Age-dependent genes in adipose stem and precursor cells affect regulation of fat cell differentiation and link aging to obesity via cellular and genetic interactions.

BACKGROUND: Age and obesity are dominant risk factors for several common cardiometabolic disorders, and both are known to impair adipose tissue function. However, the underlying cellular and genetic factors linking aging and obesity on adipose tissue function have remained elusive. Adipose stem and precursor cells (ASPCs) are an understudied, yet crucial adipose cell type due to their deterministic adipocyte differentiation potential, which impacts the capacity to store fat in a metabolically healthy manner. METHODS: We integrated subcutaneous adipose tissue (SAT) bulk (n=435) and large single-nucleus RNA sequencing (n=105) data with the UK Biobank (UKB) (n=391,701) data to study age-obesity interactions originating from ASPCs by performing cell-type decomposition, differential expression testing, cell-cell communication analyses, and construction of polygenic risk scores for body mass index (BMI). RESULTS: We found that the SAT ASPC proportions significantly decrease with age in an obesity-dependent way consistently in two independent cohorts, both showing that the age dependency of ASPC proportions is abolished by obesity. We further identified 76 genes (72 SAT ASPC marker genes and 4 transcription factors regulating ASPC marker genes) that are differentially expressed by age in SAT and functionally enriched for developmental processes and adipocyte differentiation (i.e., adipogenesis). The 76 age-perturbed ASPC genes include multiple negative regulators of adipogenesis, such as RORA, SMAD3, TWIST2, and ZNF521, form tight clusters of longitudinally co-expressed genes during human adipogenesis, and show age-based differences in cellular interactions between ASPCs and adipose cell types. Finally, our genetic data demonstrate that cis-regional variants of these genes interact with age as predictors of BMI in an obesity-dependent way in the large UKB, while no such gene-age interaction on BMI is observed with non-age-dependent ASPC marker genes, thus independently confirming our cellular ASPC results at the biobank level. CONCLUSIONS: Overall, we discover that obesity prematurely induces a decrease in ASPC proportions and identify 76 developmentally important ASPC genes that implicate altered negative regulation of fat cell differentiation as a mechanism for aging and directly link aging to obesity via significant cellular and genetic interactions.

Increased body mass index is linked to systemic inflammation through altered chromatin co-accessibility in human preadipocytes.

Obesity-induced adipose tissue dysfunction can cause low-grade inflammation and downstream obesity comorbidities. Although preadipocytes may contribute to this pro-inflammatory environment, the underlying mechanisms are unclear. We used human primary preadipocytes from body mass index (BMI) -discordant monozygotic (MZ) twin pairs to generate epigenetic (ATAC-sequence) and transcriptomic (RNA-sequence) data for testing whether increased BMI alters the subnuclear compartmentalization of open chromatin in the twins' preadipocytes, causing downstream inflammation. Here we show that the co-accessibility of open chromatin, i.e. compartmentalization of chromatin activity, is altered in the higher vs lower BMI MZ siblings for a large subset ( ~ 88.5 Mb) of the active subnuclear compartments. Using the UK Biobank we show that variants within these regions contribute to systemic inflammation through interactions with BMI on C-reactive protein. In summary, open chromatin co-accessibility in human preadipocytes is disrupted among the higher BMI siblings, suggesting a mechanism how obesity may lead to inflammation via gene-environment interactions.

Cross-Tissue Single-Nucleus RNA Sequencing Discovers Tissue-Resident Adipocytes Involved in Propanoate Metabolism in the Human Heart.

