Vertical transmission of SARS-CoV-2 delta-variant in a preterm infant.

BACKGROUND: As SARS-CoV-2 continues to be relevant and cause illnesses, the effect of emerging virus variants on perinatal health remains to be elucidated. It was demonstrated that vertical transmission of SARS-CoV-2 is a relatively rare event in the original SARS-CoV-2 strain. However, very few reports describe vertical transmission related to the delta-variant. CASE PRESENTATION: We report a case of a preterm male neonate born to a mother with positive SARS-CoV-2 and mild respiratory complications. The neonate was born by cesarean section due to fetal distress. The rupture of the amniotic membrane was at delivery. The neonate had expected prematurity-related complications. His nasopharyngeal swabs for RT-PCR were positive from birth till three weeks of age. RT-ddPCR of the Placenta showed a high load of the SARS-CoV-2 virus with subgenomic viral RNA. RNAscope technique demonstrated both the positive strand of the S gene and the orf1ab negative strand. Detection of subgenomic RNA and the orf1ab negative strand indicats active viral replication in the placenta. CONCLUSIONS: Our report demonstrates active viral replication of the SARS-CoV-2 delta-variant in the placenta associated with vertical transmission in a preterm infant.

Unveiling stress-adapted endophytic bacteria: Characterizing plant growth-promoting traits and assessing cross-inoculation effects on Populus deltoides under abiotic stress.

In the face of the formidable environmental challenges precipitated by the ongoing climate change, Plant Growth-Promoting Bacteria (PGPB) are gaining widespread acknowledgement for their potential as biofertilizers, biocontrol agents, and microbial inoculants. However, a knowledge gap pertains to the ability of PGPB to improve stress tolerance in forestry species via cross-inoculation. To address this gap, the current investigation centres on PGPBs, namely, Acinetobacter johnsonii, Cronobacter muytjensii, and Priestia endophytica, selected from the phyllosphere of robust and healthy plants thriving in the face of stress-inducing conditions. These strains were selected based on their demonstrated adaptability to saline, arid, and nitrogen-deficient environments. The utilization of PGPB treatment resulted in an improvement of stomatal conductance (gs) and transpiration rate (E) in poplar plants exposed to both salt and drought stress. It also induced an increase in essential biochemical components such as proline (PRO), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD). These reactions were accompanied by a decrease in leaf malonaldehyde (MDA) content and electrolyte leakage (EL). Furthermore, the PGPB treatment demonstrated a notable enhancement in nutrient absorption, particularly nitrogen and carbon, achieved through the solubilization of nutrients. The estimation of canopy temperature via thermal imaging proved to be an efficient method for distinguishing stress reactions in poplar than conventional temperature recording techniques. In summation, the utilization of PGPB especially Cronobacter muytjensii in this study, yielded profound improvements in the stress tolerance of poplar plants, manifesting in reduced membrane lipid peroxidation, enhanced photosynthesis, and bolstered antioxidant capacity within the leaves.

Analysis of structure-activity and structure-mechanism relationships among thyroid stimulating hormone receptor binding chemicals by leveraging the ToxCast library.

The thyroid stimulating hormone receptor (TSHR) is crucial in thyroid hormone production in humans, and dysregulation in TSHR activation can lead to adverse health effects such as hypothyroidism and Graves' disease. Further, animal studies have shown that binding of endocrine disrupting chemicals (EDCs) with TSHR can lead to developmental toxicity. Hence, several such chemicals have been screened for their adverse physiological effects in human cell lines via high-throughput assays in the ToxCast project. The invaluable data generated by the ToxCast project has enabled the development of toxicity predictors, but they can be limited in their predictive ability due to the heterogeneity in structure-activity relationships among chemicals. Here, we systematically investigated the heterogeneity in structure-activity as well as structure-mechanism relationships among the TSHR binding chemicals from ToxCast. By employing a structure-activity similarity (SAS) map, we identified 79 activity cliffs among 509 chemicals in TSHR agonist dataset and 69 activity cliffs among 650 chemicals in the TSHR antagonist dataset. Further, by using the matched molecular pair (MMP) approach, we find that the resultant activity cliffs (MMP-cliffs) are a subset of activity cliffs identified via the SAS map approach. Subsequently, by leveraging ToxCast mechanism of action (MOA) annotations for chemicals common to both TSHR agonist and TSHR antagonist datasets, we identified 3 chemical pairs as strong MOA-cliffs and 19 chemical pairs as weak MOA-cliffs. In conclusion, the insights from this systematic investigation of the TSHR binding chemicals are likely to inform ongoing efforts towards development of better predictive toxicity models for characterization of the chemical exposome.

