Bio-Inspired Sensory Receptors for Artificial-Intelligence Perception.

In the era of artificial intelligence (AI), there is a growing interest in replicating human sensory perception. Selective and sensitive bio-inspired sensory receptors with synaptic plasticity have recently gained significant attention in developing energy-efficient AI perception. Various bio-inspired sensory receptors and their applications in AI perception are reviewed here. The critical challenges for the future development of bio-inspired sensory receptors are outlined, emphasizing the need for innovative solutions to overcome hurdles in sensor design, integration, and scalability. AI perception can revolutionize various fields, including human-machine interaction, autonomous systems, medical diagnostics, environmental monitoring, industrial optimization, and assistive technologies. As advancements in bio-inspired sensing continue to accelerate, the promise of creating more intelligent and adaptive AI systems becomes increasingly attainable, marking a significant step forward in the evolution of human-like sensory perception.

Effect of extracellular matrices on production and potency of mesenchymal stem cell-derived exosomes.

Mesenchymal stem cell (MSC) derived exosomes have emerged as potential acellular therapeutics for various tissue regenerative applications. However, successful clinical translation of exosome-based therapy is limited by lack of a structured production platform. Thus, in this study, the effect of decellularized extracellular matrix (dECM) was assessed on the production and potency of exosomes secreted by bone marrow-derived human MSCs. The results indicate that there was a ∼2-fold increase in MSC-exosome production when MSCs were cultured on dECM compared to TCP. Further, our study revealed that dECM generation induced by ascorbic acid (AA) up to 100 µg mL-1 highly increased exosome yield thereby indicating a potential scale up method for MSC exosome production. The bioactivity of exosomes was investigated by their ability to improve the healing of wounded human skin explants. Wound closure was enhanced in the presence of exosomes isolated from MSCs cultured on ascorbic acid-induced dECM compared to TCP generated MSC-exosomes. In summary, this study suggests a promising solution to a major bottleneck in large-scale production of MSC exosomes for cell-free therapy.

Investigating the Interplay Between Matrix Compliance and Passaging History on Chondrogenic Differentiation of Mesenchymal Stem Cells Encapsulated Within Alginate-Gelatin Hybrid Hydrogels.

Mesenchymal stem cells (MSCs) are used widely in tissue engineering and regenerative medicine because of their ease of isolation and their pluripotency. The low survival and retention rate of MSCs at the target site upon implantation can be addressed via encapsulation within hydrogels capable of directing their fate. In this study, the interplay between matrix mechanics and the passage number of MSCs on their chondrogenic differentiation was assessed. Human bone marrow-derived MSCs between passages 4 and 6 were encapsulated within alginate-gelatin hybrid gels. The stiffness of the gels was varied by varying alginate concentrations while maintaining the concentration of gelatin and consequently, the cell adhesion sites, constant. The study revealed that within 4.8 kPa gels, GAG deposition was higher by P4 MSCs compared to P6 MSCs. However, an opposite trend was observed with collagen type 2 deposition. Further, we observed enhanced chondrogenic differentiation upon encapsulation of MSCs within 6.7 kPa hydrogel irrespective of passaging history. However, the effect of matrix compliance was more prominent in the case of higher passaged MSCs suggesting that matrix stiffness can help rescue the reduced differentiation capability of these cells.

Role of mi RNA in Phytoremediation of Heavy Metals and Metal Induced Stress Alleviation.

Anthropogenic activities have contributed hugely in enhancing various types of environmental toxicity. One of these is higher accumulation of toxic heavy metals in soil and plant tissues. Although many heavy metals act as essential component for the growth and development of plants when present in low concentrations but at higher concentrations it becomes cytotoxic. Several innate mechanisms have evolved in plants to cope with it. In recent years the mechanism of using miRNA to combat metal induced toxicity has come to fore front. The miRNA or the microRNA regulates different physiological processes and induces a negative control in expressing the complementary target genes. The cleavage formation by post-transcriptional method and the inhibition of targeted translational mRNA are the two main procedures by which plant miRNAs function. The heavy and enhanced metal accumulation in plants has increased the production of different kinds of free radicals like reactive nitrogen and oxygen which damage the plants oxidatively. Several plant miRNA are capable of targeting and reducing the expression of those genes which are responsible for higher metal accumulation and storage. This can reduce the metal load and hence its negative impact on plant can also be reduced. This review depicts the biogenesis, the mode of action of miRNA, and the control mechanisms of miRNA in metal induced stress response in plant. A detailed review on the role of plant miRNA in alleviation of metal induced stress is discussed in this present study.

