Interactive adverse effects of low-density polyethylene microplastics on marine microalga Chaetoceros calcitrans.

Low-density polyethylene (LDPE) is broadly utilized worldwide, increasing more dramatically during the COVID-19 pandemic, and the majority ends up in the aquatic environment as microplastics. The influence of polyethylene microplastics (LDPE-MPs) on aquatic ecosystems still needs further investigation, especially on microalgae as typical organisms represented in all aquatic systems and at the base of the trophic chain. Thereby, the biological and toxicity impacts of LDPE-MPs on Chaetoceros calcitrans were examined in this work. The results revealed that LDPE-MPs had a concentration-dependent adverse effect on the growth and performance of C. calcitrans. LDPE-MPs contributed the maximum inhibition rates of 85%, 51.3%, 21.49% and 16.13% on algal growth chlorophyll content, φPSII and Fv/Fm, respectively. The total protein content, superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activities were significantly increased at 25 mg L-1 LDPE-MPs by 1.37, 3.52, 2.75 and 1.84 folds higher than those of the controls to sustain the adverse effects of LDPE-MPs. Extracellular polymeric substance (EPS) and monosaccharides contents of C. calcitrans were improved under low concentration of LDPE-MPs, which could facilitate the adsorption of MPs particles on the microalgae cell wall. This adsorption caused significant physical damage to the algal cell structure, as observed by SEM. These results suggest that the ecological footprint of MPs may require more attention, particularly due to the continuing breakdown of plastics in the ecosystem.

Weathering and degradation of polylactic acid masks in a simulated environment in the context of the COVID-19 pandemic and their effects on the growth of winter grazing ryegrass.

The COVID-19 pandemic has led to explosive growth in the production and consumption of disposable medical masks, which has caused new global environmental problems due to the improper disposal of these masks and lack of effective mask recycling methods. To reduce the environmental load caused by the inability of synthetic plastics to degrade, polylactic acid (PLA) masks, as a biodegradable environmentally friendly plastic, may become a solution. This study simulated the actual degradation process of new PLA masks in different environments by soaking them in various solutions for 4 weeks and explored the influence of the treated PLA fabric fibers on the growth of winter ryegrass. The results show that the weathering degradation of PLA fibers in water mainly occurs through the hydrolysis of ester bonds, and weathering leads to cheese-like and gully-like erosion on the surface of the PLA fiber fabric layer and finally to fiber fracture and the release of microplastics (MPs). The average number of MPs released within 4 weeks is 149.5 items/piece, the particle size is 20-500 µm (44%), and 63.57% of the MPs are transparent fibers. The outer, middle, and inner layers of weathered PLA masks tend to be hydrophilic and have lower mechanical strength. PLA fibers after different treatment methods affect the growth of winter ryegrass. PLA masks are undoubtedly a greener choice than ordinary commercial masks, but in order to confirm this, the entire degradation process, the final products, and the impact on the environment need to be further studied. In the future, masks may be developed to be made from more environmentally friendly biodegradable materials that can have good protecting effects and also solve the problem of end-of-life recycling. A SYNOPSIS: Simulation of the actual degradation process of PLA masks and exploration of the influence of mask degradation on the growth of winter ryegrass.

Infiltracao Medular Por Leucemia Mieloide Aguda (Lma) E Tumor Solido (Ts) Metastatico: Relato De Caso