BACKGROUND: Adipocytes are crucial regulators of cardiovascular health. However, not much is known about gene expression profiles of adipocytes residing in nonfat cardiovascular tissues, their genetic regulation, and contribution to coronary artery disease. Here, we investigated whether and how the gene expression profiles of adipocytes in the subcutaneous adipose tissue differ from adipocytes residing in the heart. METHODS: We used single-nucleus RNA-sequencing data sets of subcutaneous adipose tissue and heart and performed in-depth analysis of tissue-resident adipocytes and their cell-cell interactions. RESULTS: We first discovered tissue-specific features of tissue-resident adipocytes, identified functional pathways involved in their tissue specificity, and found genes with cell type-specific expression enrichment in tissue-resident adipocytes. By following up these results, we discovered the propanoate metabolism pathway as a novel distinct characteristic of the heart-resident adipocytes and found a significant enrichment of coronary artery disease genome-wide association study risk variants among the right atrium-specific adipocyte marker genes. Our cell-cell communication analysis identified 22 specific heart adipocyte-associated ligand-receptor pairs and signaling pathways, including THBS (thrombospondin) and EPHA (ephrin type-A), further supporting the distinct tissue-resident role of heart adipocytes. Our results also suggest chamber-level coordination of heart adipocyte expression profiles as we observed a consistently larger number of adipocyte-associated ligand-receptor interactions and functional pathways in the atriums than ventricles. CONCLUSIONS: Overall, we introduce a new function and genetic link to coronary artery disease for the previously unexplored heart-resident adipocytes.

Cross-tissue omics analysis discovers ten adipose genes encoding secreted proteins in obesity-related non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a fast-growing, underdiagnosed, epidemic. We hypothesise that obesity-related inflammation compromises adipose tissue functions, preventing efficient fat storage, and thus driving ectopic fat accumulation into the liver. METHODS: To identify adipose-based mechanisms and potential serum biomarker candidates (SBCs) for NAFLD, we utilise dual-tissue RNA-sequencing (RNA-seq) data in adipose tissue and liver, paired with histology-based NAFLD diagnosis, from the same individuals in a cohort of obese individuals. We first scan for genes that are differentially expressed (DE) for NAFLD in obese individuals' subcutaneous adipose tissue but not in their liver; encode proteins secreted to serum; and show preferential adipose expression. Then the identified genes are filtered to key adipose-origin NAFLD genes by best subset analysis, knockdown experiments during human preadipocyte differentiation, recombinant protein treatment experiments in human liver HepG2 cells, and genetic analysis. FINDINGS: We discover a set of genes, including 10 SBCs, that may modulate NAFLD pathogenesis by impacting adipose tissue function. Based on best subset analysis, we further follow-up on two SBCs CCDC80 and SOD3 by knockdown in human preadipocytes and subsequent differentiation experiments, which show that they modulate crucial adipogenesis genes, LPL, SREBPF1, and LEP. We also show that treatment of the liver HepG2 cells with the CCDC80 and SOD3 recombinant proteins impacts genes related to steatosis and lipid processing, including PPARA, NFE2L2, and RNF128. Finally, utilizing the adipose NAFLD DE gene cis-regulatory variants associated with serum triglycerides (TGs) in extensive genome-wide association studies (GWASs), we demonstrate a unidirectional effect of serum TGs on NAFLD with Mendelian Randomization (MR) analysis. We also demonstrate that a single SNP regulating one of the SBC genes, rs2845885, produces a significant MR result by itself. This supports the conclusion that genetically regulated adipose expression of the NAFLD DE genes may contribute to NAFLD through changes in serum TG levels. INTERPRETATION: Our results from the dual-tissue transcriptomics screening improve the understanding of obesity-related NAFLD by providing a targeted set of 10 adipose tissue-active genes as new serum biomarker candidates for the currently grossly underdiagnosed fatty liver disease. FUNDING: The work was supported by NIH grants R01HG010505 and R01DK132775. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The KOBS study (J. P.) was supported by the Finnish Diabetes Research Foundation, Kuopio University Hospital Project grant (EVO/VTR grants 2005-2019), and the Academy of Finland grant (Contract no. 138006). This study was funded by the European Research Council under the European Union's Horizon 2020 research and innovation program (Grant No. 802825 to M. U. K.). K. H. P. was funded by the Academy of Finland (grant numbers 272376, 266286, 314383, and 335443), the Finnish Medical Foundation, Gyllenberg Foundation, Novo Nordisk Foundation (grant numbers NNF10OC1013354, NNF17OC0027232, and NNF20OC0060547), Finnish Diabetes Research Foundation, Finnish Foundation for Cardiovascular Research, University of Helsinki, and Helsinki University Hospital and Government Research Funds. I. S. was funded by the Instrumentarium Science Foundation. Personal grants to U. T. A. were received from the Matti and Vappu Maukonen Foundation, Ella och Georg Ehrnrooths Stiftelse and the Finnish Foundation for Cardiovascular Research.