Fluorescence-Enhanced Microfluidic Biosensor Platform Based on Magnetic Beads with Highly Stable ZnO Nanorods for Biomarker Detection.

Existing affinity-based fluorescence biosensing systems for monitoring of biomarkers often utilize a fixed solid substrate immobilized with capture probes limiting their use in continuous or intermittent biomarker detection. Furthermore, there have been challenges of integrating fluorescence biosensors with a microfluidic chip and low-cost fluorescence detector. Herein, we demonstrated a highly efficient and movable fluorescence-enhanced affinity-based fluorescence biosensing platform that can overcome the current limitations by combining fluorescence enhancement and digital imaging. Fluorescence-enhanced movable magnetic beads (MBs) decorated with zinc oxide nanorods (MB-ZnO NRs) were used for digital fluorescence-imaging-based aptasensing of biomolecules with improved signal-to-noise ratio. High stability and homogeneous dispersion of photostable MB-ZnO NRs were obtained by grafting bilayered silanes onto the ZnO NRs. The ZnO NRs formed on MB significantly improved the fluorescence signal up to 2.35 times compared to the MB without ZnO NRs. Moreover, the integration of a microfluidic device for flow-based biosensing enabled continuous measurements of biomarkers in an electrolytic environment. The results showed that highly stable fluorescence-enhanced MB-ZnO NRs integrated with a microfluidic platform have significant potential for diagnostics, biological assays, and continuous or intermittent biomonitoring.

Drugs for COVID-19 Treatment: A New Challenge.

COVID-19 infection is a new disease and our knowledge is limited; day in and day out more and more interesting yet diverse observations are reported by the different research groups from different corners of the world. So, there is an urgent requirement of the invention of some effective and efficient drugs that can carry out the end of the deadly viral infection. Throughout the world, there have been many efforts carried out in different labs to invent such a drug and also identifying any pre-existing drugs which can carry out the killing of the virus. In this review, an effort has been made to understand the potential drugs which can be used against the SARS-CoV-2 viral infection. Again, the strategies on the current and the future drug discovery mechanisms against the SARS-CoV-2 are also mentioned. The different drugs made and the drugs re-used and also the drugs which are in the making process in different research laboratories across the world are also mentioned. To combat this unexpected crisis, we still need some more efforts from the different scientific communities around the world for finding a cure against this viral infection and this is needed to be done for the prevention of more loss of human life.

Progeria-a Rare Genetic Condition with Accelerated Ageing Process.

Progeria is a rare genetic disease which is characterised by accelerated ageing and reduced life span. There are differing types of progeria, but the classic type is Hutchinson-Gilford progeria syndrome (HGPS). Within a year of birth, people suffering from it start showing several features such as very low weight, scleroderma, osteoporosis and loss of hair. Their life expectancy is highly reduced and the average life span is around 14.6 years. Research is going on to understand the genetic and molecular level causes of this disease. Apart from that, several studies are also going on to discover therapeutic techniques and drugs to treat this disease but the success rate is very low. To gain a better understanding about research developments of progeria more experimental models, drugs and molecular technologies are under trial. Different important aspects and recent developments in epidemiology, genetic causes, symptoms, diagnosis and treatment options of progeria are discussed in this review.

The Role of Bystander Effect in Ultraviolet A Induced Photoaging.

Exposure to sunlight, mainly UVA, leads to typical changes in the features of the skin known as photoaging. UVA irradiation induces the expression of proteases that are responsible for the degradation of the extracellular matrix proteins to results in photoaging; it also downregulates the expression of proteins that are needed for the skin structure. Since, it is known that cells in the neighborhood of irradiated cells, but not directly exposed to it, often manifest responses like their irradiated counterparts, it is important to evaluate if these bystander cells too, can contribute to photoaging. UVA induced cell cycle arrest has been associated with photoaging, from flow cytometry analysis we found that there was an induction of cell cycle arrest at the G1/S phase in the UVA-bystander cells. The expression of some key photoaging marker genes likes, matrix metalloproteinases (MMP-1, MMP-3, MMP-9), cyclooxygenase-2 (COX-2), collagen1 and elastin were assessed from qRT-PCR. Up-regulation of MMP-1 and COX-2, downregulation of collagen1 and elastin, along with suppression below normal expression for MMP-3 and MMP-9 was observed in the UVA-bystander A375 cells. Our findings suggest that UVA-bystander cells may contribute to the process of photoaging.