In silico identification of potential inhibitors of vital monkeypox virus proteins from FDA approved drugs.

The World Health Organization (WHO) recently declared the monkeypox outbreak 'A public health emergency of international concern'. The monkeypox virus belongs to the same Orthopoxvirus genus as smallpox. Although smallpox drugs are recommended for use against monkeypox, monkeypox-specific drugs are not yet available. Drug repurposing is a viable and efficient approach in the face of such an outbreak. Therefore, we present a computational drug repurposing study to identify the existing approved drugs which can be potential inhibitors of vital monkeypox virus proteins, thymidylate kinase and D9 decapping enzyme. The target protein structures of the monkeypox virus were modelled using the corresponding protein structures in the vaccinia virus. We identified four potential inhibitors namely, Tipranavir, Cefiderocol, Doxorubicin, and Dolutegravir as candidates for repurposing against monkeypox virus from a library of US FDA approved antiviral and antibiotic drugs using molecular docking and molecular dynamics simulations. The main goal of this in silico study is to identify potential inhibitors against monkeypox virus proteins that can be further experimentally validated for the discovery of novel therapeutic agents against monkeypox disease.

Holiday for nature: a way forward in sustainability of the planet.

This paper proposes to observe a day's break as the Planet Day (While the proposed day can also be named as the Gaia Day (after James Lovelock), Planet Day seems to be simpler and easier name for better understanding by the masses and greater connect of the issues with them. Hence, here the proposed day is termed as the Planet Day) every month to allow the nature to heal and ensure sustainability of the planet in the long run. Based on the concept of sustainable degrowth, the paper carries out benefit-cost analysis of the proposed Planet Day and presents a framework based on extensive literature review, secondary data analysis and stakeholders' (Here, participants are referred to as one of the "stakeholders" in the sense that every human being who lives on this planet is accountable for the harm done to it and is impacted by ecological degradation. Hence, they are supposed to contribute to healing of the nature through appropriate initiatives both individually and collectively. In addition to the common residents, there are other stakeholders of the ecology as well such as the government, the business enterprises, and manufacturing firms, etc.) perceptions through a non-random convenience sample survey. The paper finds that the net benefit from the Planet Day amounts to be USD 9002.37 billion across the world and USD 102.48 billion for India per annum. The respondents also perceive the proposed Planet Day as ecologically and economically beneficial and thus support the idea of healing time for the planet. However, a critical challenge is to take different stakeholders on board, ensure their active participation, and design appropriate institutional mechanisms for its successful implementation.

Cheminformatics Analysis of the Multitarget Structure-Activity Landscape of Environmental Chemicals Binding to Human Endocrine Receptors.

