Biology subjects

Khan, Y.

Publications and source records attributed to Khan, Y..

12 recordsLinked to original sources

bioRxiv2026

Clonally Convergent Tph/Tfh-like CD4+ T Cells are Shared Across Recovery and Recurrence in Experimental Periodontitis

Periodontitis is a chronic inflammatory disease of the tooth-supporting structures (periodontium) that requires life-long maintenance to prevent progression. Using a sensitized model of recurrent periodontitis in mice (SeRPD), in which regulatory breakdown was induced by temporary Treg depletion concurrent with disease, we mapped the gingival T cell imprint across each disease phase. Transient regulatory breakdown left a durable mucosal imprint after clinical recovery, characterized by enrichment of local and regional CD4 T cells. Paired single-cell RNA and TCR sequencing of gingival immune cells identified a convergent clonotype expanded from recovery into recurrence that carried a Tfh/Tph-like transcriptional identity. An analogous CD4 T cell population was detected in human periodontitis lesions by single-cell transcriptomics. Together, these findings support a paradigm in which clinical recovery does not ensure a local T cell repertoire reset; instead, a reservoir of antigen-experienced, tissue-adapted CD4 T cells persist in the mucosa and participate in recurrence.

immunology↗

bioRxiv2026

Differential sensing with imprinted and non-imprinted organic electrochemical transistors reduces calibration drift in wearable sweat cortisol sensors

The output of a wearable cortisol sensor drifts over days for reasons unrelated to cortisol, so a calibration made on the first day soon stops being valid. In our differential organic electrochemical transistor, a PEDOT:PSS transistor coated with a molecularly imprinted polymer (MIP) for cortisol is paired with one coated with a non-imprinted polymer (NIP) of the same composition, and the NIP response is subtracted. Over four calibrations in artificial sweat across 14 days, the response of the MIP alone shifted by 15% to 22% of its range on day 1, whereas the differential output shifted by 1% to 10%, and the variation between days at 1 to 10nM fell by 65% to 70% on average for individual pairs. In sweat from one participant, read against the calibration from day 1, both outputs tracked the direction of visible changes in salivary cortisol, while the MIP alone diverged from the differential output, consistent with the laboratory drift.

bioengineering↗

bioRxiv2026

CD11c+ myeloid cells are the predominant CD4+CCR5+ immune population in the foreskin and are increased in men with HIV-associated penile anaerobes

Specific anaerobic species within the penile microbiome - Bacteria Associated with Seroconversion, Inflammation and Immune Cells (BASIC) - have been linked to increased HIV-1 susceptibility. These bacteria can directly disrupt epithelial integrity and are believed to increase local inflammation, resulting in an increased density of HIV-susceptible T cells in the inner foreskin. It is currently unknown whether other immune cells bearing the HIV entry receptors, CD4 and CCR5, are also elevated in individuals with a high abundance of BASIC species. Using inner foreskin tissues and penile swabs from males undergoing voluntary medical male circumcision, we performed a retrospective cross-sectional study to assess the relationship between BASIC species and the tissue density of such immune cells, including CD68+ macrophages, CD11c+ dendritic cells, and CD207+ Langerhans cells. The most abundant cells in the inner foreskin expressing the HIV co-receptors were CD11c+ dendritic cells (48.6% of CD4+/CCR5+ cells), followed by CD68+ macrophages (28.6%), CD3+ T cells (18.8%), and CD207+ Langerhans-like (8.8%) cells. The absolute abundance of BASIC species was associated with elevated tissue densities of both CD4+/CCR5+ T cells (as previously reported) and a heterogeneous population of CD3-/CD4+/CCR5+ cells of myeloid origin. In the dermis, BASIC species abundance was linked to elevated densities of cells expressing CD11c, CD68, and CD207, as well as those co-expressing CD11c and CD207; furthermore, CD11c+ and CD207+ cells were farther from the basement membrane in participants with a high abundance of BASIC species. Myeloid cells were not elevated in participants with a high abundance of control taxa. In an integrated analysis including previously published data from this same cohort, myeloid-cell densities clustered tightly together, positively correlated with BASIC species and pro-inflammatory cytokines, and had trends to negative correlations with control taxa (significant for CD207+ cell density). Overall, our findings suggest that BASIC species are associated with a broader foreskin immune phenotype marked by increased densities of HIV-susceptible myeloid and T cells, alongside epithelial disruption.