Engineering tumor constructs to study matrix-dependent angiogenic signaling of breast cancer cells.

Breast cancer is the leading cause of cancer deaths among females globally. The crosstalk between tumor microenvironment and neoplastic cells is the key for promoting tumor growth, stimulating tumor angiogenesis, and metastasis to distant organs. Thus, it is highly important to investigate tumor cell-matrix interactions to facilitate screening of different anti-cancer agents, individually or in combination. We, herein report, the development of an in vitro three-dimensional (3D) breast cancer model to investigate the effect of stromal crosslinking and consequent, stiffening on the angiogenic activity of cancer cells. Crosslinking of collagen gels was altered via non-enzymatic glycation and highly aggressive breast cancer cells, MDA-MB-231, were encapsulated in these gels. Cells encapsulated in glycated/stiffer matrices displayed an increased expression of pro-angiogenesis-related signals. Inhibition of mechanotransduction pathways on the angiogenic activity of aggressive tumor cells in stiff matrices was investigated using Y-27632, blebbistatin, and cytochalasin D. Rho-associated kinase (ROCK) inhibitor, Y-27632, diminished the pro-angiogenic signaling, thereby suggesting the potential dependence of breast cancer cells on the Rho/ROCK pathway in regulating tumor angiogenesis. Our findings highlight the potential of the developed model to be used as a tool to investigate matrix-associated tumor angiogenesis and screen different therapeutic agents towards inhibiting it.

Poly C Binding Protein 2 dependent nuclear retention of the utrophin-A mRNA in C2C12 cells.

Upregulation of utrophin, the autosomal homologue of dystrophin, can compensate dystrophin deficiency in Duchenne Muscular Dystrophy (DMD) although the therapeutic success is yet to be achieved. The present study has identified Poly (C) binding protein 2 (PCBP2) as a post-transcriptional suppresser for the expression of utrophin-A, the muscle-specific utrophin isoform. This study confirms nuclear retention of utrophin-A mRNA in C2C12 cells, which is mediated by PCBP2. Further investigation demonstrates PCBP2-dependent nuclear retention of follistatin mRNA as well. Its involvement in nuclear retention of mRNA sheds light on a novel function of PCBP2 that makes utrophin-A mRNA less available in cytosol. PCBP2, therefore, may be a target to de-repress utrophin-A expression in DMD.

A Composite Microfiber for Biodegradable Stretchable Electronics.

Biodegradable stretchable electronics have demonstrated great potential for future applications in stretchable electronics and can be resorbed, dissolved, and disintegrated in the environment. Most biodegradable electronic devices have used flexible biodegradable materials, which have limited conformality in wearable and implantable devices. Here, we report a biodegradable, biocompatible, and stretchable composite microfiber of poly(glycerol sebacate) (PGS) and polyvinyl alcohol (PVA) for transient stretchable device applications. Compositing high-strength PVA with stretchable and biodegradable PGS with poor processability, formability, and mechanical strength overcomes the limits of pure PGS. As an application, the stretchable microfiber-based strain sensor developed by the incorporation of Au nanoparticles (AuNPs) into a composite microfiber showed stable current response under cyclic and dynamic stretching at 30% strain. The sensor also showed the ability to monitor the strain produced by tapping, bending, and stretching of the finger, knee, and esophagus. The biodegradable and stretchable composite materials of PGS with additive PVA have great potential for use in transient and environmentally friendly stretchable electronics with reduced environmental footprint.

Impact of mesenchymal stem cell-secretome-loaded hydrogel on proliferative and migratory activities of hyperglycemic fibroblasts.

Disruption of the reparative process, often found in diabetic patients, results in chronic, non-healing wounds that significantly impact a patient's quality of life. This highlights the need of new therapeutic options to improve the healing of diabetic wounds. In this study, we focused on developing a cell-free hydrogel dressing loaded with mesenchymal stem cell (MSC)-conditioned media (CM) to potentially improve the healing of hard-to-heal wounds. We simulated a hyperglycemic environment by incubating human dermal fibroblasts in a high glucose environment (30 mM) and validated that MSC-CM rescued the impaired functions (proliferation and migration) of hyperglycemic fibroblasts. Further, we investigated the effect of loading MSC-CM in gelatin methacrylate (GelMA)-poly (ethylene glycol) diacrylate (PEGDA) hybrid hydrogels in improving the proliferative activity of glucose-treated fibroblasts. The controlled release of bioactive factors from MSC-CM loaded GelMA-PEGDA hydrogels promoted the metabolic activity of hyperglycemic fibroblasts. In addition, the growth rate of hyperglycemic fibroblasts was found to be similar to that of normal fibroblasts. Our observations, thus, suggest the potential application of cell-free, MSC-secretome-loaded hydrogel in the healing of diabetic or chronic wounds.