In human exposome, environmental chemicals can target and disrupt different endocrine axes, ultimately leading to several endocrine disorders. Such chemicals, termed endocrine disrupting chemicals, can promiscuously bind to different endocrine receptors and lead to varying biological end points. Thus, understanding the complexity of molecule-receptor binding of environmental chemicals can aid in the development of robust toxicity predictors. Toward this, the ToxCast project has generated the largest resource on the chemical-receptor activity data for environmental chemicals that were screened across various endocrine receptors. However, the heterogeneity in the multitarget structure-activity landscape of such chemicals is not yet explored. In this study, we systematically curated the chemicals targeting eight human endocrine receptors, their activity values, and biological end points from the ToxCast chemical library. We employed dual-activity difference and triple-activity difference maps to identify single-, dual-, and triple-target cliffs across different target combinations. We annotated the identified activity cliffs through the matched molecular pair (MMP)-based approach and observed that a small fraction of activity cliffs form MMPs. Further, we structurally classified the activity cliffs and observed that R-group cliffs form the highest fraction among the cliffs identified in various target combinations. Finally, we leveraged the mechanism of action (MOA) annotations to analyze structure-mechanism relationships and identified strong MOA-cliffs and weak MOA-cliffs, for each of the eight endocrine receptors. Overall, insights from this first study analyzing the structure-activity landscape of environmental chemicals targeting multiple human endocrine receptors will likely contribute toward the development of better toxicity prediction models for characterizing the human chemical exposome.

Simulation of the inelastic deformation of porous reservoirs under cyclic loading relevant for underground hydrogen storage.

Subsurface geological formations can be utilized to safely store large-scale (TWh) renewable energy in the form of green gases such as hydrogen. Successful implementation of this technology involves estimating feasible storage sites, including rigorous mechanical safety analyses. Geological formations are often highly heterogeneous and entail complex nonlinear inelastic rock deformation physics when utilized for cyclic energy storage. In this work, we present a novel scalable computational framework to analyse the impact of nonlinear deformation of porous reservoirs under cyclic loading. The proposed methodology includes three different time-dependent nonlinear constitutive models to appropriately describe the behavior of sandstone, shale rock and salt rock. These constitutive models are studied and benchmarked against both numerical and experimental results in the literature. An implicit time-integration scheme is developed to preserve the stability of the simulation. In order to ensure its scalability, the numerical strategy adopts a multiscale finite element formulation, in which coarse scale systems with locally-computed basis functions are constructed and solved. Further, the effect of heterogeneity on the results and estimation of deformation is analyzed. Lastly, the Bergermeer test case-an active Dutch natural gas storage field-is studied to investigate the influence of inelastic deformation on the uplift caused by cyclic injection and production of gas. The present study shows acceptable subsidence predictions in this field-scale test, once the properties of the finite element representative elementary volumes are tuned with the experimental data.

Geomechanical simulation of energy storage in salt formations.

A promising option for storing large-scale quantities of green gases (e.g., hydrogen) is in subsurface rock salt caverns. The mechanical performance of salt caverns utilized for long-term subsurface energy storage plays a significant role in long-term stability and serviceability. However, rock salt undergoes non-linear creep deformation due to long-term loading caused by subsurface storage. Salt caverns have complex geometries and the geological domain surrounding salt caverns has a vast amount of material heterogeneity. To safely store gases in caverns, a thorough analysis of the geological domain becomes crucial. To date, few studies have attempted to analyze the influence of geometrical and material heterogeneity on the state of stress in salt caverns subjected to long-term loading. In this work, we present a rigorous and systematic modeling study to quantify the impact of heterogeneity on the deformation of salt caverns and quantify the state of stress around the caverns. A 2D finite element simulator was developed to consistently account for the non-linear creep deformation and also to model tertiary creep. The computational scheme was benchmarked with the already existing experimental study. The impact of cyclic loading on the cavern was studied considering maximum and minimum pressure that depends on lithostatic pressure. The influence of geometric heterogeneity such as irregularly-shaped caverns and material heterogeneity, which involves different elastic and creep properties of the different materials in the geological domain, is rigorously studied and quantified. Moreover, multi-cavern simulations are conducted to investigate the influence of a cavern on the adjacent caverns. An elaborate sensitivity analysis of parameters involved with creep and damage constitutive laws is performed to understand the influence of creep and damage on deformation and stress evolution around the salt cavern configurations. The simulator developed in this work is publicly available at https://gitlab.tudelft.nl/ADMIRE_Public/Salt_Cavern .