Objetivo: Descrever um caso com duas neoplasias concomitantes infiltrando medula ossea (MO), sendo uma delas hematologica e outra, TS. Material e metodos: Relato de caso por meio de coleta de dados de prontuario de paciente acompanhado no HAC. Resultados: Paciente 67 anos, masculino, tabagista (100 anos/maco), ex-etilista, historia de inalacao de tintas com benzeno (pintor de carros por 30 anos), com astenia e anemia ha 4 meses, associado a perda de 25kg. Procurou atendimento em marco/22 com diagnostico de COVID-19 e necessidade de internacao hospitalar. Evoluiu com bicitopenia sendo transferido ao HAC para investigacao. Ao exame fisico: ECOG 3. Hemograma: bicitopenia (Hb 5.8 mg/dL;plaquetas 40000/mm3;leucocitos 13000/mm3;69% blastos). TC: derrame pleural a direita;raros micronodulos pulmonares;enfisema pulmonar difuso acentuado com areas de fibrose associadas;linfonodomegalias mediastinais e hilares, lesoes osteoliticas esparsas. Mielograma: dispoese das tres linhagens, com 24% de celulas blasticas, alem de grumos de celulas nao-hematologicas (TS). Em Citometria de Fluxo (Euroflow): 16% de mieloblastos patologicos, expressando CD7, CD13, CD33, CD34, CD38, CD44, CD71, CD97, CD123. Citogenetica: 47,XY,+8. Nao foi realizada avaliacao molecular. Biopsia de MO: infiltracao macica da medula ossea por tumor solido. Imunohistoquimica com positividade para: CK7 e TTF-1 e negatividade para: CK20, PSA, PAX-8, CD10, CDX-2, GATA-3. Diagnostico final: infiltracao da MO por adenocarcinoma, favorecido sitio pulmonar, e em area residual, infiltracao por Leucemia mieloide aguda, com alteracao citogenetica associada a mielodisplasia (ELN 2022). Como tratava-se de idoso fragil, sem possibilidade de tratamento intensivo das doencas leucemica e oncologica, proposto tratamento paliativo exclusivo, com medidas de suporte. Paciente faleceu apos 2 meses do diagnostico. Discussao: A associacao de LMA com TS nao e rara. O risco de um paciente previamente tratado para TS desenvolver LMA pode ser ate 10 vezes maior que a populacao normal. Relatos de casos de TS recidivados em MO e LMA concomitantes foram descritos, com desfechos sombrios. Contudo, nao ha na literatura a descricao de LMA de novo com TS infiltrando MO concomitantes ao diagnostico. Estudo chines de 2020, analisou 12 casos de LMA associada a TS primario sincronicos, sendo: 3 etiologia pulmonar, 1 mama, 1 mola, e 7 com neoplasia de TGI. O intervalo de tempo mediano para o diagnostico das duas neoplasias foi de 4 meses. O tratamento da LMA foi realizado com quimioterapia (QT) de alta intensidade ou agente hipometilante. A sobrevida global mediana foi de 12.5 meses (porem somente 4/12 tinham TS avancado). Um estudo americano em 2009 analisou 5 pacientes com LMA e tumor de pulmao (2 com doenca avancada) sincronicos. Todos foram tratados com QT de alta intensidade, e a sobrevida media foi de 5 meses (3-21). Conclusao: Este e o primeiro relato de caso de LMA e TS metastatico infiltrando MO concomitantemente ao diagnostico. A LMA deve ser tratada prioritariamente por ser doenca altamente agressiva, levando-se em conta as condicoes clinicas do paciente, com avaliacao individual. E mesmo com tratamento intensivo, o prognostico e reservado. Copyright © 2022

Antibacterial and Phagocytic Properties of a Novel Silver-Interferon Complex

Background: Developing new antibacterial and antiviral drugs are considered a significant issue due to the emergence and spread of resistant strains of microorganisms. The COVID-19 pandemic has dramatically increased the need for new broad-spectrum anti-infective agents. Objective(s): This experimental study aimed to investigate the antibacterial and phagocytic properties of silver-interferon preparation. The combination of properties of complex drugs makes them promising for treating drug-resistant infections and bacterial complications of viral diseases. Method(s): The antibacterial effect of the silver-interferon platform was investigated by agar diffusion and serial dilution methods. The drug's effect on the functional activity of phagocytes was studied on human neutrophils in a Staphylococcus aureus uptake test. Result(s): Investigations have shown that the silver-interferon complex possesses a bactericidal mechanism of action against tested bacterial strains, including Streptococcus pneumonia, Salmonella enteritidis, Staphylococcus aureus, Escherichia coli. Streptococcus pneumonia was the most susceptible bacterial target for the tested complex, with a growth inhibition zone of 12+/-0.6 mm and a minimal bactericidal concentration of 0.08 mg/ml. A slight stimulating action of the drug in relation to the activity of phagocytes was revealed. Conclusion(s): Silver-interferon has proved as a prospective anti-infective drug with a wide range of activities. Copyright © 2022 Bentham Science Publishers.

