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The incidence and mortality of cancer are the major health issue worldwide. Apart from the treatments developed to date, the unsatisfactory therapeutic effects of cancers have not been addressed by broadening the toolbox. The advent of immunotherapy has ushered in a new era in the treatments of solid tumors, but remains limited and requires breaking adverse effects. Meanwhile, the development of advanced technologies can be further boosted by gene analysis and manipulation at the molecular level. The advent of cutting-edge genome editing technology, especially clustered regularly interspaced short palindromic repeats (CRISPR-Cas9), has demonstrated its potential to break the limits of immunotherapy in cancers. In this review, the mechanism of CRISPR-Cas9-mediated genome editing and a powerful CRISPR toolbox are introduced. Furthermore, we focus on reviewing the impact of CRISPR-induced double-strand breaks (DSBs) on cancer immunotherapy (knockout or knockin). Finally, we discuss the CRISPR-Cas9-based genome-wide screening for target identification, emphasis the potential of spatial CRISPR genomics, and present the comprehensive application and challenges in basic research, translational medicine and clinics of CRISPR-Cas9.
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Sistemas CRISPR-Cas , Neoplasias , Humanos , Terapia Genética , Edición Génica , Inmunoterapia , Neoplasias/genética , Neoplasias/terapiaRESUMEN
Metal contamination in agricultural soils has received widespread attention; however, the status of beryllium (Be) contamination in agricultural soils has been inadequately studied. This research was conducted to determine the enrichment level and major sources of Be contamination in the agricultural soil in Qingcheng District, Qingyuan City, and to quantify the potential ecological risk and human health risk (PER and HHR) of Be by integrating geological mineral and remote-sensing image maps. The results of principal component analysis followed by multiple linear regression (PCA-MLR) suggest that Be, Sn, Zn, Pb, As, and Cd are mainly derived from anthropogenic activities; V, Ti, Sc, Cr, and Co are mainly derived from medium acidic granites; Al and Si are mainly derived from geological sources; and K and Na are mainly derived from calcium-alkaline materials. Anthropogenic activities are priority material sources owing to the highest contribution. Be contamination poses a slight PER, and the PER level of agricultural soil was moderate. The HHR caused by Be is negligible. The results of this study can serve as the basis for promoting agricultural soil protection and developing and implementing agricultural policies to reduce environmental pollution in the study area.
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A total of 511 topsoils and 139 deep soil samples were collected to analyze the distribution characteristics, regional differentiation factors, and contamination sources of Cd in Shantou City, and to assess its environmental, ecological, and human health risks. We used a combination of multivariate statistics and geostatistics to quantify the distribution and level of Cd contamination in the study area, and an absolute principal component scores-multiple linear regression model to resolve the sources of contamination and their contribution values, combined with the health risk model to assess the human health risk from each source. The result exhibited that the average value of soil Cd content was 0.100 mg/kg, which was lower than the threshold value of soil environmental quality standard, but higher than the 0.070 mg/kg background value of soil. The high-value areas of surface Cd content in the study area were distributed in the western, northern, and northeastern parts of Shantou, and the source of Cd in the soil was a mix of anthropogenic and natural contamination. The non-carcinogenic and carcinogenic risks of heavy metal Cd exposure pathways are: oral ingestion > dermal contact > inhalation. The human health risk posed by Cd is below the reference threshold, indicating that the Cd contents in the soil have no unacceptable health risk to the residents. Among industrial sources, natural sources, and unknown sources with potential carcinogenic and non-carcinogenic risks, natural sources were the main source of contamination for adults and children. Among the different soil types, paddy, and red soils had relatively high Cd content, and among the different soil-forming parent materials, the Cd content in soils developed on Quaternary sediments was significantly higher than that other parent materials. Among the different land use types, the Cd content of soil for construction land was the highest. This study provides a scientific foundation and reference for the prevention of soil Cd contamination in Shantou City and the analysis of soil contamination sources in areas with similar contamination patterns.
