline (AMT) degradation was achieved within 60 min under the condition of 200 mg/L Co0.1-CTO and 100 mg/L PMS. The results indicated that surface Co2+/Co3+ redox couple and lattice oxygen were responsible for PMS activation, and the evolution of ·OH, SO4·- and 1O2 were revealed. According to density functional theory (DFT) calculations, the highly-dispersed Co on cubic surface effectively captured PMS and promoted electron transfer for the generation of ·OH and SO4·-, while more oxygen atoms exposed on Co0.1-CTO(200) surface facilitated the generation of 1O2. Briefly, this study provides a novel strategy of catalyst synthesis in PMS activation for water treatment.
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Cobalto , Óxidos , Peróxidos , Oxigênio , Preparações FarmacêuticasRESUMO
Curcumin (Cur) is a kind of polyphenol with a variety of topical pharmacological properties including antioxidant, analgesic and anti-inflammatory activities. However, its low water solubility and poor skin bioavailability limit its effectiveness. In the current study, we aimed to develop microemulsion-based keratin-chitosan gel for the improvement of the topical activity of Cur. The curcumin-loaded microemulsion (CME) was formulated and then loaded into the keratin-chitosan (KCS) gel to form the CME-KCS gel. The formulated CME-KCS gel was evaluated for its characterization, in vitro release, in vitro skin permeation and in vivo activity. The results showed that the developed CME-KCS gel had an orange-yellow and gel-like appearance. The particle size and zeta potential of the CME-KCS gel were 186.45 ± 0.75 nm and 9.42 ± 0.86 mV, respectively. The CME-KCS gel showed desirable viscoelasticity, spreadability, bioadhesion and controlled drug release, which was suitable for topical application. The in vitro skin permeation and retention study showed that the CME-KCS gel had better in vitro skin penetration than the Cur solution and achieved maximum skin drug retention (3.75 ± 0.24 µg/cm2). In vivo experimental results confirmed that the CME-KCS gel was more effective than curcumin-loaded microemulsion (Cur-ME) in analgesic and anti-inflammatory activities. In addition, the CME-KCS gel did not cause any erythema or edema based on a mice skin irritation test. These findings indicated that the developed CME-KCS gel could improve the skin penetration and retention of Cur and could become a promising formulation for topical delivery to treat local diseases.
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Duck circovirus (DuCV) is one of the most prevalent viruses in the duck breeding industry, and causes persistent infection and severe immunosuppression. Currently, there is a serious lack of prevention and control measures and no commercial vaccine against DuCV. Therefore, effective antiviral drugs are important for treating DuCV infection. Interferon (IFN) is an important component of antiviral innate immunity, but it remains unclear whether duck IFN-α has a clinical effect against DuCV. Antibody therapy is an important way to treat viral infections. The DuCV structural protein (cap) is immunogenic, and it remains to be determined whether an anti-cap protein antibody can effectively block DuCV infection. In this study, the duck IFN-α gene and the DuCV structural protein cap gene were cloned, expressed and purified in Escherichia coli to prepare duck recombinant IFN-α and the cap protein. Then, rabbits were immunized with the recombinant cap protein to prepare a rabbit polyclonal antibody. This study investigated the antiviral effect of duck recombinant IFN-α and the anti-cap protein antibody and their combined effect on Cherry Valley ducks infected with DuCV. The results showed that the treatment significantly alleviated the clinical symptoms of immune organ atrophy and immunosuppression compared with the control. The histopathological damage of the target organs was alleviated, and replication of DuCV in the immune organs was significantly inhibited. The treatment also reduced the damage caused by DuCV to the liver and immune function, and increased the level of the DuCV antibody in the blood, thereby improving antiviral activity. Notably, the combination of duck IFN-α and the polyclonal antibody completely blocked DuCV infection after 13 days under the experimental conditions, showing a better inhibitory effect on DuCV infection than single treatments. These results showed that duck recombinant IFN-α and the anti-cap protein antibody can be used as antiviral drugs to clinically treat and control DuCV infection, particularly the vertical transmission of the virus in breeding ducks.