A Whole-Body Quantitative System Pharmacology Physiologically-Based Pharmacokinetic (QSP/PBPK) Model to Support Dose Selection of ADG20: An Extended Half-Life Monoclonal Antibody Being Developed for the Treatment of Coronavirus Disease (COVID-19)

Background. ADG20 is a fully human IgG1 monoclonal antibody engineered to have potent and broad neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other SARS-like CoVs with pandemic potential and an extended half-life. ADG20 is administered intramuscularly (IM). A QSP/PBPK model was constructed to support dose selection for a Phase 2/3 trial of ambulatory patients with mild to moderate COVID-19 (STAMP: NCT04805671). Methods. A QSP/PBPK model was used to simulate receptor occupancy (RO) and drug exposure in the upper airway (nasopharyngeal/oropharyngeal epithelial lining fluid [ELF] compartment). RO was linked to an existing viral dynamic model to enable the prediction of the natural time course of viral load and the effect of ADG20 on viral clearance and infectivity rate. RO was calculated using: 1) in vitro ADG20-SARS-CoV-2 binding kinetics (association rate constant (kon) of 1.52E+06 M-1•s1 and dissociation rate constant (koff) of 2.81E-04 s-1 from a Biacore assay;2) time course of ADG20 concentrations in ELF;and 3) time course of viral load following ADG20 administration. Molar SARS-CoV-2 viral binding site capacity was calculated assuming 40 spike proteins per virion, 3 binding sites per spike, and an initial viral load of log 107 copies/mL for all patients. The QSP/PBPK model and a 2018 CDC reference body weight distribution (45-150 kg) were used to simulate 1000 concentration-time profiles for a range of candidate ADG20 regimens. ADG20 regimens were evaluated against 2 criteria: 1) ability to attain near complete ( >90%), and durable (28-day) SARS-CoV-2 RO in the ELF;and 2) ability to maintain ELF ADG20 concentrations relative to a concentration (0.5 mg/L) associated with 100% viral growth suppression in an in vitro post-infection assay. Results. A single 300 mg IM ADG20 dose met the dose selection criteria in terms of RO (Figure A) and viral growth suppression (Figure B). Conclusion. These data support the evaluation of an ADG20 300 mg IM dose for the treatment of mild to moderate COVID-19. ADG20 is forecasted to attain near complete ( >90%) SARS-CoV-2 RO in the ELF and maintain ELF ADG20 concentrations above that associated with 100% viral growth suppression in vitro.

Phytotoxicity assessment of biodegradable and non-biodegradable plastics using seed germination and early growth tests.

Global production of plastics remains at the high level despite the SARS-Cov-2 pandemic. These are primarily petroleum-derived plastics but the contribution of bio-based plastics estimated at the level of 1% in the plastic market in 2019 is expected to be increasing. Simultaneously, the significant part of plastic waste is still disposed improperly and pollutes the environment making a threat to all living organisms. In this work three plastic materials, two bio-based biodegradable: polylactide (PLA) and polyhydroxybutyrate (PHB), and one petroleum-derived non-biodegradable polypropylene (PP) were studied towards their effects on seed germination and early growth of higher plants. The following plants were used as bioindicators: monocotyledonous plant - Sorghum saccharatum and two dicotyledonous plants: Sinapsis alba and Lepidium sativum. Plastics did not affect seed germination of higher plants even at the highest concentration tested (11.9% w/w) but their presence in soil acted in various ways on growth of the plants. Either no or inhibitive or stimulation effects on growth of roots or stems were noticed. It depended on the concentration and chemical composition of the plastic tested, and plant species. PHB and PLA more often caused to the inhibition of root growth than PP did. This phenomenon was observed in particular with regard to the dicotyledonous plants. Moreover, in the tests with the dicotyledonous plants (S. alba and L. sativum) the dose-response relations were usually determined as statistically relevant. Among these plants cress (L. sativum) occurred to be more sensitive and allowed for obtaining the dose-response dependence for both root and stem length, and, what is important, it took place in the case of each of materials tested. Therefore, cress is recommended to be used as a bioindicator in the assessment of the effect of plastics (petroleum-derived and bio-based plastics) on the early stages of growth of higher plants.

Development of ciclesonide analogues that block SARS-CoV-2 RNA replication.

Ciclesonide is an inhaled corticosteroid used to treat asthma and is currently undergoing clinical trials for treatment of coronavirus disease 2019 (COVID-19). An active metabolite of ciclesonide, Cic2, was recently reported to repress severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomic RNA replication. Herein, we designed and synthesized a few types of ciclesonide analogues. Cic4 (bearing an azide group) and Cic6 (bearing a chloro group) potently decreased SARS-CoV-2 viral replication and had low cytotoxicity compared with Cic2 (bearing a hydroxy group). These compounds are promising as novel therapeutic agents for COVID-19 that show significant antiviral activity.