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Metales Pesados , Contaminantes del Suelo , Adulto , Cadmio/análisis , Niño , China , Monitoreo del Ambiente , Humanos , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisisRESUMEN
Light, one of the most important natural resources for plant species, significantly influences the biomass yield and nutrient uptake capacity in plants. Light sources with different spectra combinations can impact the bioavailability, toxicity, and solubility of heavy metals in soils by altering the concentrations and fractionations of soil dissolved organic matter (DOM). A series of light irradiation treatments were performed to evaluate the influence of red, yellow, and blue lights on the characteristics of DOM in the rhizosphere soils of Arabidopsis thaliana. The results showed that monochromatic red light significantly raised the levels of DOM and proportions of hydrophilic fractionations in the rhizosphere of A. thaliana relative to the control, while monochromatic blue light had the opposite effect. Moreover, the proportions of hydrophobic acid, which can mobilize Cd effectively, also raised with increasing doses of red light, which stimulated Cd mobilization. The application of yellow light not only increased the levels of hydrophobic acid in monochromatic red light treatment but also decreased the proportion of hydrophobic fractions in monochromatic blue light treatment, partially weakening the negative impacts of pure blue light on soil Cd activation. Moreover, DOM from the combined red, yellow, and blue lights resulted in a significantly stronger Cd extraction efficiency than the other light irradiation treatments, consequently enhancing the Cd phytoextraction efficiency of A. thaliana. The findings of this study demonstrated that a suitable light combination could enhance the phytoremediation effect of A. thaliana by activating soil Cd, and this method can be extrapolated to the real field, where light irradiation can be easily applied and modulated.
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Arabidopsis , Contaminantes del Suelo , Biodegradación Ambiental , Cadmio/análisis , Materia Orgánica Disuelta , Rizosfera , Suelo , Contaminantes del Suelo/análisisRESUMEN
Gaogang Town, a typical urban center within the Pearl River Delta region of China, suffers contamination of soils with metals/metalloids due to rapid development of industrial activities and agriculture. Few studies have been conducted to systematically describe the main sources, influencing factors, and ecological risks of metals/metalloids in soils in China. In this study, 312 surface soil samples were collected, and 15 elements were detected by plasma emission spectroscopy, atomic fluorescence spectroscopy, and atomic emission spectrometry. Element content features were analyzed by index of geo-accumulation (Igeo), pollution load index (PLI), potential ecological risk index (RI), positive matrix factorization model (PMF), and geostatistical analysis. The PLI value is between 0 and 1, indicating that the whole study area is lightly polluted. Combining PMF model and geostatistical analysis, soil elements in surface soils of Gaogang town were quantitatively apportioned into four sources: parent material and basic substances (23.5%), natural sources (32.2%), agricultural activities and industrial pollution (22.9%), and transportation (21.4%). The comprehensive analysis results show that polluted areas are mainly distributed on roads, rivers, and industrial and human activity areas. The main sources of ecological risks are factory pollution and human activity. Finally, we found that a quarter of the sampling density was the best sample size for this study.
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Metales Pesados , Contaminantes del Suelo , China , Monitoreo del Ambiente , Humanos , Metales Pesados/análisis , Medición de Riesgo , Suelo/química , Contaminantes del Suelo/análisisRESUMEN
Decapitation and root cutting can influence plant physiological features, such as height, dry weight, and transpiration rate, which partly determine the success of phytoremediation. In this study, the effects of three root cutting intensities (10%, 25%, and 33%), decapitation, and their combination on the phytoremediation efficiency of Celosia argentea were evaluated. Decapitation increased the biomass yield of C. argentea roots and leaves and significantly improved the species' Cd decontamination ability. Root cutting, especially 33% cutting treatment, decreased the root dry weight. The 10% and 25% root cutting treatments increased the leaf biomass yield by 58.6% and 41.4%, respectively, compared with the untreated control, even compensating for the loss of roots, but 33% root cutting decreased the leaf dry weight. Low and moderate root cutting intensity (10% and 25%) increased the leaf Cd content by 33.4% and 24.9%, respectively, and was associated with improved transpiration rate. The highest root and leaf dry weights were observed for the combination of decapitation and 10% root cutting, which increased the biomass yield of underground and aerial parts by 109.9% and 286.2%, respectively. In addition, decapitation offset the negative effects of 33% root cutting on plant growth, indicated by the higher dry weight relative to the control. Decapitated C. argentea accumulated 11.0, 7.5, and 0.7 times more Cd with the 10%, 25%, and 33% root cutting treatments, respectively, compared with the control. The combination of root cutting and decapitation was a practicable and economical method of enhancing the Cd decontamination capacity of C. argentea.
