Design of cobalt-doped graphene quantum dot-decorated vanadium pentoxide nanosheet-based Off-On fluorescent sensor system for tiopronin sensing.

Despite the high medicinal value of tiopronin, there are substantial adverse effects such as yellow skin, yellow eyes, muscle aches, etc. Therefore, there is a huge necessity to identify tiopronin using advanced sensors in provided samples. Recently, the preference for graphene quantum dots (GQDs) and inorganic nanomaterial-based fluorescent sensors for the detection of pharmaceuticals has been extensively documented due to their plentiful advantages. Therefore, in this work, the cobalt-doped GQDs decorated vanadium pentoxide nanosheet-based fluorescence switch 'Off-On' sensor (Co-GQDs@V2O5-NS) was designed for highly sensitive and selective detection of tiopronin. Briefly, the green synthesis of highly fluorescent Co-GQDs was carried out using a hydrothermal method. Meanwhile, the synthesis of V2O5-NS was synthesized using the liquid exfoliation method. The synthesis of Co-GQDs@V2O5-NS was accomplished wherein Co-GQDs adsorbed on the surface of V2O5-NS that offered the quenching of fluorescence of Co-GQDs. Afterward, the addition of tiopronin into the quenched probe disclosed the proportional recovery of fluorescence of Co-GQDs. Here, the addition of tiopronin provides the decomposition of V2O5-NS and conversion into the V4+ that aids in releasing the quenched fluorescence of Co-GQDs. The limit of detection and linearity range for tiopronin was found to be 1.43 ng/mL and 10-700 ng/mL, respectively. Moreover, it demonstrated high selectivity, good stability at experimental conditions, and practicality in analyzing tiopronin in spiked sample analysis. Hence, the designed Co-GQDs@V2O5-NS nanosized sensor enables high sensitivity, selectivity, simplicity, label-free, and eco-friendly tiopronin recognition. In the future, the utility of Co-GQDs@V2O5-NS can open a new door for sensing tiopronin in provided samples.

Concept mapping a potential pedagogical strategy to foster meaningful learning in physiology students.

BACKGROUND: Understanding of human physiology is critical for clinical practice and disease management. Escalating the teaching-learning method to improve conceptual knowledge may help the students to apply their knowledge in clinical scenarios. The present study was conducted to teach the use of concept mapping as a learning strategy to foster meaningful learning in physiology, compare its impact as a learning tool with traditional methods on meaningful learning, assess the cognitive gain, and find student's perception regarding concept mapping. MATERIALS AND METHODS: The interventional study was conducted on first-year MBBS students. Depending upon marks obtained in previous internal assessments, the students were classified into "rapid learners" (RL) and "potential learners" (PL). By simple random sampling technique, both groups were divided into interventional (concept mapping) and control groups (question-answer discussion). After a pretest, all students had a lecture on glomerular filtration. The assignment was given to the interventional group to prepare a concept map on glomerular filtration, and question-answer were discussed for control groups. A surprise posttest was conducted after 2-3 days. RESULT: In our study, all four groups showed significant differences in the pretest and posttest scores using a paired t-test (P < 0.05). The mean score of gain in learning, raw gain (G0), absolute learning gain, relative learning gain, and average normalized gain compared between the interventional group and controls group showed statistically significant performance improvement in both RL and PL groups. CONCLUSION: The concept mapping strategy was more efficacious than the question-answer discussion. Concept mapping is an impactful learning tool to improve cognitive gain and potential pedagogical strategy to foster meaningful learning in physiology students.

A pairwise cytokine code explains the organism-wide response to sepsis.

Sepsis is a systemic response to infection with life-threatening consequences. Our understanding of the molecular and cellular impact of sepsis across organs remains rudimentary. Here, we characterize the pathogenesis of sepsis by measuring dynamic changes in gene expression across organs. To pinpoint molecules controlling organ states in sepsis, we compare the effects of sepsis on organ gene expression to those of 6 singles and 15 pairs of recombinant cytokines. Strikingly, we find that the pairwise effects of tumor necrosis factor plus interleukin (IL)-18, interferon-gamma or IL-1ß suffice to mirror the impact of sepsis across tissues. Mechanistically, we map the cellular effects of sepsis and cytokines by computing changes in the abundance of 195 cell types across 9 organs, which we validate by whole-mouse spatial profiling. Our work decodes the cytokine cacophony in sepsis into a pairwise cytokine message capturing the gene, cell and tissue responses of the host to the disease.