9-phenyl acridine photosensitizes A375 cells to UVA radiation.

Acridines are an important class of bioactive molecules having varied uses. Its derivative, 9-phenylacridine (ACPH) had been found to exhibit antitumor activity both in cell lines and in vivo model. Its DNA binding ability and absorbance in the ultraviolet range encouraged us to investigate its role as a photosensitizer with UVA radiation. We investigated the effects of ACPH prior to UVA exposure on in vitro DNA through photo-cleavage assay. Effect of such treatment was also studied in cultured A375 melanoma cells. Endpoints studied included morphological changes, evaluation of cellular viability, scratch assay, intracellular reactive oxygen species (ROS) production, DNA damage, lipid peroxidation, glutathione (GSH) level, autophagy, cell cycle progression, depletion of mitochondrial membrane potential (ΔΨmt), induction of apoptosis and Hoechst dye efflux assay. Our findings indicated that ACPH could sensitize damage to DNA induced by UVA both in vitro and in cells. It could also potentiate cell killing by UVA. It arrested cells in G2/M phase and induced apoptotic death through mitochondria mediated pathway. This sensitization was through enhancement of intracellular ROS. Our findings also indicated that the stem cells side population was reduced on such treatment. The findings are important as it indicates ACPH as a promising photosensitizer and indicates its possible role in photodynamic therapy.

Harnessing mesenchymal stem cell secretome: Effect of extracellular matrices on proangiogenic signaling.

The low engraftment and retention rate of mesenchymal stem cells (MSCs) at the target site indicates that the potential benefits of MSC-based therapies can be attributed to their paracrine signaling. In this study, the extracellular matrices (ECMs) deposited by bone marrow-derived human MSCs in the presence and absence of ascorbic acid was characterized. MSCs were seeded on top of decellularized ECM (dECM) and the concentrations of proangiogenic and antiangiogenic molecules released in culture (conditioned) media was compared. Effects of ECM derived from MSCs with different passage numbers on MSC secretome was also investigated. Our study revealed that the expression of proangiogenesis-related factors were upregulated when MSCs were harvested on dECMs, irrespective of media supplementation, as compared with those cultured on tissue culture plates. In addition, dECM generated in the presence of ascorbic acid promoted the expression of proangiogenic molecules as compared with dECM-derived in absence of media supplementation. Further, it was observed that the effectiveness of dECM to stimulate proangiogenic signaling of MSCs was reduced as cell passage number was increased from P3 to P5. The proliferation as well as capillary morphogenesis of human umbilical vein endothelial cells (HUVECs) in the presence of conditioned media were enhanced compared with the normal HUVECs culture media. These data indicate that the secretory signatures of MSCs and consequently, the therapeutic efficacy of MSCs can be regulated by presentation of dECM composition and variation of its composition.

Study of arsenic (III) removal by monolayer protected silver nanoadsorbent and its execution on prokaryotic system.

This work deals with the removal of arsenic by nanoadsorbent from aqueous environment that is subsequently applied to the biological system for the evaluation of its efficiency. We started our aspiration by the modification of carboxylate functionalized silver nanoparticle (nanoadsorbent) fabrication process. Batch mode arsenic uptake study by the nanoadsorbent was conducted considering several altering parameters and the reactants in addition to products were evaluated by several analytical techniques for the interpretation of the interaction mechanism. It was found nanoadsorbent, Ag@MSA is an efficient system for the exclusion of arsenic (III) from the aqueous system and due to the alteration in the ratio of silver content and protective agent, the characteristic profile of silver nanoparticles with an average diameter of 15 nm also became changed in respect of reported results. Here the low pH range (4-6) favors the interaction between nanoparticle and arsenic and it was found that the interaction was chemical in nature through adsorption or complex formation with surface carboxylate groups of the protecting agent (MSA). Following the interaction, a successful removal of arsenic (III) was achieved at a percentage of 94.16 with an initial concentration of 45 mg/L and equilibrium time of 60 min. Hence nanoparticles were executed against the toxic effect of arsenic in E. coli, an important gut microbe of higher animals, for the restoration of bacterial growth in arsenic pre-removed media. In this context the validation of this removal efficiency against arsenic induced toxicity was proved through several morphological studies, degree of oxidative damages and other biochemical attributes.