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Biodegradación Ambiental , Celosia , Contaminantes del Suelo/análisis , Biomasa , Decapitación , Raíces de Plantas/química , Plantas , SueloRESUMEN
Objective: To investigate the effects of lycopene-loaded microemulsion (LME) on the cognitive function and neurogenesis in the dentate gyrus (DG) of the hippocampus and subventricular (SVZ) region of rats with amyloid ß- (Aß-) induced Alzheimer's disease (AD) and its mechanism based on the Wnt/ß-catenin pathway. Methods: Healthy Wistar rats were divided into four groups: the blank control (CON), AD control, traditional lycopene (LOO), and LME groups. The CON and AD groups were fed with normal saline, while the LOO group was fed with traditional lycopene, and the LME group was fed with lycopene-loaded microemulsion. Behavioral tests were performed after three weeks of gastric administration. Immunofluorescence-labeled cells were used to observe the differentiation and maturation of new nerve cells in the DG of the hippocampus and SVZ region. qRT-PCR and Western blotting detected the expression of neurogenesis genes and Wnt/ß-catenin pathway-related proteins, respectively. Results: On the Morris water maze test, LME rats had significantly shortened movement trajectory on the searching platform, reduced escape latency time, and increased residence time on the original platform quadrant. In addition, more LME rats crossed the platform when it was removed. Thus, LME can improve the spatial learning and memory of Aß-induced AD rats. On qRT-PCR, LME significantly increased Reelin, Nestin, and Pax6 gene expressions, which regulate neurogenesis. Immunofluorescence showed that LME could significantly increase BrdU+, Dcx+, BrdU+/Neun+, BrdU+/Dcx+ cells in the DG and SVZ regions, thus promoting neurogenesis. LME also reduced the number of Iba1+ and Iba1+/BrdU+ cells, thus reducing the neuroinflammatory response. On Western blot, LME upregulated the Wnt/ß-catenin pathway by upregulating Wnt3a, ß-catenin, Disheveled (Dvl), and p-GSK3ß and downregulating p-ß-catenin and GSK3ß. Conclusion: LME attenuates cognitive impairment in Aß-induced AD rats by promoting neurogenesis in the hippocampus and SVZ region through upregulating the Wnt/ß-catenin pathway.
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Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/toxicidad , Licopeno/administración & dosificación , Neurogénesis/efectos de los fármacos , Fragmentos de Péptidos/toxicidad , Vía de Señalización Wnt/efectos de los fármacos , Enfermedad de Alzheimer/fisiopatología , Animales , Antioxidantes/administración & dosificación , Emulsiones , Hipocampo/citología , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Ventrículos Laterales/efectos de los fármacos , Masculino , Neurogénesis/fisiología , Ratas , Ratas Wistar , Vía de Señalización Wnt/fisiologíaRESUMEN
Rapid, convenient methods for monoclonal antibody (mAb) isolation are critical for determining the concentrations of therapeutic mAbs in human serum. This work uses porous nylon membranes modified with a HER2 peptide mimotope, KGSGSGSQLGPYELWELSH (KH19), for rapid affinity capture of Herceptin, a mAb used to treat breast cancer. Covalent linking of KH19 to poly(acrylic acid)-containing films in porous nylon leads to a Herceptin-binding capacity of 10 mg per mL of membrane and allows selective Herceptin capture from diluted (1:3) human serum in 5 min. Liquid chromatography-mass spectrometry demonstrates the high purity of eluted Herceptin. Moreover, the fluorescence intensity of the protein eluted from membranes increases linearly with the amount of Herceptin spiked in loading solutions containing diluted (1:3) human serum. These results demonstrate the promise of mimotope-modified membranes for Herceptin analysis that does not require secondary antibodies or derivatization with fluorescent labels. Thus, mimotope-containing membranes may form part of a simple benchtop analysis system for assessing the concentrations of therapeutic mAbs.
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Proteínas Inmovilizadas/química , Fragmentos de Péptidos/química , Receptor ErbB-2/química , Trastuzumab/análisis , Trastuzumab/aislamiento & purificación , Adsorción , Humanos , Nylons/química , Tamaño de la Partícula , Porosidad , Propiedades de Superficie , Trastuzumab/sangreRESUMEN
Proteolysis is often a critical step in protein characterization via mass spectrometry. Compared to complete digestion, limited proteolysis gives larger peptides, and the dominant cleavage sites may identify highly accessible, flexible protein regions. This paper explores controlled proteolysis in porous nylon membranes containing immobilized trypsin. Passage of protein solutions through â¼100 µm thick membranes provides reaction residence times as short as milliseconds to limit digestion. Additionally, variation of the membrane pore size and the protease-immobilization method (electrostatic adsorption or covalent anchoring to adsorbed polymer in membrane pores) affords control over the proteolysis rate. When digesting the highly labile protein ß-casein, large membrane pores (5.0 µm) and covalent enzyme anchoring to adsorbed polymer lead to particularly long tryptic peptides. With the more trypsin-resistant proteins cytochrome c and apomyoglobin, in-membrane proteolysis with short residence times, 1.2 µm membrane pores, and trypsin electrostatically immobilized to an adsorbed polyanion cleaves the proteins after lysine residues in flexible regions. For both cytochrome c and apomyoglobin, cleavages in an interhelix region yield two particularly large peptides that cover the entire protein sequence.