Design of lactoferrin functionalized carboxymethyl dextran coated egg albumin nanoconjugate for targeted delivery of capsaicin: Spectroscopic and cytotoxicity studies.

The increased mortality rates associated with colorectal cancer highlight the pressing need for improving treatment approaches. While capsaicin (CAP) has shown promising anticancer activity, its efficacy is hampered due to low solubility, rapid metabolism, suboptimal bioavailability, and a short half-life. Therefore, this study aimed to prepare a lactoferrin-functionalized carboxymethyl dextran-coated egg albumin nanoconjugate (LF-CMD@CAP-EGA-NCs) for the targeted CAP delivery to enhance its potential for colorectal cancer therapy. Briefly, LF-CMD was synthesized through an esterification reaction involving LF as a receptor and CMD as a shell. Concurrently, CAP was incorporated into an EGA carrier using gelation and hydrophobic interactions. The subsequent production of LF-CMD@CAP-EGA-NCs was achieved through the Maillard reaction. Spectral characterizations confirmed the successful synthesis of smooth and spherical-shaped LF-CMD@CAP-EGA-NCs using LF-CMD and EGA-CAP nanoparticles, with high entrapment efficiency and satisfactory drug content. Furthermore, LF-CMD@CAP-EGA-NCs demonstrated a sustained release of CAP (76.52 ± 1.01 % in 24 h, R2 = 0.9966) in pH 5.8 buffer with anomalous transport (n = 0.68) owing to the shell of the CMD and EGA matrix. The nanoconjugate exhibited enhanced cytotoxicity in HCT116 and LoVo cell lines, which is attributed to the overexpression of LF receptors in colorectal HCT116 cells. Additionally, LF-CMD@CAP-EGA-NCs demonstrated excellent biocompatibility, as observed in the FHC-CRL-1831 cell line. In conclusion, LF-CMD@CAP-EGA-NCs can be considered as a promising approach for targeted delivery of CAP and other anticancer agents in colorectal cancer treatment.

Zinc metal-organic frameworks- graphene quantum dots nanocomposite mediated highly sensitive and selective fluorescence "On-Off-On" probe for sensing of quercetin.

Presently, there is a necessity to design novel methods because of quercetin's significant biological relevance. Therefore, we developed the rose petal-derived graphene quantum dots embedded zinc metal organic frameworks (RP-GQDs@Zn-MOFs) based fluorescence "On-Off-On" nanoprobe for quercetin sensing. Initially, RP-GQDs were synthesized using rose petal waste and then subjected to embedding into Zn-MOFs. Herein, the addition of copper ions (Cu2+) results in fluorescence "Switch Off" whereas quercetin inclusion resulted in the formation of the quercetin-Cu2+ complex. It regains the RP-GQDs@Zn-MOFs quenched fluorescence termed as "Switch On" because of the static quenching mechanism. It demonstrated a wide concentration range and low detection limit of 100 ng/mL to 1400 ng/mL (R2=0.99) and 37.84 ng/mL, respectively. The selectivity study shows the high specificity for quercetin in presence of interfering compounds because of Cu2+ coordination between the carbonyl oxygen atom and the 3-OH group of quercetin. Moreover, the designed probe shows good stability, repeatability, and real-time analysis possibility.

3D QSAR study on substituted 1, 2, 4 triazole derivatives as anticancer agents by kNN MFA approach.

Background and objectives: Researchers have recently focused on the biological and synthetic effects of 1, 2, and 4-triazole fused heterocyclic molecules because they have tremendous medicinal value. The objective of the present study was to carry out the 3D QSAR evaluation on the substituted 1,2, and 4 triazole derivatives for anticancer potential using k-Nearest Neighbor-Molecular Field Analysis (kNN-MFA) method. Methods: Using the molecular design suite, a three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was undertaken on a series of 4-amino-5-(pyridin3yl)-4H-1, 2, and 4-triazole-3-thiol anticancer drugs (Vlife MDS). This study used a genetic algorithm and a manual selection approach on 20 substituted 1, 2, and 4-triazole derivatives. Based on the genetic algorithm (GA), the 3D-QSAR model was generated. Statistical significance and predictive capacity were evaluated using internal and external validation. Results: The most significant model has a correlation coefficient of 0.9334 (squared correlation coefficient r2 = 0.8713), showing that biological activity and descriptors have a strong relationship. The model exhibited internal predictivity of 74.45 percent (q2 = 0.2129), external predictivity of 81.09 percent (pred r2 = 0.8417), and the smallest error term for the predictive correlation coefficient (pred r2se = 0.1255). The model revealed steric (S 1047--0.0780--0.0451S 927) and electrostatic (E 1002) data points that contribute remarkably to anticancer activity. A molecular field study demonstrates a link between the structural features of substituted triazole derivatives and their activities. Conclusion: The good-to-moderate anticancer potential of compounds confirms the significant pharmacological role of 1,2,4-triazole derivatives. These results could lead to the identification of potential chemical compounds with optimal anticancer activity and minimal side effects.