Identification of Common Dysregulated Genes in COVID-19 and Hypersensitivity Pneumonitis: A Systems Biology and Machine Learning Approach.

A comprehensive knowledge on systems biology of severe acute respiratory syndrome coronavirus 2 is crucial for differential diagnosis of COVID-19. Interestingly, the radiological and pathological features of COVID-19 mimic that of hypersensitivity pneumonitis (HP), another pulmonary fibrotic phenotype. This motivated us to explore the overlapping pathophysiology of COVID-19 and HP, if any, and using a systems biology approach. Two datasets were obtained from the Gene Expression Omnibus database (GSE147507 and GSE150910) and common differentially expressed genes (DEGs) for both diseases identified. Fourteen common DEGs, significantly altered in both diseases, were found to be implicated in complement activation and growth factor activity. A total of five microRNAs (hsa-miR-1-3p, hsa-miR-20a-5p, hsa-miR-107, hsa-miR-16-5p, and hsa-miR-34b-5p) and five transcription factors (KLF6, ZBTB7A, ELF1, NFIL3, and ZBT33) exhibited highest interaction with these common genes. Next, C3, CFB, MMP-9, and IL1A were identified as common hub genes for both COVID-19 and HP. Finally, these top-ranked genes (hub genes) were evaluated using random forest classifier to discriminate between the disease and control group (coronavirus disease 2019 [COVID-19] vs. controls, and HP vs. controls). This supervised machine learning approach demonstrated 100% and 87.6% accuracy in differentiating COVID-19 from controls, and HP from controls, respectively. These findings provide new molecular leads that inform COVID-19 and HP diagnostics and therapeutics research and innovation.

Optoelectronic Trajectory Reconfiguration and Directed Self-Assembly of Self-Propelling Electrically Powered Active Particles.

Self-propelling active particles are an exciting and interdisciplinary emerging area of research with projected biomedical and environmental applications. Due to their autonomous motion, control over these active particles that are free to travel along individual trajectories, is challenging. This work uses optically patterned electrodes on a photoconductive substrate using a digital micromirror device (DMD) to dynamically control the region of movement of self-propelling particles (i.e., metallo-dielectric Janus particles (JPs)). This extends previous studies where only a passive micromotor is optoelectronically manipulated with a translocating optical pattern that illuminates the particle. In contrast, the current system uses the optically patterned electrode merely to define the region within which the JPs moved autonomously. Interestingly, the JPs avoid crossing the optical region's edge, which enables constraint of the area of motion and to dynamically shape the JP trajectory. Using the DMD system to simultaneously manipulate several JPs enables to self-assemble the JPs into stable active structures (JPs ring) with precise control over the number of participating JPs and passive particles. Since the optoelectronic system is amenable to closed-loop operation using real-time image analysis, it enables exploitation of these active particles as active microrobots that can be operated in a programmable and parallelized manner.

Posterior reversible encephalopathy syndrome following coronary angiography.