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Enzimas Inmovilizadas/química , Proteolisis , Tripsina/química , Adsorción , Apoproteínas/química , Caseínas/química , Citocromos c/química , Mioglobina/química , PorosidadRESUMEN
This paper presents rapid protein purification and proteolysis methods that integrate membrane technology and pipet tips. Pushing a protein-containing solution through a protease-modified membrane at the end of a pipet tip digests proteins in 30 s or less, and the short proteolysis time avoids reformation of disulfide bonds to enable tryptic digestion without alkylation of cysteine residues. Moreover, proteolysis is more complete than digestion for 30 min in solution. Antibody digestion at the end of a pipet tip leads to 100% peptide coverage in MS analyses. Similarly, when membranes contain Ni(2+) complexes, pipetting aqueous polyhistidine-tagged protein through the membrane and subsequent rinsing and elution yield purified polyhistidine-tagged protein in 2 min. These applications demonstrate the potential for combining functional membranes and pipet tips for rapid sample purification and pretreatment.
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Técnicas de Química Analítica/métodos , Membranas Artificiales , Proteínas/aislamiento & purificación , Proteínas/metabolismo , Secuencia de Aminoácidos , Animales , Técnicas de Química Analítica/normas , Complejos de Coordinación/química , Electroforesis en Gel de Poliacrilamida , Espectrometría de Masas , Níquel/química , Péptido Hidrolasas/metabolismo , Proteolisis , Factores de Tiempo , Tripsina/metabolismoRESUMEN
ABSTRACT: Subarachnoid hemorrhage leads to a series of pathological changes, including vascular spasm, cellular apoptosis, blood-brain barrier damage, cerebral edema, and white matter injury. Microglia, which are the key immune cells in the central nervous system, maintain homeostasis in the neural environment, support neurons, mediate apoptosis, participate in immune regulation, and have neuroprotective effects. Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage. Moreover, microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage. Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury. This provides new targets and ideas for the treatment of subarachnoid hemorrhage. However, an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking. This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm, neuroinflammation, neuronal apoptosis, blood-brain barrier disruption, cerebral edema, and cerebral white matter lesions. It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage. Currently, microglia in subarachnoid hemorrhage are targeted with TLR inhibitors, nuclear factor-κB and STAT3 pathway inhibitors, glycine/tyrosine kinases, NLRP3 signaling pathway inhibitors, Gasdermin D inhibitors, vincristine receptor α receptor agonists, ferroptosis inhibitors, genetic modification techniques, stem cell therapies, and traditional Chinese medicine. However, most of these are still being evaluated at the laboratory stage. More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.
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Antibody-drug conjugates (ADCs) are biologically targeted drugs composed of antibodies and cytotoxic drugs connected by linkers. These innovative compounds enable precise drug delivery to tumor cells, minimizing harm to normal tissues and offering excellent prospects for cancer treatment. However, monoclonal antibody-based ADCs still present challenges, especially in terms of balancing efficacy and safety. Bispecific antibodies are alternatives to monoclonal antibodies and exhibit superior internalization and selectivity, producing ADCs with increased safety and therapeutic efficacy. In this review, we present available evidence and future prospects regarding the use of bispecific ADCs for cancer treatment, including a comprehensive overview of bispecific ADCs that are currently in clinical trials. We offer insights into the future development of bispecific ADCs to provide novel strategies for cancer treatment.