immunology↗

bioRxiv2026

Single-chip End-to-End Ingestible Electronics for Gut Neurotransmitter Sensing

Neurotransmitters in the gut play a vital role in human health and neuroscience, and their real-time monitoring is essential for understanding underlying physiological mechanisms. However, bioelectronic systems capable of measuring neurotransmitters in vivo at the anatomical site of interest remain underdeveloped and largely depend on bulky, off-the-shelf electronic components, thereby constraining the development of systems that are both practical and minimally invasive. Here, we report a miniature ingestible pill that is capable of real-time in vivo sensing of two key neurotransmitters: serotonin (5-HT) and dopamine (DA). The system incorporates a fully printed three-electrode-based electrochemical sensor for neurotransmitter sensing and a custom application-specific integrated circuit (ASIC) that integrates all major functional blocks on a single chip, enabling a platform for fully wireless monitoring of gut neurotransmitters. The pill, measuring 5.8 mm in diameter and 19 mm in length, supports multiple electrochemical sensing techniques, including amperometry and voltammetry, with only 42 A of average current consumption. We demonstrate the ingestible platform through in vivo studies in rat animal models, enabling real-time monitoring of gut neurotransmitters.

bioengineering↗

bioRxiv2026

Self-severing circuits facilitate passage of ingestible electronic sensor-guided therapeutics

Ingestible electronics enable the tracking and treatment of gastrointestinal and systemic diseases. However, bulky batteries and circuit boards require large capsules that can result in bowel obstruction, a medical emergency. Here, we engineered a 9 x 26 mm electronic pill capable of triggered severing into tiny pieces with sizes clinically proven to reduce obstruction risk. Our capsule enables multicomponent circuit boards to connect with separately encapsulated powering elements via conductive, interlocking connections. Heat induced softening of polyethylene glycol/polycaprolactone channels activates a spring to separate encapsulated components into inert 9 x 15 mm segments, facilitating intestinal passage. Separation triggers included closed-loop sensors and time-delay circuits. In vivo swine studies demonstrate the ability of our capsules to sense luminal oxygen changes via an optoelectronic sensor, locally trigger upadacitinib delivery, and facilitate safe excretion.

bioengineering↗

bioRxiv2024

Exploring Transcriptomic Changes in Antibiotic-Resistant Salmonella Heidelberg Modulated by Commensal Escherichia coli in Vitro

Nontyphoidal Salmonella (NTS) are major foodborne pathogens primarily transmitted to humans through contaminated poultry products. The increase in antibiotic-resistant NTS, including Salmonella Heidelberg, has recently become a public health issue. Current control measures are inadequate, emphasizing the need for novel approaches to mitigate NTS colonization in poultry and contamination of poultry products. We hypothesized that commensal Escherichia coli can reduce antibiotic-resistant NTS colonization in the chicken intestines by modulating the fitness, virulence, and antibiotic resistance (AMR) potential of Salmonella. To test this hypothesis, we co-cultured commensal E. coli 47-1826 and antibiotic-resistant S. Heidelberg 18-9079 strains isolated from poultry and analyzed their transcriptomes using RNA sequencing. Our analysis revealed 4,890 differentially expressed genes in S. Heidelberg 18-9079 when co-cultured with E. coli 47-1826. After filtering the expression data, we found 193 genes were significantly upregulated while 202 genes were downregulated. Notably, several genes involved in bacterial growth, pathogenicity and virulence, biofilm formation, metal-ion hemostasis, signal transduction and chemotaxis, stress response, transmembrane transport of xenobiotics, and cellular metabolism were down-regulated by as much as eighty-six folds in S. Heidelberg as compared to the control. Further, the study revealed the downregulation of genes associated with AMR and drug efflux in S. Heidelberg 18-9079 by up to twelvefold. These findings highlight that commensal E. coli 47-1826 may reduce the fitness, persistence, virulence, and antimicrobial resistance (AMR) dissemination of S. Heidelberg 18-9079, implying that E. coli strain 47-1826 could be utilized as a strategy to mitigate antibiotic-resistant S. Heidelberg in poultry, ultimately enhancing food safety. ImportanceNontyphoidal Salmonella, commonly transmitted to humans through contaminated poultry meat and eggs, is one of the most frequent causes of foodborne illness. Augmenting the situation, foodborne outbreaks of antibiotic-resistant NTS have become an additional food safety and public health concern. Evaluation of growth changes and transcriptomic profiling of antibiotic-resistant S. Heidelberg and commensal E. coli in a mixed culture of the two will provide insight into the ability of commensal E. coli to reduce S. Heidelberg colonization of chicken intestines and the genes involved in that change. Our study showed that commensal E. coli strain 47-1826 significantly reduced antibiotic-resistant S. Heidelberg 18-9079 counts and expression of Salmonella genes, which play a vital role in the growth and persistence of nontyphoidal Salmonella in poultry intestines. The study results suggest the potential use of commensal E. coli strain 47-1826 to control antibiotic-resistant S. Heidelberg colonization in poultry, leading to improved food safety through reduced NTS contamination of foods of poultry origin and reduced dissemination of antibiotic-resistant Salmonella and their resistant determinants to humans via the food chain.

