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The development of paper-based devices has drawn a significant amount of attention, ranging from the creation of paper electronics to microfluidic devices. The flow of fluids through the paper substrate can be controlled by establishing a variety of barriers, which can be accomplished by either cutting or producing layers that are hydrophobic. Through the utilisation of this feature, a number of investigations, including mixing, modifying, and analytical studies, have been carried out on the paper substrate. However, because of the difficulties associated with its wettability, it is seldom investigated for the purpose of conducting evaporation studies of droplets. Traditionally, evaporation studies are carried out on a solid substrate like glass or silicon. Here we report a paper chip employing an impedance method to determine the characteristics of the droplet. It is also possible to determine the identity of the droplet by utilising the dielectric property of the liquid on a paper chip. A comparison is made between the traditional method of evaporation and the usage of the paper chip for the purpose of studying the evaporation of various liquids, ranging from ionic chemicals to volatile compounds. A subsequent step involves the utilisation of an electrical equivalent circuit in order to acquire the complex system attribute of the evaporation of the cellulose fibres. Finally, this reveals that paper chips have a significant amount of promise for use in scientific applications regarding evaporation analysis.

The sensing behavior of a MoS2-functionalized paper sensor towards dopamine was explored through a combinatorial approach of theoretical analysis, subsequent experimental validation, and machine-learning-driven predictive modeling of the measured electrochemical outputs. The suitability of the chosen 2D material for efficient detection of dopamine was confirmed using density functional theory. The physisorption behavior along with electrostatic interaction due to the incorporation of dopamine on MoS2was unraveled under the purview of theoretically estimated noncovalent interaction and charge density difference plot. The theoretical Löwdin population analysis elucidates the alteration in oxidation potential of dopamine, as observed in electrochemical experiments. The electrochemical responses of the developed sensor with the spiked serum samples showed an average accuracy of more than 96% with a limit of detection of 10 nM. Furthermore, implementation of a machine-intelligent interactive web app interface improved the resolution of the sensing platform significantly with an enhanced accuracy of nearly 99%.

Cervical atresia is a rare congenital Müllerian duct anomaly that manifests as the absence or deformed nonfunctional presence of the cervix. Herein, a multi-layered biodegradable stent is fabricated using a homogeneous blend of silk fibroin with polycaprolactone using hexafluoroisopropanol as a common solution. Briefly, a concentric cylinder of 3D honeycomb layer is sandwiched within electrospun sheets for fixing at the cervico-uterine junction to pave the way of cervical reconstruction. An average length of 40 mm with 3 mm diameter is fabricated for the hybrid stent design. SEM evidences an evenly distributed pore architecture of the electrospun layer, and mechanical characterization of stent reveals a tensile strength of 1.7 ± 0.2 MPa, with a Young’s modulus of 5.9 ± 0.1 MPa. Physico-chemical characterization confirms the presence of silk fibroin and poly caprolactone within the engineered stent. Following 14 days of pepsin enzymatic degradation, 18% degradation and a contact angle measurement of 97° are observed. In vitro cytocompatibility studies are performed using site-specific primary human cervical squamous, columnar epithelial cells, and human endometrial stromal cells. The study demonstrates non-cytotoxic cells’ viability (no significant toxicity), improved cell anchoring, adherence among the stent layers, and proliferation in the 3D microenvironment. Furthermore, in vivo subcutaneous studies in the rodent model indicate that the implanted stent undergoes constructive remodeling, neo-tissue creation, neo-vasculature formation, and re-epithelialization while maintaining patency for 2 months.

Regeneration of full-thickness wounds without scar formation is a multifaceted process, which depends on in situ dynamic interactions between the tissue-engineered skin substitutes and a newly formed reparative tissue. However, the majority of the tissue-engineered skin substitutes used so far in full-thickness wound healing cannot mimic the natural extracellular matrix (ECM) complexity and thus are incapable of providing a suitable niche for endogenous tissue repair. Herein, we demonstrated a simple approach to fabricate porous hybrid ECM sponges (HEMS) using a placental ECM and silk fibroin for full-thickness wound healing. HEMS with retained cytokines/growth factors provided a noncytotoxic environment in vitro for human foreskin fibroblasts (HFFs), human epidermal keratinocytes (HEKs), and human amniotic membrane-derived stem cells to adhere, infiltrate, and proliferate. Interestingly, HEMS-conditioned media accelerated the migration of HFFs and HEKs owing to the presence of cytokines/growth factors. Also, the ex vivo chick chorioallantoic membrane assay of HEMS demonstrated its excellent vascularization potential by inducing and supporting blood vessels. Additionally, HEMS when subcutaneously implanted demonstrated no severe immune response to the host. Furthermore, HEMS implanted in full-thickness wounds in a rat model showed augmented healing progression with well-organized epidermal–dermal junctions via pronounced angiogenesis, accelerated migration of HFFs/HEKs, enhanced granulation tissue formation, and early re-epithelialization. Taken together, these findings show that porous HEMS ornamented with cytokines/growth factors having superior physicomechanical properties may be an appropriate skin substitute for full-thickness cutaneous wounds.

The burden of cardio-vascular and other age-related non-communicable diseases are rapidly increasing worldwide. Majority of these chronic ailments are curable, if diagnosed at early stages. Candidate biomarkers of early detection are therefore essential for identification of high-risk individuals, prompt and accurate disease diagnosis, and to monitor therapeutic response. The functional significance of circulating nucleic acids that recapitulate specific disease profiles is now well established. But subtle changes in DNA sequence may not solely reflect the differentiation of gene expression patterns observed in diverse set of diseases as epigenetic phenomena play a larger role in aetiology and patho-physiology. Unlike genetic markers, knowledge about the diagnostic utility of circulating epigenetic signatures: methylated DNA; micro RNA and modified histones are deficient. Characterization of these novel entities through omics-based molecular technologies might prompt development of a range of laboratory-based strategies, thereby accelerating their broader translational purpose for early disease diagnosis, monitoring therapeutic response and drug resistance. However, largest opportunity for innovation lies in developing point-of-care tests with accurate diagnostic and higher prognostic score that is applicable for screening of high-risk populations.