Retraction Note: Luffa cylindrica: a promising herbal treatment in progesterone induced obesity in mice.

[This retracts the article DOI: 10.1007/s40200-021-00749-8.].

Wear behaviour of lithography ceramic manufactured dental zirconia.

OBJECTIVE: The study aims to evaluate the wear surface using 3D surface roughness and other material characterization of zirconia fabricated using photopolymerization based Lithography-based Ceramic Manufacturing (LCM). METHOD: LCM technology was used to fabricate zirconia specimens of size 10 × 10 × 2mm3. Scanning Electron Microscope, 3D-profilometer, X-ray Diffraction, and hardness test characterized the samples before and after wear and Coefficient of friction (COF) was monitored. RESULT: The COF was around 0.7 and did not differ much between the horizontally and vertically printed specimens. However, the surface roughness after wear for horizontally printed specimen was 0.567 ± 0.139 µm, while that for vertically printed specimen was 0.379 ± 0.080 µm. The reduced valley depth and the dale void volume were low for the vertically printed zirconia specimen, indicating lesser voids and low fluid retention. In addition, it was observed that the hardness value of the vertically printed sample was better. The scanning electron microscopic images and 3D surface profiles of the zirconia specimens depicted the surface topography and revealed the wear track. CONCLUSION: The study shows that zirconia fabricated using LCM technology possesses surface roughness of about 0.5 µm with no machining scars that are usually associated with CAD/CAM dentistry and also indicating agreement with clinically acceptable values for minimal surface roughness of dental restorations. Dental restorations using LCM fabricated zirconia redues the requirement of post-processing work flow that is part of CAD/CAM dentistry.

Organism-Wide Analysis of Sepsis Reveals Mechanisms of Systemic Inflammation.

Sepsis is a systemic response to infection with life-threatening consequences. Our understanding of the impact of sepsis across organs of the body is rudimentary. Here, using mouse models of sepsis, we generate a dynamic, organism-wide map of the pathogenesis of the disease, revealing the spatiotemporal patterns of the effects of sepsis across tissues. These data revealed two interorgan mechanisms key in sepsis. First, we discover a simplifying principle in the systemic behavior of the cytokine network during sepsis, whereby a hierarchical cytokine circuit arising from the pairwise effects of TNF plus IL-18, IFN-γ, or IL-1ß explains half of all the cellular effects of sepsis on 195 cell types across 9 organs. Second, we find that the secreted phospholipase PLA2G5 mediates hemolysis in blood, contributing to organ failure during sepsis. These results provide fundamental insights to help build a unifying mechanistic framework for the pathophysiological effects of sepsis on the body.

Secondary Progressive Multiple Sclerosis: A Review of Clinical Characteristics, Definition, Prognostic Tools, and Disease-Modifying Therapies.

Many challenges exist in the precise diagnosis and clinical management of secondary progressive multiple sclerosis (SPMS) because of the lack of definitive clinical, imaging, immunologic, or pathologic criteria that demarcate the transition from relapsing-remitting MS to SPMS. This review provides an overview of the diagnostic criteria/definition and the heterogeneity associated with different SPMS patient populations; it also emphasizes the importance of available prospective/retrospective tools to identify patients with SPMS earlier in the disease course so that approved disease-modifying therapies and nonpharmacological strategies will translate into better outcomes. Delivery of such interventions necessitates an evolving patient-clinician dialog within the context of a multidisciplinary team.

Assessment of Urinary Biomarkers for Infectious Diseases Using Lateral Flow Assays: A Comprehensive Overview.