Posterior reversible encephalopathy syndrome (PRES) is a relatively rare neurotoxic disorder. A 56-year-old male underwent elective coronary angiography. A Few hours postprocedure, the patient developed bilateral painless vision loss, headache, vomiting and hypertension and was subsequently diagnosed with PRES. Possible trigger factors could be contrast agent used, or hypertension. Contrast agent-induced PRES in hypertensive patients is benign and reversible, and a high-grade suspicion about this possibility is critical for precise management. Our patient was successfully treated with supportive management and was doing well on follow-up.

Outcomes of urgent coronary artery bypass grafting in patients who have recently recovered from COVID-19 infection, with a median follow-up period of twelve months: our experience.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) was declared a worldwide pandemic in 2020 by the World Health Organization (WHO). Certain individuals are at higher risk, (age > 65 years, pre-existing lung or heart conditions, diabetes and obesity) especially those requiring cardiac surgery, including Coronary Artery Bypass Grafting (CABG). Here we present a case series of 11 patients, operated between April 2020 and April 2022, all of whom had recently recovered from COVID-19, who presented with unstable angina, and therefore required urgent Coronary Artery Bypass Grafting (CABG). Similar cases reported in the past, have had a high morbidity and mortality rate. CASE PRESENTATION: The study included 11 males, and their age varied between 53 and 68 years (median of 65 years). They were either partially or fully vaccinated. All of them had a history of recent mild COVID-19 infection. The European system for cardiac operative risk evaluation, EuroSCORE II in-hospital mortality risk at admission, varied between 1.48% and 5.12%. Six out of 11 patients (54.55%) had a recent Acute Coronary Syndrome (ACS) which is associated with a higher risk and poor prognosis. All of them underwent urgent CABG (10 of them, 90.91% cases, using the off-pump technique and one patient had to be converted to the on-pump beating heart surgery technique during surgery). Ten of the 11 patients were operated using the off-pump technique, and there was one death (9.09%). All surviving patients made an uneventful recovery and have been followed up with a median follow-up period of 12 months. CONCLUSIONS: Previous studies on a similar group of patients have resulted in high morbidity and mortality. A conscious effort was made to perform all surgeries off-pump, thereby eliminating the inflammatory effects and other hazards of cardiopulmonary bypass in this case series, with only one out of 11 (9.09%) being converted to the on-pump beating heart technique due to the hemodynamic instability faced during surgery. Our findings show a mortality rate of 9.09%, with the surviving patients doing well at a median follow-up period of 12 months, suggesting that it is a safe procedure in this patient subset.

COVID-19 presenting after Elective Off-pump Coronary Artery Bypass Grafting and Lessons Learned.

BACKGROUND: Cases of COVID-19 presenting after elective cardiac surgery are rare. Published literature suggests that such cases have a high morbidity and mortality rate. Here, we report a case of COVID-19 presenting after an elective, isolated off-pump coronary artery bypass (OPCAB). CASE PRESENTATION: A 65-year-old obese, hypertensive, hypothyroid lady, with moderate left ventricular dysfunction, presenting with unstable angina, tested negative for COVID-19 at admission, having undergone thrombolysis for a recent inferior wall myocardial infarction, at an outside centre, and coronary angiography revealing left main triple vessel disease, developed signs and symptoms of COVID-19, four days after OPCAB. She was diagnosed with moderate COVID-19 infection. Subsequent contact tracing revealed that her husband was suffering from mild COVID-19 infection and was managed in home isolation. Isolation and early supportive management with moist oxygen, steroids, intravenous antibiotics, zinc and vitamin C helped the patient recover. She was followed up at one month, six months, one year and at eighteen months and has been doing well. CONCLUSIONS: A strong clinical suspicion and repeat testing for COVID-19 is required as the diagnosis may often be missed with COVID-19 mimicking the signs and symptoms of post-cardiotomy syndrome. Preferentially dealing with such cases off-pump, thereby avoiding cardio pulmonary bypass-related complications, may improve outcomes. Isolation and early supportive management help. Adequate follow-up is required in all such cases as cardiovascular complications are common, alongside known long-term sequelae, like anxiety, depression, cardio-respiratory complications, venous thromboembolism and even postural orthostatic tachycardia syndrome.