Analysis of COVID-19 cases and associated ventilator requirement in Indian States

Analysis of COVID-19 cases and prediction of quantity of associated ventilator requirement is very relevant during this pandemic. This paper presents a method for predictive estimation of ventilator requirement for COVID-19 patients in Indian states. It uses ARIMA (Autoregressive Integrated Moving Average) model for predicting the future cumulative cases and daily fatality. Taking cue from this, ventilator requirement is estimated for each state. State wise estimation of ventilator is important because public healthcare system in India is managed at state level. Dataset on Novel Corona Disease 2019 in India from Kaggle website is used in this work.

Enhanced endothelial delivery and biochemical effects of α-galactosidase by ICAM-1-targeted nanocarriers for Fabry disease.

Fabry disease, due to the deficiency of α-galactosidase A (α-Gal), causes lysosomal accumulation of globotriaosylceramide (Gb3) in multiple tissues and prominently in the vascular endothelium. Although enzyme replacement therapy (ERT) by injection of recombinant α-Gal improves the disease outcome, the effects on the vasculopathy associated with life-threatening cerebrovascular, cardiac and renal complications are still limited. We designed a strategy to enhance the delivery of α-Gal to organs and endothelial cells (ECs). We targeted α-Gal to intercellular adhesion molecule 1 (ICAM-1), a protein expressed on ECs throughout the vasculature, by loading this enzyme on nanocarriers coated with anti-ICAM (anti-ICAM/α-Gal NCs). In vitro radioisotope tracing showed efficient loading of α-Gal on anti-ICAM NCs, stability of this formulation under storage and in model physiological fluids, and enzyme release in response to lysosome environmental conditions. In mice, the delivery of (125)I-α-Gal was markedly enhanced by anti-ICAM/(125)I-α-Gal NCs in brain, kidney, heart, liver, lung, and spleen, and transmission electron microscopy showed anti-ICAM/α-Gal NCs attached to and internalized into the vascular endothelium. Fluorescence microscopy proved targeting, endocytosis and lysosomal transport of anti-ICAM/α-Gal NCs in macro- and micro-vascular ECs and a marked enhancement of Gb3 degradation. Therefore, this ICAM-1-targeting strategy may help improve the efficacy of therapeutic enzymes for Fabry disease.

Impact of anaerobically treated and untreated (raw) distillery effluent irrigation on soil microflora, growth, total chlorophyll and protein contents of Phaseolus aureus L.

Impact of distillery effluent (untreated and treated) irrigation on soil microflora of the pots used for growing Phaseolus aureus L. was investigated. The growth of the P. aureus plants as affected by distillery effluent irrigation was also evaluated. The irrigation of the pots by 1-10% distillery effluent (anaerobically treated) stimulated the growth of the soil microflora (increased number of bacteria, fungi and actinomycetes) and P. aureus plants (increased shoot and root lengths, biomass, chlorophyll and protein contents). Further, 15-20% distillery effluent (anaerobically treated) had toxic effect on soil micro flora as indicated by reduced number of bacteria, fungi and actinomycetes. Reduction in shoot, root, lengths, biomass, chlorophyll, protein contents of P. aureus was also observed when irrigated by 15-20% treated distillery effluent. All the concentrations of raw distillery effluent reduced the bacterial population. However, the treated distillery effluent concentrations <10% had stimulatory effect on fungal and actinomycetes population. However, raw effluent concentrations >5% reduced the same. Raw distillery effluent was more toxic to P. aureus than treated distillery effluent as concentrations >5%, had reduced the growth (shoot, root length and biomass) of the test plant. Raw distillery effluent had adverse effect to total chlorophyll contents and all the test concentrations reduced the total chlorophyll level. However, untreated (raw) distillery effluent stimulated the protein content initially. It has been concluded from-present study that lower concentrations of the raw distillery effluent (1-5%) and treated distillery effluent (1-10%) had stimulated the growth of P. aureus and soil microflora except soil bacteria (inhibited by all the concentration of the raw effluent). However, higher concentrations (raw effluent: 10-20%; treated effluent 15-20%) had toxicity to test parameters.