Screening of biomarkers is a powerful approach for providing a holistic view of the disease spectrum and facilitating the diagnosis and prognosis of the state of infectious diseases. Unaffected by the homeostasis mechanism in the human body, urine accommodates systemic changes and reflects the pathophysiological condition of an individual. Easy availability in large volumes and non-invasive sample collection have rendered urine an ideal source of biomarkers for various diseases. Infectious diseases may be communicable, and therefore early diagnosis and treatment are of immense importance. Current diagnostic approaches preclude the timely identification of clinical conditions and also lack portability. Point-of-care (POC) testing solutions have gained attention as alternative diagnostic measures due to their ability to provide rapid and on-site results. Lateral flow assays (LFAs) are the mainstay in POC device development and have attracted interest owing to their potential to provide instantaneous results in resource-limited settings. The discovery and optimization of a definitive biomarker can render POC testing an excellent platform, thus impacting unwarranted antibiotic administration and preventing the spread of infectious diseases. This Review summarizes the importance of urine as an emerging biological fluid in infectious disease research and diagnosis in clinical settings. We review the academic research related to LFAs. Further, we also describe commercial POC devices based on the identification of urinary biomarkers as diagnostic targets for infectious diseases. We also discuss the future use of LFAs in developing more effective POC tests for urinary biomarkers of various infections.

3-D Surface Morphological Characterization of CAD/CAM Milled Dental Zirconia: An In Vitro Study of the Effect of Post-Fabrication Processes.

Objective: To investigate the effect on zirconia surface of the post-fabrication surface treatments on the morphological characteristics and mechanical properties of CAD/CAM milled dental zirconia specimens as well as to identify the critical parameters in the measurement of oral retention under in vitro circumstances. Method: The zirconia specimens (N = 20, n = 4) were subjected to CAD/CAM milling and divided into five groups. The specifications were: Group G1­sintered; Group G2­sintered followed by a polishing process; Group G3­sintered followed by polishing and sandblasting with alumina particles Al2O3 (110 µm); Group G4­sintered followed by sandblasting; Group G5­sintered followed by sandblasting with polishing as the end process. All the groups were subjected to Fretting wear tests, 3-D surface roughness measurements, and Vickers's Micro hardness tests. Investigation of the phase transformation using XRD, and surface feature examination using SEM were also carried out. Additionally, one-way ANOVA, Tukey, and Pearson correlations were statistically analysed. Results: The fabrication processes had a significant effect on the performance of zirconia specimens in all the groups (p > 0.05). Specimens that underwent polishing as the last process exhibited lower surface roughness. The monoclinic phase of zirconia was observed in all the specimens before and after wear except for those in the G2 and G5 groups, where polishing was the end process. In G5, the post-wear surface properties revealed lower surface roughness and hardness. Further, the SEM and 3-D topography show grooves as seen by the dale void volume (Vvv) values; shallow valley depth (Svk); micro craters; and wear track. Conclusion: Specimens in G5 that were subjected to multistep post-fabrication process, namely sandblasting followed by polishing, yielded better results when compared to those in the other groups (G1, G2, G3, and G4). G5 with an interlayer of alumina is recommended for clinical applications due to its enhanced surface properties, mechanical properties, and low wear.

Design of "Turn-Off" Fluorescent Nanoprobe for Highly Sensitive Detection of Uric Acid using Green Synthesized Nitrogen-Doped Graphene Quantum Dots.

Green synthesized graphene quantum dots (GQD) have been doped with nitrogen in an attempt to boost their optical characteristics and application sectors. In the present investigation, the blue luminescent nitrogen-doped GQDs (N-GQDs) were synthesized by single-step hydrothermal synthesis using tamarind shell powder as a precursor. The particle size and zeta potential of N-GQDs were found to be 11.40 nm and be -35.53 mV, respectively. A quantum yield as high as 23.78 % was accomplished at an excitation wavelength of 330 nm at neutral pH. It gets quenched sensitively in the existence of uric acid (UA) combining static quenching, electron transfer, and an inner filter effect mechanism. A linear range was obtained for UA from 10 µM to 100 µM, with a limit of detection (LOD) of 401.72 ± 0.04 pM. Additionally, the N-GQDs were selective toward UA in presence of metal ions and biomolecules that indicated its impending use to monitor UA in clinical samples. In conclusion, this work demonstrates that the N-GQDs as a sensing probe for UA recognition with notable advantages including socioeconomic, simple, and less time-consuming methods as compared to other methods. In the future, it can be potentially explored as a biosensor for UA detection in clinical samples.