microbiology↗

bioRxiv2024

Dysregulated Proteins in Plasma Distinguishing Syndromic from Non-syndromic Heritable Thoracic Aortic Disease

BACKGROUNDThoracic aortic aneurysms (TAA) are often found in younger individuals and approximately 20% may be associated with heritable thoracic aortic disease (HTAD). There are some data on genomic biomarkers reflecting inflammation and extracellular matrix remodeling in HTAD. However, data that accurately reflect the corresponding protein changes are scarce. Our aim was to quantify proteins by using targeted proteomics in HTAD patients versus healthy controls (HC). METHODSPatients with Loeys-Dietz syndrome (LDS, n = 8), Marfan syndrome (MFS, n = 11), and Aortic aneurysm, familial thoracic 6 syndrome (AAT6, n = 7) were recruited. For comparison, blood samples were drawn from 16 healthy controls (HC). Plasma samples were analyzed by targeted proteome analysis of 276 proteins using immunoaffinity proteomics. RESULTSSeven proteins were elevated when comparing HTAD to HC, displaying two patterns: i) Oncostatin M (OSM) and Pentraxin-3 (PTX3) were significantly higher in both LDS and MFS, with comparable levels in AAT6, reflecting a generalized increase in HTAD. ii) increased levels of TNF Receptor Superfamily Member 9 (TNFRSF9), Granulysin (GNLY), Glycoprotein 1b-alpha (GP1BA), Vasorin (VASN) and CD5 were restricted to the LDS subgroup and correlated positively with Th17 and platelet counts. CONCLUSIONSThe general increase in OSM and PTX3 in HTAD may reflect early but common mechanisms related to vascular inflammation while the distinct increase in TNFRSF9, GNLY, VASN, GP1BA and CD5 in LDS patients, may reflect involvement of Th17 inflammatory response mechanisms in the progression of TAA. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/624213v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@1234b26org.highwire.dtl.DTLVardef@1ad982org.highwire.dtl.DTLVardef@bdf438org.highwire.dtl.DTLVardef@ec9c67_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

SMIM36, a novel and conserved microprotein, is involved in retinal lamination in zebrafish.

Microproteins are small proteins comprising 2 to 200 amino acids, arising from small Open Reading Frames (smORFs). They are found in different parts of the cell and regulate basic molecular processes like DNA replication, repair, transcription and recombination. SMIM or SMall Integral Membrane proteins are novel, largely uncharacterized, members to the class of microproteins defined by the presence of a transmembrane domain. The retinal transcriptome of zebrafish, reported previously by our group, revealed several novel mRNA transcripts that show oscillating expression in a diurnal manner. Here, we show that one of these transcripts encodes the zebrafish homolog of the human SMIM36 protein, which has not been functionally characterised. This highly conserved microprotein is expressed in the human and zebrafish retina, and efficiently translated in cell lines. Using single-cell RNA-seq datasets, we found that it is expressed in the bipolar cells, rods and Muller glia in the human retina. The knockdown of SMIM36 using splice-block morpholino caused microphthalmia and defects in the retinal layers in zebrafish. Therefore, we show the role of a microprotein in the neural retina thus paving the way for future studies on the role of SMIM proteins in retinal disorders.

developmental biology↗

bioRxiv2021

A flexible electronic strain sensor for the real-time monitoring of tumor progression

Healthcare professionals and scientists utilize tumor shrinkage as a key metric to establish the efficacy of cancer treatments. However, current measurement tools such as CT scanners and calipers only provide brief snapshots of the dynamic geometric changes occurring in vivo, and they are unable to characterize the continuous micrometer-scale volumetric transformations transpiring at minute timescales. Here we present a stretchable electronic strain sensor, with a 10-micron scale resolution, capable of continuously monitoring tumor volume progression in real-time. In mouse models with subcutaneously implanted lung cancer or B-cell lymphoma tumors our sensors discerned a significant change in the tumor volumes of treated mice within 5 hours after small molecule therapy or immunotherapy initiation. Histology, caliper measurements, and luminescence imaging over a one-week treatment period validated the data from the continuous sensor. We anticipate that real-time tumor progression datasets could help expedite and automate the process of screening cancer therapies in vivo.