Switching from Chemical to Electrical Micromotor Propulsion across a Gradient of Gastric Fluid via Magnetic Rolling.

To address and extend the finite lifetime of Mg-based micromotors due to the depletion of the engine (Mg-core), we examine electric fields, along with previously studied magnetic fields, to create a triple-engine hybrid micromotor for driving these micromotors. Electric fields are a facile energy source that is not limited in its operation time and can dynamically tune the micromotor mobility by simply changing the frequency and amplitude of the field. Moreover, the same electrical fields can be used for cell trapping and transport as well as drug delivery. However, the limitations of these propulsion mechanisms are the low pH (and high conductivity) environment required for Mg dissolution, while the electrical propulsion is quenched at these conditions as it requires low conductivity mediums. In order to translate the micromotor between these two extreme medium conditions, we use magnetic rolling as means of self-propulsion along with magnetic steering. Interestingly, electrical propulsion also necessitates at least the partial consumption of the Mg, resulting in a sufficient geometrical asymmetry of the micromotor. We have successfully demonstrated the rapid propulsion switching capability of the micromotor, from chemical to electrical motions, via magnetic rolling within a microfluidic device with the concentration gradient of the simulated gastric fluid. Such triple-engine micromotor propulsion holds considerable promise for in vitro studies mimicking gastric conditions and performing various bioassay tasks.

Vessel wall calcification and vascular event: Are we concerned enough?

A 49-year-old lady, hypertensive with dyslipidaemia, had thalamic bleed with intracranial multiple micro-haemorrhages. An extensive search was done and vasculitis was ruled out in the patient. Henceforth, she remained strict with medications and maintained blood pressure and lipids under control. After a lucid interval of 3 years, she attended emergency with complex partial seizure. We detected extensive microbleeds (significant increment) in magnetic resonance imaging of the brain and periventricular ischemic changes. A cerebrospinal fluid study and digital subtraction angiography of the brain were consistent with primary central nervous system (CNS) vasculitis (small vessel). She improved and currently is well on follow-up with immunosuppressive therapy. Interesting learning part in our case was late presentation of the patient with primary CNS vasculitis after a latency. It implies requirement of strong suspicion and stringent follow-up in these types of patients.

Non-wetting Liquid-Infused Slippery Paper.

Liquid-infused slippery surfaces have replaced structural superhydrophobic surfaces in a plethora of emerging applications, hallmarked by their favorable self-healing and liquid-repelling characteristics. Their ease of fabrication on different types of materials and increasing demand in various industrial applications have triggered research interests targeted toward developing an environmental-friendly, flexible, and frugal substrate as the underlying structural and functional backbone. Although many expensive polymers such as polytetrafluoroethylene have so far been used for their fabrication, these are constrained by their compromised flexibility and non-ecofriendliness due to the use of fluorine. Here, we explore the development and deployment of a biodegradable, recyclable, flexible, and an economically viable material in the form of a paper matrix for fabricating liquid-infused slippery interfaces for prolonged usage. We show by controlled experiments that a simple silanization followed by an oil infusion protocol imparts an inherent slipperiness (low contact angle hysteresis and low tilting angle for sliding) to the droplet motion on the paper substrate and provides favorable anti-icing characteristics, albeit keeping the paper microstructures unaltered. This ensures concomitant hydrophobicity, water adhesion, and capillarity for low surface tension fluids, such as mustard oil, with an implicit role played by the paper pore size distribution toward retaining a stable layer of the infused oil. With demonstrated supreme anti-icing characteristics, these results open up new possibilities of realizing high-throughput paper-based substrates for a wide variety of applications ranging from biomedical unit operations to droplet-based digital microfluidics.