Qualitative differences in disease-associated MEK mutants reveal molecular signatures and aberrant signaling-crosstalk in cancer.

Point-mutations of MEK1, a central component of ERK signaling, are present in cancer and RASopathies, but their precise biological effects remain obscure. Here, we report a mutant MEK1 structure that uncovers the mechanisms underlying abnormal activities of cancer- and RASopathy-associated MEK1 mutants. These two classes of MEK1 mutations differentially impact on spatiotemporal dynamics of ERK signaling, cellular transcriptional programs, gene expression profiles, and consequent biological outcomes. By making use of such distinct characteristics of the MEK1 mutants, we identified cancer- and RASopathy-signature genes that may serve as diagnostic markers or therapeutic targets for these diseases. In particular, two AKT-inhibitor molecules, PHLDA1 and 2, are simultaneously upregulated by oncogenic ERK signaling, and mediate cancer-specific ERK-AKT crosstalk. The combined expression of PHLDA1/2 is critical to confer resistance to ERK pathway-targeted therapeutics on cancer cells. Finally, we propose a therapeutic strategy to overcome this drug resistance. Our data provide vital insights into the etiology, diagnosis, and therapeutic strategy of cancers and RASopathies.

Ficus benghalensis promotes the glucose uptake- Evidence with in silico and in vitro.

Background: Ficus benghalensis L. is traditionally used to manage diabetes; also used in various herbal formulations, and is indicated as an insulin sensitizer. Hence, present work attempted in identifying the probable lead hits to promote glucose uptake via computational approach followed by experimental evaluation of hydroalcoholic extract of Ficus benghalensis L. bark in yeast cells. Methods: The in vitro assay for glucose uptake was performed in the baker yeast whereas in-silico study involved retrieving the phytoconstituents from open sources, and predicting for probable targets of diabetes followed by drug-likeness score, probable side effects, and ADMET profile. Homology modeling was performed to construct the target protein glucose transporter-2. In addition, the binding affinity of each ligand with glucose transporter was predicted using AutoDock 4.2. Results: A total of 17 phytoconstituents from F. benghalensis were identified to possess the anti-diabetic effects. Among them, 4-methoxybenzoic acid scored the highest drug-likeness score and lupeol acetate had the maximum binding affinity of -8.02 kcal/mol with 9 pi-interactions via Tyr324, Phe323, Ile319, Ile200, Ile28, Phe24, and Ala451. Similarly, the extract showed the highest glucose uptake efficacy in yeast cells at 500 µg/mL. Conclusion: Herein the present study reflected the probable activity of the phytoconstituents from F. benghalensis in promoting the glucose uptake via the in silico and in vitro approaches.

GLUT-2 mediated glucose uptake analysis of Duranta repens: In-silico and In-vitro approach.

Background: Type-2 diabetes mellitus is a common metabolic disorder characterized by insulin resistance, a relative impairment in insulin secretion, and a certain degree of genetic predisposition. The rapid rise in the prevalence of diabetes mellitus around the world has assisted in the development of new pharmacologically active compounds. The current study was aimed to investigate and validate the anti-diabetic activity of wild-grown plant Duranta repens L. Material and methods: In-silico molecular docking via AutoDock tools 4.2 and in-vitro glucose uptake assay using yeast cells was performed to investigate the anti-diabetic property of plant Duranta repens. Further, mRNA-based gene ontology enrichment analysis was performed to predict the imitated ontology by the bio-actives from Duranta repens. Results: The in-silico study results reveal that among the 9 active phytoconstituents docked against GLUT-2 protein, α-onocerin possessed the highest binding affinity of -10.23 kcal/mol with no predicted adverse effects and also complies with Lipinski's rule of five. Also, in-vitro studies reflected in a 5 mM glucose solution, hydro-alcoholic extract of Duranta repens at different concentrations enhanced glucose uptake in yeast cells. Conclusion: Duranta repens extract enhanced the glucose uptake in yeast cells which may be due to the presence of α-onocerin; possessed the better interaction. Also, no adverse effects were predicted for α-onocerin. Thus, it can be speculated  that Duranta repens may possess anti-diabetic activity which may be due to α-onocerin and other related bioactives; needs to be further confirmed vi a  experimental studies.