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Anticuerpos Biespecíficos , Inmunoconjugados , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Anticuerpos Biespecíficos/uso terapéutico , Inmunoconjugados/uso terapéutico , Antineoplásicos/uso terapéutico , Sistemas de Liberación de Medicamentos , Terapia Molecular DirigidaRESUMEN
Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders that affect individuals' social interactions, communication skills, and behavioral patterns, with significant individual differences and complex etiology. This article reviews the definition and characteristics of ASD, epidemiological profile, early research and diagnostic history, etiological studies, advances in diagnostic methods, therapeutic approaches and intervention strategies, social and educational integration, and future research directions. The highly heritable nature of ASD, the role of environmental factors, genetic-environmental interactions, and the need for individualized, integrated, and technology-driven treatment strategies are emphasized. Also discussed is the interaction of social policy with ASD research and the outlook for future research and treatment, including the promise of precision medicine and emerging biotechnology applications. The paper points out that despite the remarkable progress that has been made, there are still many challenges to the comprehensive understanding and effective treatment of ASD, and interdisciplinary and cross-cultural research and global collaboration are needed to further deepen the understanding of ASD and improve the quality of life of patients.
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Trastorno del Espectro Autista , Humanos , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/terapia , Calidad de Vida , Medicina de Precisión/métodosRESUMEN
T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens, thereby engaging with CD3 on the T cell receptor. This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells. These antibodies have emerged as one of the most promising avenues within tumor immunotherapy. However, despite success in treating hematological malignancies, significant advancements in solid tumors have yet to be explored. In this review, we aim to address the critical challenges associated with T cell-redirecting bispecific antibodies and explore novel strategies to overcome these obstacles, with the ultimate goal of expanding the application of this therapy to include solid tumors.
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â¢Dumping of Fukushima's radioactive wastewater raises marine food web concern.â¢Tritium seems to be the most problematic compound.â¢Long-lived radioisotopes Biomagnify up to 50,000 folds in marine fish species.â¢This threatens fragile deep-sea ecosystems requiring immediate action.â¢Empowered Routine monitoring is crucial to maintain planetary health.
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Chronic hepatitis B (CHB) remains a major public health concern because of the inefficiency of currently approved therapies in clearing the hepatitis B surface antigen (HBsAg). Antibody-based regimens have demonstrated potency regarding virus neutralization and HBsAg clearance. However, high dosages or frequent dosing are required for virologic control. In this study, a dual-domain-engineered anti-hepatitis B virus (HBV) therapeutic antibody 73-DY is developed that exhibits significantly improved efficacy regarding both serum and intrahepatic viral clearance. In HBV-tolerant mice, administration of a single dose of 73-DY at 2 mg kg-1 is sufficient to reduce serum HBsAg by over 3 log10 IU mL-1 and suppress HBsAg to < 100 IU mL-1 for two weeks, demonstrating a dose-lowering advantage of at least tenfold. Furthermore, 10 mg kg-1 of 73-DY sustainably suppressed serum viral levels to undetectable levels for ≈ 2 weeks. Molecular analyses indicate that the improved efficacy exhibited by 73-DY is attributable to the synergy between fragment antigen binding (Fab) and fragment crystallizable (Fc) engineering, which conferred sustained viral suppression and robust viral eradication, respectively. Long-term immunotherapy with reverse chimeric 73-DY facilitated the restoration of anti-HBV immune responses. This study provides a foundation for the development of next-generation antibody-based CHB therapies.
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Antígenos de Superficie de la Hepatitis B , Hepatitis B Crónica , Ratones , Animales , Antígenos de Superficie de la Hepatitis B/análisis , Hepatitis B Crónica/tratamiento farmacológico , Virus de la Hepatitis B , Anticuerpos , FagocitosisRESUMEN
The Qinghai-Tibet Plateau is distinguished by its diverse ecosystems and biodiversity, which are highly dependent on their soil. In this study, a comprehensive analysis was conducted to assess the ecological risks in Maqin County, located on the Qinghai-Tibet Plateau, along with the local background values of soil elements, level of element enrichment, and source appointment of soil elements. The findings show that the background soil element levels in Maqin County were greater than the average soil content values in China. The soils in the study area exhibited pollution levels ranging from weak to moderate. The positive matrix factorization (PMF) model was employed to successfully categorized soil elements into four sources: F1 (natural sources), F2 (grazing sources), F3 (volcanic and rock fracture sources), and F4 (intrusive and deep rock source). Based on the characteristics of the ecological communities and the network environmental analysis model, ecological risks were directly introduced through vegetation and soil microorganisms, with subsequent transmission to other components of the ecosystem through the food chain. The integrated risks associated with vegetation, herbivores, soil microorganisms, and carnivores were 0.0106, 0.00193, 0.0282, and 0.00132, respectively. Notably, soil microorganisms were found to be the primary contributors to the total ecological risk in the study area. Furthermore, network environmental analysis and human health risk models revealed that F1, F2, F3, and F4 accounted for 16.85 %, 8.90 %, 21.76 %, and 52.49 % of the input risk of vegetation and soil microorganisms, respectively. Particularly, F4 emerged as the largest contributor to human health risks. This study provides valuable information for the preservation of the ecological environment in pastoral areas, contributing to the global promotion of sustainable ecological practices.