Hypersensitivity pneumonitis (HP), an immune-mediated subtype of interstitial lung diseases (ILDs), is mediated by repetitive inhalation of certain antigens. Transcriptomic signatures, which provide insight into the genetic alterations associated with a disease, somehow remain obscure for HP. In this study, unique transcriptome fingerprints associated with the pathogenesis of HP were investigated using systems biology approach. Furthermore, the metabolic signatures identified in our earlier study, were correlated with the differentially expressed genes (DEGs) to explore the integrated pathways. Two datasets (GSE150910 and GSE19314) procured from the Gene Expression Omnibus repository were used to identify the DEGs of HP patients. The enriched biological processes, altered pathways and protein-protein interaction (PPI) network associated with the DEGs were determined. Based on topological algorithms, 12 hub genes were screened; among which chemokine (C-X-C motif) ligand 13 (CXCL13), CXCL9and ribosomal protein large 36A (RPL36A) were identified as the top-ranked hub genes. The expression levels of these three candidate genes were experimentally validated in an HP patient cohort using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The findings indicated a trend similar to that of the bioinformatics observations. We integrated the metabolic signatures identified earlier with these hub genes and found glycolysis and phosphatidylinositol-3-kinase (PI3K/AKT) pathways to be impaired in these patients. Finally, the drug-gene interaction database DGIdb 4.0 indicated rituximab to be a promising drug for the management of HP. The present study is the first of its kind to combine bioinformatics and experimental data to identify and validate the genetic signatures and downstream pathways associated with HP. Our findings open up a new window to probe into the gene-metabolite crosstalk involved in the pathogenesis of HP and highlight promising therapeutic strategies.

Endometriosis is a common chronic estrogen-dependent gynecological disease affecting 10% of women in their reproductive age. It is characterized by proliferation of functional endometrial glands and stroma outside the uterine cavity. In the present study, we used mass spectrometry-based lipidomics to investigate the alterations in serum lipid profiles of mice induced with endometriosis. We identified several dysregulated lipids such as phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, and triglycerides and show that triglycerides may be due to a general inflammatory condition in the peritoneum. We also show that in addition to phosphatidylcholine alteration, there is also an effect in the ratio of phosphatidylcholine/phosphatidylethanolamine in serum of mice induced with the disease and that this change may be due to increased expression of the phosphatidylethanolamine N-methyltransferase gene. The study provides new insight into the etiology of endometriosis.

The present work focuses on the development of biodegradable PLGA nanoparticles (NPs) for controlled release of a breast cancer drug, letrozole. NPs of different drug-polymer ratio formulations (F1, F2, F3, F4) were fabricated using solvent evaporation technique. Physico-chemical characteristics of these NPs were assessed using dynamic light scattering (DLS) spectrophotometer. In-vitro drug release study was carried out over an extended period of 30 days at 37 °C in simulated physiological fluid. To evaluate the release kinetics, data was fitted to different models. NPs with various sizes and size distributions were obtained by altering the drug-polymer ratio. Zeta potential of PLGA and drug loaded NPs were found to be-29.4± 1.3 mV and-21.0±0.6 mV, respectively. The release kinetics of the drug from NPs was in good agreement with Korsmeyer-Peppas model, ensuring controlled release of the drug from the NPs. In-vitro release studies showed high correlation coefficient (R2 = 0.90) for formulation F2 and F3 up to 30 days. It is concluded that NPs with F2 and F3 formulations provide a controlled release of the incorporated drug and, therefore, hold promise to be investigated further in detail.

Hen egg white lysozyme (HEWL) adopts a molten globule-like state at high pH (~12.75) and is found to form amyloid fibrils at alkaline pH. Here, we report that Cu(II) inhibits self-association of HEWL at pH 12.75 both at 37 and 65 °C. A significant reduction in Thioflavin T fluorescence intensity, attenuation in β-sheet content and reduction in hydrophobic exposure were observed with increasing Cu(II) stoichiometry. Electron paramagnetic resonance spectroscopy suggests a 4N type of coordination pattern around Cu(II) during fibrillation. Cu(II) is also capable of altering the cytotoxicity of the proteinaceous aggregates. Fibrillar species of diverse morphology were found in the absence of Cu(II) with the generation of amorphous aggregates in the presence of Cu(II), which are more toxic compared to the fibrils alone.

In an attempt to find out the association of metabolic dysregulation with poor endometrial receptivity and pregnancy loss, serum metabonomic profiling of women with idiopathic recurrent spontaneous miscarriage (IRSM) is carried out and compared with fertile controls. 1H nuclear magnetic resonance (NMR)-based metabonomics was used to obtain serum metabolic profiles of 36 women with IRSM and 28 proven fertile women during the window of implantation. The acquired data were analyzed using multivariate principal component analysis, partial least-squares-discriminant analysis, and orthogonal projection to latent structure with discriminant analysis. A clear metabolic differentiation was evident between IRSM and control samples. The distinguishing metabolites, l-lysine, l-arginine, l-glutamine, l-histidine, l-threonine, l-phenylalanine, and l-tyrosine are significantly up-regulated in IRSM as compared to controls. These altered metabolites may be involved in the molecular mechanism of exaggerated inflammatory response and vascular dysfunction associated with poor endometrial receptivity in women with IRSM. The present work proposes a vital association of metabolic dysfunction with the disease pathogenesis.