Blood Neurofilament Light in Progressive Multiple Sclerosis: Post Hoc Analysis of 2 Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: To investigate the potential of plasma neurofilament light (pNfL) as a biomarker of disease progression and treatment response in progressive multiple sclerosis (PMS) with and without acute disease activity. METHODS: A post hoc blinded analysis of pNfL levels in 2 placebo-controlled, phase 3 studies in secondary progressive multiple sclerosis (SPMS; EXPAND) and primary progressive multiple sclerosis (PPMS; INFORMS) using siponimod and fingolimod, respectively, as active compounds was performed. pNfL levels were quantified using a single molecule array (Homebrew Simoa) immunoassay from stored ethylenediaminetetraacetic acid (EDTA) plasma samples of all patients who consented for exploratory biomarker analysis in either study; pNfL levels were divided into high (≥30 pg/mL) and low (<30 pg/mL) at baseline. We investigated the association of pNfL levels with disability progression, cognitive decline, and brain atrophy and their sensitivity to indicate treatment response through clinical measures. RESULTS: We analyzed pNfL in 4,185 samples from 1,452 patients with SPMS and 1,172 samples from 378 patients with PPMS. Baseline pNfL levels were higher in SPMS (geomean 32.1 pg/mL) than in PPMS (22.0 pg/mL; p < 0.0001). In both studies, higher baseline pNfL levels were associated with older age, higher Expanded Disability Status Scale score, more Gd+ lesions, and higher T2 lesion load (all p < 0.05). Independent of treatment, high vs low baseline pNfL levels were associated with significantly higher risks of confirmed 3-month (SPMS [32%], hazard ratio [95% CI] 1.32 [1.09-1.61]; PPMS [49%], 1.49 [1.05-2.12]) and 6-month disability progression (SPMS [26%], 1.26 [1.01-1.57]; PPMS [48%], 1.48 [1.01-2.17]), earlier wheelchair dependence (SPMS [50%], 1.50 [0.96-2.34]; PPMS [197%], 2.97 [1.44-6.10]), cognitive decline (SPMS [41%], 1.41 [1.09-1.84]), and higher rates of brain atrophy (mean change at month 24: SPMS, -0.92; PPMS, -1.39). Baseline pNfL levels were associated with future disability progression and the degree of brain atrophy regardless of presence or absence of acute disease activity (gadolinium-enhancing lesions or recent occurrence of relapses before baseline). pNfL levels were lower in patients treated with siponimod or fingolimod vs placebo-treated patients and higher in those having experienced disability progression. DISCUSSION: pNfL was associated with future clinical and radiologic disability progression features at the group level. pNfL was reduced by treatment and may be a meaningful outcome measure in PMS studies. TRIAL REGISTRATION INFORMATION: EXPAND (ClinicalTrials.gov identifier: NCT01665144) and INFORMS (ClinicalTrials.gov identifier: NCT00731692).

AI-driven streamlined modeling: experiences and lessons learned from multiple domains.

Model-driven technologies (MD*), considered beneficial through abstraction and automation, have not enjoyed widespread adoption in the industry. In keeping with the recent trends, using AI techniques might help the benefits of MD* outweigh their costs. Although the modeling community has started using AI techniques, it is, in our opinion, quite limited and requires a change in perspective. We provide such a perspective through five industrial case studies where we use AI techniques in different modeling activities. We discuss our experiences and lessons learned, in some cases evolving purely modeling solutions with AI techniques, and in others considering the AI aids from the beginning. We believe that these case studies can help the researchers and practitioners make sense of various artifacts and data available to them and use applicable AI techniques to enhance suitable modeling activities.

Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology.

Immune cell dysregulation and lymphopenia characterize COVID-19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study, we evaluated the association of circulating IL-6, soluble mucosal addressin cell adhesion molecule (sMAdCAM), and IL-15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19. A cohort of SARS-CoV-2 infected individuals (n = 130) at various stages of disease progression together with healthy controls (n = 16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 levels. sMAdCAM, IL-15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells, were observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL-6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, plasma IL-15 levels negatively correlated with T, B, and NK count suggesting a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL-15 and IL-6, but not sMAdCAM, were associated with a longer duration of hospitalization.