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Metales Pesados , Contaminantes del Suelo , Humanos , Tibet , Ecosistema , Suelo , Monitoreo del Ambiente , Contaminantes del Suelo/análisis , China , Metales Pesados/análisis , Medición de RiesgoRESUMEN
It is necessary to reveal the responses of the biomass production and metal accumulation capacity of different plants to the variations of atmospheric conditions and soil metals, with the acceleration of urbanization and industrialization. In the present study, a series of experiments were designed to study the individual and interactive influences of O3 and CO2 fumigation on the biomass yield, variation in different leaf types, distribution of cadmium (Cd) in various tissues, and phytoremediation efficiency of Festuca arundinacea using open top chambers. The results found that an elevated O3 content of 80 ppb, a potential O3 content predicted for 2050, decreased the total dry mass of F. arundinacea and increased the proportion of falling leaf tissues of the species significantly. Under the same ambient CO2 levels, O3 fumigation increased the Cd concentrations in the roots and the fresh, mature, senescent, and dead leaf tissues by 27.8%, 133.3%, 94.4%, 125.3%, and 48.6%, respectively. An elevated CO2 content (550 ppm) promoted the biomass yield of F. arundinacea, particularly in the falling leaf tissues. The results of the combined O3 and CO2 treatment showed that CO2 fumigation alleviated the negative effects of O3 on plant growth and increased the accumulation capacity in different plant tissues. Significantly more Cd was accumulated in senescent and dead leaves under the synergistic action of CO2 and O3, suggesting that the phytoremediation effect on F. arundinacea using the falling leaves harvesting method could be improved under the future atmospheric environment of high CO2 and O3 levels.
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Festuca , Ozono , Contaminantes del Suelo , Biodegradación Ambiental , Cadmio/análisis , Dióxido de Carbono , Hojas de la Planta/química , Contaminantes del Suelo/análisisRESUMEN
INTRODUCTION: Triple-negative breast cancer (TNBC) is a subtype of severely aggressive breast cancer that lacks the expression of oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2) and is highly metastatic and related to a poor prognosis. Current standard treatments are still limited to systemic chemotherapy, radiotherapy, and surgical resection. More effective treatments are urgently needed. AREAS COVERED: The immunogenicity of TNBC has provided opportunities for the development of targeted immunotherapy. In this review, we focus on the recent development in antibody-based drug modalities, including angiogenesis inhibitors, immune checkpoint inhibitors, antibody-drug conjugates, immunoconjugates, T cell-redirecting bispecific antibodies and CAR-T cells, and their mechanisms of action in TNBC. EXPERT OPINION: At present, the treatment of TNBC is still a major challenge that needs to be addressed. Novel immunotherapies are promising opportunities for improving the management of this aggressive disease.
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Inmunoconjugados , Neoplasias de la Mama Triple Negativas , Inhibidores de la Angiogénesis , Humanos , Inmunoconjugados/uso terapéutico , Inmunoterapia , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
Currently, modified biochar has been successfully used in the remediation of soil polluted with heavy metals. However, the effects of the modified biochar on pesticides (such as simazine) are still unclear. Herein, the environmental fate of simazine, such as decomposition, leaching, and adsorption in unamended soil, in the soil amended with unmodified and modified biochar (biochar + FeCl3, biochar + FeOS, biochar + Fe) were evaluated. In addition, an incubation experiment was also performed to observe the influence of modified biochar on the microbial community and diversity in the soil. The results showed that modified biochar significantly decreased the decomposition of simazine in the soil compared to its counterpart. Modified biochar also reduced the concentration of simazine in the leachate. Compared with the control, soil microbial biomass in the soil amended with unmodified biochar, biochar + FeCl3, biochar + Fe, and biochar + FeOS was decreased by 5.3%, 18.8%, 8.7%, and 18.1%, respectively. Furthermore, modified biochar changed the structure of the microbial community. This shows that modified biochar could increase the soil adsorption capacity for simazine and change the amount and microbial community that regulates the fate of simazine in the soil. This study concludes that iron-modified biochar has positive and negative effects on the soil. Therefore, its advantages and side effects should be considered before applying it to the soil.