Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. ...Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs. We describe three different platform designs - "4-way", "7-way", and "10-way" - each accommodating a mixing chamber and up to 4, 7, or 10 MPSs. Platforms accommodate multiple different MPS flow configurations, each with internal re-circulation to enhance molecular exchange, and feature on-board pneumatically-driven pumps with independently programmable flow rates to provide precise control over both intra- and inter-MPS flow partitioning and drug distribution. We first developed a 4-MPS system, showing accurate prediction of secreted liver protein distribution and 2-week maintenance of phenotypic markers. We then developed 7-MPS and 10-MPS platforms, demonstrating reliable, robust operation and maintenance of MPS phenotypic function for 3 weeks (7-way) and 4 weeks (10-way) of continuous interaction, as well as PK analysis of diclofenac metabolism. This study illustrates several generalizable design and operational principles for implementing multi-MPS "physiome-on-a-chip" approaches in drug discovery.
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•Non- conventional, biogenic method for fabricating magnetite-biochar-nanocomposite.•Adsorption capacity for phosphate=7.95mg/g and nitrates=5.26mg/g.•99% and 96% phosphate removal ...from batch synthetic water and column real wastewater.•High nutrient recovery ensures use of spent adsorbent as soil amendment.•Better selectivity, regenerability and separability ensure advanced adsorbent.
Presence of nutrients in municipal sewage water in high concentrations has raised awareness of their reuse as a vital limiting resource. With an aim to recover the nutrients in a form that can be used as a soil amendment, a novel biocompatible nanocomposite (BC-P@MNP) was fabricated using green methods. Polysaccharide induced biogenic magnetite nanoparticles (P@MNP) were immobilized onto the biochar of jackfruit peel (BC) to fabricate BC-P@MNP. Microwave irradiation employed during the fabrication of BC-P@MNP involved less energy consumption, high yields and better adsorption performance as compared to BC and other reported biochar-composites. Structural features like mesoporosity, crystallinity, magnetism, functionality and nano-sized dimension was demonstrated in BC-P@MNP. Under optimized conditions, batch studies revealed a maximum adsorption efficiency of 7.94mg/g and 5.26mg/g for phosphates and nitrates respectively. Thermodynamics revealed the feasibility and exothermicity of the system. The high selectivity in the presence of competing co-anions, high regeneration capacity and better separability enable BC-P@MNP to be used as advanced, economical adsorbent for wastewater applications. High nutrient recovery and biocompatibility ensured the potential of the spent adsorbent to be used as a soil amendment. Breakthrough curves obtained from fixed-bed column tests conducted on agricultural wastewater demonstrated the use of higher bed depths and lower flow rates for achieving higher phosphate removal as well as for ensuring lower unused column bed. The study demonstrated the technological advancement of a biogenic nanocomposite fabricated from green methods over other reported adsorbents for removal and recovery of nutrients from water.
Abstract
Radiological imaging is extremely valuable as a diagnostic tool in the pediatric population, but it comes with a number of distinct challenges as compared to the imaging of adults. This is ...because of the following: It requires dedicated imaging protocols to acquire the images, there is need for sedation or general anesthesia for longer procedures such as MRI, specific training is required for the healthcare personnel involved, thorough knowledge and expertise should be applied for evaluating the images, and most importantly, it requires consideration for radiation exposure if ionizing radiation is being used. One of the challenges for clinical care personnel is to gain the child's trust and co-operation before and throughout the duration of an examination, which can prove to be difficult in children who may be ill and have pain. This is important to acquire quality images and prevent repeat examinations. Even with a quality examination, the accurate interpretation of images requires a thorough knowledge of the intricate and dynamic face of anatomy and specific pathological presentations in children. The increased radiation sensitivity of growing organs and children's longer expected life spans make them more susceptible to the harmful effects of radiation. Imaging pediatric patients in a dedicated pediatric imaging department with dedicated pediatric CT technologists may result in greater compliance with pediatric protocols and significantly reduced patient dose. In order to prevent the harmful effects of ionizing radiation, As Low As Reasonably Achievable (ALARA) principle should be strictly followed. This article seeks to draw attention to various challenges of pediatric imaging and the ways to overcome them.