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Infecções por Circoviridae , Circovirus , Doenças das Aves Domésticas , Animais , Coelhos , Interferon-alfa/genética , Circovirus/genética , Proteínas Recombinantes/genética , Escherichia coli/genética , Infecções por Circoviridae/prevenção & controle , Infecções por Circoviridae/veterinária , Antivirais/farmacologia , Anticorpos , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/prevenção & controleRESUMO
BACKGROUND: The failure of novel therapies effective in preclinical animal models largely reflects the fact that current models do not really mimic the pathological/therapeutic features of glioblastoma (GBM), in which the most effective temozolomide chemoradiotherapy (RT/TMZ) regimen can only slightly extend survival. How to improve RT/TMZ efficacy remains a major challenge in clinic. METHODS: Syngeneic G422TN-GBM model mice were subject to RT/TMZ, surgery, piperlongumine (PL), αPD1, glutathione. Metabolomics or transcriptomics data from G422TN-GBM and human GBM were used for gene enrichment analysis and estimation of ROS generation/scavenging balance, oxidative stress damage, inflammation and immune cell infiltration. Overall survival, bioluminescent imaging, immunohistochemistry, and immunofluorescence staining were used to examine therapeutic efficacy and mechanisms of action. RESULTS: Here we identified that glutathione metabolism was most significantly altered in metabolomics analysis upon RT/TMZ therapies in a truly refractory and reliable mouse triple-negative GBM (G422TN) preclinical model. Consistently, ROS generators/scavengers were highly dysregulated in both G422TN-tumor and human GBM. The ROS-inducer PL synergized surgery/TMZ, surgery/RT/TMZ or RT/TMZ to achieve long-term survival (LTS) in G422TN-mice, but only one LTS-mouse from RT/TMZ/PL therapy passed the rechallenging phase (immune cure). Furthermore, the immunotherapy of RT/TMZ/PL plus anti-PD-1 antibody (αPD1) doubled LTS (50%) and immune-cured (25%) mice. Glutathione completely abolished PL-synergistic effects. Mechanistically, ROS reduction was associated with RT/TMZ-resistance. PL restored ROS level (mainly via reversing Duox2/Gpx2), activated oxidative stress/inflammation/immune responses signature genes, reduced cancer cell proliferation/invasion, increased apoptosis and CD3+/CD4+/CD8+ T-lymphocytes in G422TN-tumor on the basis of RT/TMZ regimen. CONCLUSION: Our findings demonstrate that PL reverses RT/TMZ-reduced ROS and synergistically resets tumor microenvironment to cure GBM. RT/TMZ/PL or RT/TMZ/PL/αPD1 exacts effective immune cure in refractory GBM, deserving a priority for clinical trials.
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Glioblastoma , Glioma , Humanos , Animais , Camundongos , Glioblastoma/tratamento farmacológico , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Espécies Reativas de Oxigênio , Linfócitos T CD8-Positivos , Estresse Oxidativo , Quimiorradioterapia , Microambiente TumoralRESUMO
Both microplastics (MPs) and excess boron (B) have adverse effects on microalgae. However, the combined toxic effects of MPs and excess B on microalgae have not been studied. The aim of this study was to investigate the combined effects of excess B and three types of surface-modified microplastics, including plain polystyrene (PS-Plain), amino-modified polystyrene (PS-NH2), and carboxyl-modified polystyrene (PS-COOH), on chlorophyll a content, oxidative damage, photosynthetic activity and microcystin (MC) production in Microcystis aeruginosa. The results showed that PS-NH2 inhibited the growth of M. aeruginosa, with the maximum inhibition rate of 18.84 %, while PS-COOH and PS-Plain showed stimulatory effects with the maximum inhibition rates of -2.56 % and - 8.03 % respectively. PS-NH2 aggravated the inhibition effects of B, while PS-COOH and PS-Plain alleviated the inhibition effects. Furthermore, the combined exposure of PS-NH2 and excess B had a much greater effect on oxidative damage, cell structure, and production of MCs in algal cells than the combined effects of PS-COOH and PS-Plain. The charges on microplastics affected both B adsorption on microplastics and the aggregation of microplastics with algal cells, indicating that the charge on microplastics is a dominant factor influencing the combined effects of microplastics and excess B on microalgae. Our findings can provide direct evidence for the combined effects of microplastics and B on freshwater algae and improve the understanding of the potential risks of microplastics in aquatic ecosystems.
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Microalgas , Microcystis , Poluentes Químicos da Água , Microplásticos/toxicidade , Microplásticos/química , Plásticos/toxicidade , Poliestirenos/toxicidade , Clorofila A , Boro/toxicidade , Ecossistema , Poluentes Químicos da Água/químicaRESUMO
Duck circovirus (DuCV) is one of the most prevalent infectious viruses in the duck industry in China. Although the clinical symptoms vary, it often causes immunosuppression in the host and leads to secondary infection with other pathogens. Fowl adenovirus serotype 4 (FAdV-4) mainly infects chickens and causes hydropericardium hepatitis syndrome. However, the incidence of infection in ducks has increased in recent years, and the phenomenon of mixed infection with DuCV is very common, resulting in more severe clinical morbidity. However, there is no systematic study evaluating the presence of mixed infection. To explore the synergistic pathogenicity of DuCV and FAdV-4 co-infection in Cherry Valley ducks, a comparative experiment was established between DuCV and FAdV-4 co-infection and single infection animal models. It was found that DuCV and FAdV-4 co-infected ducks showed more pronounced clinical signs of pericardial effusion, hepatitis and immunosuppression; more severe tissue damage in target organs; and more significant levels of viral load, biochemical indicators and immune indicators in various organs compared with Cherry Valley ducks infected with just one virus. The results showed that co-infection with DuCV and FAdV-4 may promote greater viral replication, causing more severe tissue damage and immunosuppression than infection with just one virus. Therefore, the monitoring and prevention of the two viruses should be strengthened clinically, with a particular focus on the potential harm of DuCV as it carries the highest infection rate.