bioengineering↗

bioRxiv2021

Design considerations of a wearable electronic-skin for mental health and wellness: balancing biosignals and human factors

Chronic stress has been associated with a variety of pathophysiological risks including developing mental illness. Conversely, appropriate stress management, can be used to foster mental wellness proactively. Yet, there is no existing method that accurately and objectively monitors stress. With recent advances in electronic-skin (e-skin) and wearable technologies, it is possible to design devices that continuously measure physiological parameters linked to chronic stress and other mental health and wellness conditions. However, the design approach should be different from conventional wearables due to considerations like signal-to-noise ratio and the risk of stigmatization. Here, we present a multi-part study that combines user-centered design with engineering-centered data collection to inform future design efforts. To assess human factors, we conducted an n=24 participant design probe study that examined perceptions of an e-skin for mental health and wellness as well as preferred wear locations. We complement this with an n=10 and n=16 participant data collection study to measure physiological signals at several potential wear locations. By balancing human factors and biosignals, we conclude that the upper arm and forearm are optimal wear locations.

bioengineering↗

bioRxiv2020

Insect wing extract: A novel source for green synthesis of nanoparticles of antioxidant and antimicrobial potential

Silver nanoparticles (AgNPs) are among the most widely synthesized and used nanoparticles (NPs). AgNPs have been traditionally synthesized from plant extracts, cobwebs, microorganisms, etc. However, their synthesis from wing extracts of common insect; Mang mao which is abundantly available in most of the Asian countries has not been explored yet. We report the synthesis of AgNPs from M. mao wings extract and its antioxidant and antimicrobial activity. The synthesized AgNPs were spherical, 40-60 nm in size and revealed strong absorption plasmon band around at 430 nm. Highly crystalline nature of these particles as determined by Energy-dispersive X-ray analysis and X-ray diffraction further confirmed the presence of AgNPs. Hydrodynamic size and zeta potential of AgNPs were observed to be 43.9 nm and -7.12 mV, respectively. Fourier-transform infrared spectroscopy analysis revealed the presence of characteristic amide proteins and aromatic functional groups. Thin-layer chromatography (TLC) and Gas chromatography-mass spectroscopy (GC-MS) analysis revealed the presence of fatty acids in the wings extract that may be responsible for biosynthesis and stabilization of AgNPs. Further, SDS-PAGE of the insect wing extract protein showed the molecular weight of 49 kDa. M. mao silver nanoparticles (MMAgNPs) exhibit strong antioxidant, broad-range antibacterial and antifungal activities, which signifies their biomedical and agricultural potential.

microbiology↗

bioRxiv2020

Metastatic Site Prediction in Breast Cancer usingOmics Knowledge Graph and Pattern Mining withKirchhoff's Law Traversal

Predicting the anatomical site of metastasis from a primary tumour remains an unsolved problem in breast cancer (BRCA) and metastatic disease more broadly. The difficulty is structural: metastatic biology is multi-site (bone, lung, liver, brain), multi-omics (genomics, proteomics, methylomics, drug response), and multi-modal (CNV, gene expression, DNA methylation, pathways, clinical associations). Existing classifiers either collapse this heterogeneity into a single feature vector or rely on a single omics layer, both of which discard the mechanistic structure that drives metastatic tropism. We introduce Kirchhoff Knowledge Graphs (K-KG), a framework that imports the conservation laws of electrical-circuit theory into knowledge graph reasoning. Our contributions are: (1) a layered RDF Cancer Decision Network integrating 36 polyomics datasets across mutations, pathways, drugs, diseases, and reactions; (2) two novel conservation laws--the Knowledge-Graph Voltage Law (KGVL) and Knowledge-Graph Current Law (KGCL)--that govern information flow during traversal and yield a principled measure of graph completeness; (3) topological motif mining on the conserved graph, replacing expression-based feature selection by identifying triangular sub-structures whose rewiring marks metastatic transition; (4) a Graph Convolutional Neural Network whose hidden layers are the omics layers themselves, predicting site-specific metastasis as a continuous percentage rather than a binary label. On TCGA-BRCA training plus one validation and four independent test cohorts from GEO, K-KG achieves 83.8% AUC for relapse prediction and up to 0.87 AUC / 0.91 F1 for Brain-site-specific prediction, outperforming Random Forest, Neural Network, and SVM baselines by 8-20 AUC points. To our knowledge this is the first application of Kirchhoffs laws (1845, 1847) to graph-based machine learning, and the first metastasis predictor that returns a per-site contribution profile rather than a single label.

bioinformatics↗