Ship voyage to Antarctica is a stressful journey for expedition members. The response of human gut microbiota to ship voyage and a feasible approach to maintain gut health, is still unexplored. The ...present findings describe a 24-day long longitudinal study involving 19 members from 38th Indian Antarctic Expedition, to investigate the impact of ship voyage and effect of probiotic intervention on gut microbiota. Fecal samples collected on day 0 as baseline and at the end of ship voyage (day 24), were analyzed using whole genome shotgun sequencing. Probiotic intervention reduced the sea sickness by 10% compared to 44% in placebo group. The gut microbiome in placebo group members on day 0 and day 24, indicated significant alteration compared to a marginal change in the microbial composition in probiotic group. Functional analysis revealed significant alterations in carbohydrate and amino acid metabolism. Carbohydrate-active enzymes analysis represented functional genes involved in glycoside hydrolases, glycosyltransferases and carbohydrate binding modules, for maintaining gut microbiome homeostasis. Suggesting thereby the possible mechanism of probiotic in stabilizing and restoring gut microflora during stressful ship journey. The present study is first of its kind, providing a feasible approach for protecting gut health during Antarctic expedition involving ship voyage.
The various strains and mutations of SARS-CoV-2 have been tracked using several forms of genomic classification systems. The present study reports high-throughput sequencing and analysis of 99 ...SARS-CoV-2 specimens from Western Uttar Pradesh using sequences obtained from the GISAID database, followed by phylogeny and clade classification. Phylogenetic analysis revealed that Omicron lineages BA-2-like (55.55%) followed by Delta lineage-B.1.617.2 (45.5%) were predominantly circulating in this area Signature substitution at positions S: N501Y, S: D614G, S: T478K, S: K417N, S: E484A, S: P681H, and S: S477N were commonly detected in the Omicron variant-BA-2-like, however S: D614G, S: L452R, S: P681R and S: D950N were confined to Delta variant-B.1.617.2. We have also identified three escape variants in the S gene at codon position 19 (T19I/R), 484 (E484A/Q), and 681 (P681R/H) during the fourth and fifth waves in India. Based on the phylogenetic diversification studies and similar changes in other lineages, our analysis revealed indications of convergent evolution as the virus adjusts to the shifting immunological profile of its human host. To the best of our knowledge, this study is an approach to comprehensively map the circulating SARS-CoV-2 strains from Western Uttar Pradesh using an integrated approach of whole genome sequencing and phylogenetic analysis. These findings will be extremely valuable in developing a structured approach toward pandemic preparedness and evidence-based intervention plans in the future.
The study acclaims the generation of hard, wear-resistant, and lubricating layer on Ti alloy using molybdenum disulfide (MoS
2
) powders mixed in dielectric (deionized water) using a brass tool ...electrode (diameter 800 μm) through the micro-electrical discharge process. The deposition rate, micro-hardness, recast layer, and surface roughness were studied for the surface generated through the process and correlated with the XRD, AFM, electron probe micro-analyzer, EDS analysis, and FESEM images. Results indicate that a higher voltage (60 V) and powder concentration (12 g/L) increase the material deposition rate in the form of intermetallic compounds deposited on the recast layer. The coated layer formed shows an increase in micro-hardness ranging from 426.42 to 714.25 HV, which is more when compared to the base material hardness of 417.61 HV. In addition to this, lower micro-cracks were seen at high powder concentration, voltage, and duty factor with improved surface quality. The pin-on-disc wear test of the coated samples was performed, and results indicated that the specific wear rate decreased with the increase in duty factor due to the formation of hard and wear-resistant intermetallic compounds as confirmed from the EDS and XRD plots.
