Entry pathways determined the effects of MPs on sludge anaerobic digestion system: The views of methane production and antibiotic resistance genes fates.

Sludge is one of the primary reservoirs of microplastics (MPs), and the effects of MPs on subsequent sludge treatment raised attention. Given the entry pathways, MPs would exhibit different properties, but the entry pathway-dependent effect of MPs on sludge treatment performance and the fates of antibiotic resistance genes (ARGs), another high-risk emerging contaminant, were seldom documented. Herein, MPs with two predominant entry pathways, including wastewater-derived (WW-derived) and anaerobic digestion-introduced (AD-introduced), were used to investigate the effects on AD performance and ARGs abundances. The results indicated that WW-derived MPs, namely the MPs accumulated in sludge during the wastewater treatment process, exhibited significant inhibition on methane production by 22.8%-71.6%, while the AD-introduced MPs, being introduced in the sludge AD process, slightly increased the methane yield by 4.7%-17.1%. Meanwhile, MPs were responsible for promoting transmission of target ARGs, and polyethylene terephthalate MPs (PET-MPs) showed a greater promotion effect (0.0154-0.0936) than polyamide MPs (PA-MPs) (0.0013-0.0724). Compared to size, entry pathways and types played more vital roles on MPs influences. Investigation on mechanisms based on microbial community structure revealed characteristics (aging degree and types) of MPs determined the differences of AD performance and ARGs fates. WW-derived MPs with longer aging period and higher aging degree would release toxics and decrease the activities of microorganisms, resulting in the negative impact on AD performance. However, AD-introduced MPs with short aging period exhibited marginal impacts on AD performance. Furthermore, the co-occurrent network analysis suggested that the variations of potential host bacteria induced by MPs with different types and aging degree attributed to the dissemination of ARGs. Distinctively from most previous studies, the MPs with different sizes did not show remarkable effects on AD performance and ARGs fates. Our findings benefited the understanding of realistic environmental behavior and effect of MPs with different sources.

[Molecular basis of biological activity of polysaccharides in COVID-19 associated conditions]. / Molekuliarnye osnovy biologicheskoi aktivnosti polisakharidov pri assotsiirovannykh s COVID-19 sostoianiiakh.

The review considers the main molecular biological features of the COVID-19 causative agent, the SARS-CoV-2 virus: life cycle, viral cell penetration strategies, interactions of viral proteins with human proteins, cytopathic effects. We also analyze pathological conditions that occur both during the course of the COVID-19 disease and after virus elimination. A brief review of the biological activities of polysaccharides isolated from various sources is given, and possible molecular biological mechanisms of these activities are considered. Data analysis shows that polysaccharides are a class of biological molecules with wide potential for use in the treatment of both acute conditions in COVID-19 and post-COVID syndrome.

Characterization of Entry Pathways, Species-Specific Angiotensin-Converting Enzyme 2 Residues Determining Entry, and Antibody Neutralization Evasion of Omicron BA.1, BA.1.1, BA.2, and BA.3 Variants.

The SARS-CoV-2 Omicron variants were first detected in November 2021, and several Omicron lineages (BA.1, BA.2, BA.3, BA.4, and BA.5) have since rapidly emerged. Studies characterizing the mechanisms of Omicron variant infection and sensitivity to neutralizing antibodies induced upon vaccination are ongoing by several groups. In the present study, we used pseudoviruses to show that the transmembrane serine protease 2 (TMPRSS2) enhances infection of BA.1, BA.1.1, BA.2, and BA.3 Omicron variants to a lesser extent than ancestral D614G. We further show that Omicron variants have higher sensitivity to inhibition by soluble angiotensin-converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G. The Omicron variants also more efficiently used ACE2 receptors from 9 out of 10 animal species tested, and unlike the D614G variant, used mouse ACE2 due to the Q493R and Q498R spike substitutions. Finally, neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7- to 8-fold less potent than the D614G. These results provide insights into the transmissibility and immune evasion capacity of the emerging Omicron variants to curb their ongoing spread. IMPORTANCE The ongoing emergence of SARS-CoV-2 Omicron variants with an extensive number of spike mutations poses a significant public health and zoonotic concern due to enhanced transmission fitness and escape from neutralizing antibodies. We studied three Omicron lineage variants (BA.1, BA.2, and BA.3) and found that transmembrane serine protease 2 has less influence on Omicron entry into cells than on D614G, and Omicron exhibits greater sensitivity to endosomal entry inhibition compared to D614G. In addition, Omicron displays more efficient usage of diverse animal species ACE2 receptors than D614G. Furthermore, due to Q493R/Q498R substitutions in spike, Omicron, but not D614G, can use the mouse ACE2 receptor. Finally, three doses of Pfizer/BNT162b2 mRNA vaccination elicit high neutralization titers against Omicron variants, although the neutralization titers are still 7- to 8-fold lower those that against D614G. These results may give insights into the transmissibility and immune evasion capacity of the emerging Omicron variants to curb their ongoing spread.