MicroRNA expression patterns in HbE/ß-thalassemia patients: The passwords to unlock fetal hemoglobin expression in ß-hemoglobinopathies.

Hemoglobin E (HbE)/ß-thalassemia is a form of ß-hemoglobinopathy that is well-known for its clinical heterogeneity. Individuals suffering from this condition are often found to exhibit increased fetal hemoglobin (HbF) levels - a factor that may contribute to their reduced blood transfusion requirements. This study hypothesized that the high HbF levels in HbE/ß-thalassemia individuals may be guided by microRNAs and explored their involvement in the disease pathophysiology. The miRNA expression profile of hematopoietic progenitor cells in HbE/ß-thalassemia patients was investigated and compared with that of healthy controls. Using miRNA PCR array experiments, eight miRNAs (hsa-miR-146a-5p, hsa-miR-146b-5p, hsa-miR-148b-3p, hsa-miR-155-5p, hsa-miR-192-5p, hsa-miR-335-5p, hsa-miR-7-5p, hsa-miR-98-5p) were identified to be significantly up-regulated whereas four miRNAs (hsa-let-7a-5p, hsa-miR-320a, hsa-let-7b-5p, hsa-miR-92a-3p) were significantly down-regulated. Target analysis found them to be associated with several biological processes and molecular functions including MAPK and HIF-1 signaling pathways - the pathways known to be associated with HbF upregulation. Results of dysregulated miRNAs further indicated that miR-17/92 cluster might be of critical importance in HbF regulation. The findings of our study thus identify key miRNAs that can be extrinsically manipulated to elevate HbF levels in ß-hemoglobinopathies.

Flow and deformation characteristics of a flexible microfluidic channel with axial gradients in wall elasticity.

Axial gradients in wall elasticity may have significant implications in the deformation and flow characteristics of a narrow fluidic conduit, bearing far-reaching consequences in physiology and bio-engineering. Here, we present a theoretical and experimental framework for fluid-structure interactions in microfluidic channels with axial gradients in wall elasticity, in an effort to arrive at a potential conceptual foundation for in vitro study of mirovascular physiology. Towards this, we bring out the static deformation and steady flow characteristics of a circular microchannel made of polydimethylsiloxane (PDMS) bulk, considering imposed gradients in the substrate elasticity. In particular, we study two kinds of elasticity variations - a uniformly soft (or hard) channel with a central strip that is hard (or soft), and, increasing elasticity along the length of the channel. The former kind yields a centrally constricted (or expanded) deformed profile in response to the flow. The latter kind leads to increasingly bulged channel radius from inlet to outlet in response to flow. We also formulate an analytical model capturing the essential physics of the underlying elastohydrodynamic interactions. The theoretical predictions match favourably with the experimental observations and are also in line with reported results on stenosis in mice. The present framework, thus, holds the potential for acting as a fundamental design basis towards developing in vitro models for micro-circulation, capable of capturing exclusive artefacts of healthy and diseased conditions.

Anomalous diffusion in an electrolyte saturated paper matrix.

Diffusion of colored dye on water saturated paper substrates has been traditionally exploited with great skill by renowned water color artists. The same physics finds more recent practical applications in paper-based diagnostic devices deploying chemicals that react with a bodily fluid yielding colorimetric signals for disease detection. During spontaneous imbibition through the tortuous pathways of a porous electrolyte saturated paper matrix, a dye molecule undergoes diffusion in a complex network of pores. The advancing front forms a strongly correlated interface that propagates diffusively but with an enhanced effective diffusivity. We measure this effective diffusivity and show that it is several orders of magnitude greater than the free solution diffusivity and has a significant dependence on the solution pH and salt concentration in the background electrolyte. We attribute this to electrically mediated interfacial interactions between the ionic species in the liquid dye and spontaneous surface charges developed at porous interfaces, and introduce a simple theory to explain this phenomenon.

Electro-kinetically driven route for highly sensitive blood pathology on a paper-based device.