On-platform pumping systems are a potentially critical technology for microphysiological systems (MPS) to control the pressure and flow of growth media. Supporting sufficient physiological tissue ...quantity in culture requires fluid flow rates on the order of microliters per second, which is larger than for typical microfluidic systems. Thus, a need exists for new types of pumping systems operating in this flow range while maintaining stringent sterility of the culture as well as enabling tight temperature control at <inline-formula><tex-math notation="LaTeX">{37}^{\circ } {\rm C}</tex-math></inline-formula>. Flow rates and pressure also need to be readily computer-controlled, with a manageable set of connections into the culture incubator environment. This article describes a novel mesoscale electromagnetically driven pumping system designed to meet all these requirements. Our design achieves a very low energy dissipation of <inline-formula><tex-math notation="LaTeX">{0.65}\,{\rm mJ}</tex-math></inline-formula> per switching event, which allows one pumping channel to operate at <inline-formula><tex-math notation="LaTeX">{0.45}\,{{\rm {\mu } L} /{\rm s}}</tex-math></inline-formula> with an average power dissipation of 1.3 mW and <inline-formula><tex-math notation="LaTeX">{0.04}\,{{^\circ } {\rm C}}</tex-math></inline-formula> temperature rise in each actuator. The actuator operates in a bistable, teeter-totter configuration with a latching force of <inline-formula><tex-math notation="LaTeX">{4.5}\,{\rm N}</tex-math></inline-formula>, and a relatively large stroke of <inline-formula><tex-math notation="LaTeX">{400}\,{{\mu } {\rm m}}</tex-math></inline-formula> at the actuator pole face. Preliminary operational pumping test results show the potential of this type of electromagnetic actuator for fluidic pumping. Due to their compact configuration and very high energy efficiency, these pumps can provide the foundation for multichannel, on-platform pumping for MPS platforms, as well as for a range of sterile, temperature-sensitive microflow devices such as portable, battery-operated insulin pumps.
Although the therapeutic efficacy and commercial success of monoclonal antibodies (mAbs) are tremendous, the design and discovery of new candidates remain a time and cost-intensive endeavor. In this ...regard, progress in the generation of data describing antigen binding and developability, computational methodology, and artificial intelligence may pave the way for a new era of in silico on-demand immunotherapeutics design and discovery. Here, we argue that the main necessary machine learning (ML) components for an in silico mAb sequence generator are: understanding of the rules of mAb-antigen binding, capacity to modularly combine mAb design parameters, and algorithms for unconstrained parameter-driven in silico mAb sequence synthesis. We review the current progress toward the realization of these necessary components and discuss the challenges that must be overcome to allow the on-demand ML-based discovery and design of fit-for-purpose mAb therapeutic candidates.
The WHO announced coronavirus disease 2019 (COVID-19) as a pandemic disease globally on March 11, 2020, after it emerged in China. The emergence of COVID-19 has lasted over a year, and despite ...promising vaccine reports that have been produced, we still have a long way to go until such remedies are accessible to everyone. The immunomodulatory strategy has been kept at the top priority for the research agenda for COVID-19. Corticosteroids have been used to modulate the immune response in a wide range of diseases for the last 70 years. These drugs have been shown to avoid and reduce inflammation in tissues and the bloodstream through non-genomic and genomic effects. Now, the use of corticosteroids increased the chance of survival and relief by combating the viral strong inflammatory impacts and has moved to the forefront in the management of patients seeking supplemental oxygen. The goal of this review is to illuminate dexamethasone and methylprednisolone, i.e., in terms of their chemical and physical properties, role in COVID-19 patients suffering from pneumonia, the proposed mode of action in COVID-19, pharmacokinetics, pharmacodynamics, clinical outcomes in immunocompromised populations with COVID-19, interaction with other drugs, and contradiction to explore the trends and perspectives for future research. Literature was searched from scientific databases such as Science Direct, Wiley, Springer, PubMed, and books for the preparation of this review. The RECOVERY trial, a massive, multidisciplinary, randomized, and open-label trial, is mainly accountable for recommendations over the usage of corticosteroids in COVID-19 patients. The corticosteroids such as dexamethasone and methylprednisolone in the form of medication have anti-inflammatory, analgesic, and anti-allergic characteristics, including the ability to inhibit the immune system. These drugs are also recommended for treating symptoms of multiple ailments such as rheumatic and autoimmune diseases, leukemia, multiple myeloma, and Hodgkin's and non-Hodgkin's lymphoma along with other drugs. Toxicology studies proved them safe usually at low dosage
oral or other routes.
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