Improving access to drug and alcohol treatment in NSW Australia: The role of self-determination and peer support.

One of the key issues in the alcohol and other drug (AOD) treatment sector concerns the reported difficulties that clients have in accessing treatment. This paper draws on qualitative interview data collected from clients undergoing treatment (n = 20) and stakeholders (n = 15) of five specialist non-government AOD treatment services in New South Wales, Australia, to offer an in-depth perspective about treatment entry experiences. We identified four key themes of positive treatment entry experiences: the presence of high-quality online information which enabled clients to best match themselves to treatment; flexible and simple intake procedures with skilled and welcoming staff; the presence and quality of social and other resources (such as families, peers and private health insurance) which enabled quicker access; and prior experience in the treatment system which helped clients to gain important knowledge and skills to improve future access. We discuss implications of these findings, including that waiting lists significantly exacerbate inequity, but that this could be ameliorated by providing peer-support to those trying to gain entry, especially clients who do not have family and friends for help during this period. The findings also point to the way that client self-determination is central to all positive treatment entry experiences, and that supporting clients to find 'the right fit' in relation to treatment options improves their experiences.

Multiple pesticides in lentic small water bodies: Exposure, ecotoxicological risk, and contamination origin.

Lentic small water bodies (LSWB) are a highly valuable landscape element with important ecosystem services and benefits for humans and the environment. However, data about their pesticide contamination dynamic and the associated ecotoxicological effects are scarce. To overcome these knowledge gaps, five LSWBs located in agricultural fields in Northern Germany were studied during the spring pesticide application period (April to July 2018) and the concentrations of 94 pesticides were measured in weekly intervals. The goals of this study were to observe the trends of pesticide contamination during the application period, assess the ecotoxicity of the contamination, and assign the findings to temporal and spatial origins. Samples contained pesticide concentrations between 0.12 and 4.83 µg L-1 as sums. High detection frequencies (81% of samples) and concentrations (max 1.2 µg L-1) were observed for metazachlor transformation products. Contamination from multiple pesticides was detected with up to 25 compounds per sample and a maximum of 37 compounds per LSWB during the entire sampling period. High toxicities for algae and macrophytes were recorded using toxic units (TU) of -0.2 to -3.5. TUs for invertebrates were generally lower than for algae/macrophytes (-2.7 to -5.2) but were also recorded at levels with ecological impacts. Pesticide detections were separated into four categories to assign them to different temporal and spatial origins. Pesticides from the spring (5-11%) and the previous autumn (0-36%) application periods were detected in the LSWB. Some pesticides could be related to the application of the previous crop on the same field (0-39%), but most of the compounds (44-85%) were not related to the crop management in the last two years on the respective LSWB fields. The relevance of different input pathways is still unknown. Particularly, the effect of long-distance transport needs to be clarified to protect aquatic biota in LSWBs.

Combating sars-cov-2 through lipoxins, proteasome, caveolin and nuclear factor-κb pathways in non-pregnant and pregnant populations.

It can be misleading to think that the new severe acute respiratory syndrome coronavirus (SARS-CoV2) which has a very strong mutation and adaptation capabilities, uses only the angiotensin-converting enzyme II (ACE2) pathway to reach target cells. Despite all the precautions taken, the pandemic attack continues and the rapid increase in the number of deaths suggest that this virus has entered the cell through different pathways and caused damage through different mechanisms. The main reason why the ACE2 pathway comes to the fore in all scientific studies is that this receptor is located at the entry point of basic mechanisms that provide alveolo-capillary homeostasis. SARS-CoV-2 has to use nuclear factor-κB (NF-kB), caveloae, clathrin, lipoxin, serine protease and proteasome pathways in addition to ACE2 to enter the target cell and initiate damage. For this reason, while new drug development studies are continuing, in order to be beneficial to patients in their acute period, it is imperative that we are able to come up with drugs that activate or inhibit these pathways and are currently in clinical use. It is also critical that we adopt these new pathways to the treatment of pregnant women affected by SARS-CoV-2, based on the scientific data we use to treat the general population.