Enhancing the sensitivity of colorimetric detection in paper-devices is a quintessential step in achieving frugal diagnosis. Here, we demonstrate an effective way of improving the detection sensitivity of paper-based devices, as mediated by electro-kinetic mechanisms. By directly employing blood plasma, we investigate the electro-kinetic clustering of glucose, a neutral molecule in paper devices. Under the influence of uniform electric field, dispersed glucose gets accumulated in the paper strips. Due to the combination of EOF and electrophoretic migration, we achieve twofold increase in the colour intensity for both normal and diabetic samples. This approach is robust and possesses better sensitivity than conventional colorimetric assays and can be easily extended to other body fluid based diagnosis. These results may turn out to be of profound importance in improving the quality of pathological diagnosis in low-cost paper-based point-of-care devices deployed in resource-limited settings.

Identification of deleterious SNPs and their effects on BCL11A, the master regulator of fetal hemoglobin expression.

The B-cell lymphoma/leukemia 11A protein (encoded by BCL11A gene) is a key regulator of fetal-to-adult hemoglobin switching as seen in post-natal life. Although genetic polymorphisms like SNPs in BCL11A gene are expected to affect fetal hemoglobin (HbF) expression levels, yet their implications are poorly studied. This study utilizes a computational approach to identify the deleterious SNPs which may affect the structure and function of BCL11A protein. The study also generated a 3D structure of native and mutants. The analysis identified two SNPs in BCL11A as highly deleterious: N391K and C414S which are expected to affect structure and stability of the protein. According to conservation analysis, both residues N391 and C414 were identified as highly conserved. Additionally, post-translational modification sites were predicted at both sites. Ligand binding sites were also predicted in N391 and C414. Therefore, N391K and C414S in BCL11A can considered as important candidates to mediate HbF variation.

Electrical Power Generation from Wet Textile Mediated by Spontaneous Nanoscale Evaporation.

Developing low-weight, frugal, and sustainable power sources for resource-limited settings appears to be a challenging proposition for the advancement of next-generation sensing devices and beyond. Here, we report the use of centimeter-sized simple wet fabric pieces for electrical power generation by deploying the interplay of a spontaneously induced ionic motion across fabric nanopores due to capillary action and simultaneous water evaporation by drawing thermal energy from the ambient. Unlike other reported devices with similar functionalities, our arrangement does not necessitate any input mechanical energy or complex topographical structures to be embedded in the substrate. A single device is capable of generating a sustainable open circuit potential up to ∼700 mV, which is further scaled up to ∼12 V with small-scale multiplexing (i.e., deploying around 40 numbers of fabric channels simultaneously). The device is able to charge a commercial supercapacitor of ∼0.1 F which can power a white light-emitting diode for more than 1 h. This suffices in establishing an inherent capability of functionalizing self-powered electronic devices and also to be potentially harnessed for enhanced power generation with feasible up-scaling.

Integrative microRNA and gene expression analysis identifies new drug repurposing candidates for fetal hemoglobin induction in ß-hemoglobinopathies.

Therapeutic induction of fetal hemoglobin (HbF) is one of the most promising approaches to ameliorate the severity of hemoglobinopathies like ß-thalassemia and sickle cell anemia. Although several pharmacological agents have been investigated for HbF induction in adults, the majority of these are associated with significant side-effects. While drug repurposing is known to open new doors for the use of approved drugs in unexplored clinical conditions, the primary challenge lies in identifying such candidates. In this study, we aimed to identify repurposing candidates for HbF induction using a novel in silico approach utilizing microRNA-pathway-drug relationships. A computational drug repurposing strategy identified several unique candidates for HbF induction; among which Curcumin, Ginsenoside, Valproate, and Vorinostat were found to be most suitable for future trials. This study identified new drug repurposing candidates for HbF induction and demonstrates an easily adaptable methodology that can be used for other pathophysiological conditions.