Engineering microenvironments towards harnessing pro-angiogenic potential of mesenchymal stem cells.

Mesenchymal stem cell (MSC)-based therapy for promoting vascular regeneration is a promising strategy for treating ischemic diseases. However, low engraftment and retention rate of MSCs at the target site highlights the importance of paracrine signaling of MSCs in the reparative process. Thus, harnessing MSC-secretome is essential for rational design of MSC-based therapies. The role of microenvironment in regulating the paracrine signaling of MSCs is not well known. In this study, human bone marrow-derived MSCs were seeded on matrices with varying stiffness or cell adhesive sites, and conditioned media was collected. The concentrations of angiogenic molecules in the media was measured via ELISA. In addition, the bioactivity of the released molecules was investigated via assessing the proliferation and capillary morphogenesis of human umbilical vein endothelial cells (HUVECs) incubated with conditioned media. Our study revealed that secretion of vascular endothelial growth factor (VEGF) is dependent on substrate stiffness. Maximal secretion was observed when MSCs were seeded on hydrogel matrices of 5.0 kPa stiffness. Proliferation and tubulogenesis of HUVECs supported ELISA data. On the other hand, variation of cell adhesive sites while maintaining a uniform optimal stiffness, did not influence the pro-angiogenic activity of MSCs.

In Situ Synthesis of Silver Nanoparticles within Hydrogel-Conjugated Membrane for Enhanced Antibacterial Properties.

Biofouling negatively impacts water treatment performance of membranes by reducing water permeability, increasing energy consumption, and shortening the lifetime of the membranes. In this study, we integrated the bactericidal property of silver nanoparticles (AgNPs) with hydrophilicity of hydrogels to modify membranes that not only reduce adhesion, but also deactivate the adhered bacteria. Two approaches for AgNP synthesis were adopted-in situ synthesis and encapsulation in single step, and immobilization in multistep. Formation of AgNPs was confirmed by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD) studies. Compared to the pristine membrane, AgNP/hydrogel-modified membranes displayed no adverse effect in water flux under gravitational flow condition. The AgNP/hydrogel-modified membranes also exhibited better antibacterial properties (inhibition of adhesion and growth of Escherichia coli) as demonstrated by the bacterial growth, inhibition zone, and coculture (with the membranes) studies. The improvements could be attributed to the synergistic effect of hydrophilic hydrogel networks and the presence of bactericidal AgNPs. In addition, comparison of the antibacterial studies revealed the superiority of the encapsulated AgNPs over the immobilized AgNPs. This could be attributed to the efficient release of the former over the latter. To the best of our knowledge, this is the first study that demonstrates the enhancement of antibacterial properties of membrane via in situ synthesis and encapsulation of AgNPs within hydrogel matrices.

Investigation of Integrated Effects of Hydroxyapatite and VEGF on Capillary Morphogenesis of Endothelial Cells.

Major drawbacks of using autografts and allografts for repairing large bone defects/injuries are the shortage of available tissues and potential disease transmission. Bone tissue engineering is believed to be a promising alternative to bone grafts. The concomitant formation of vascular networks within the tissue engineered constructs for successful bone regeneration still remains a challenge. The physicochemical properties of a tissue microenvironment are known to regulate vascular network formation. However, our understanding of the mechanism, by which endothelial cells integrate these physicochemical signals emanating from the microenvironment to undergo capillary morphogenesis, is limited. In this study, the integrated effects of the vascular endothelial growth factor (VEGF), pro-angiogenic molecule, and hydroxyapatite (HA), widely used as an additive and a scaffold in bone reconstructive surgery, on capillary formation of human umbilical vein endothelial cells (HUVECs) were investigated. Toward this, HUVECs were seeded on scaffolds composed of 15% (w/v) poly(ethylene glycol) diacrylate, 5% (w/v) gelatin methacrylate (GelMA), and 1% (w/v) photoinitiator. The concentration of HA was varied from 0% to 0.2% (w/v). The study demonstrated that HA elicited an inhibitory response. The presence of VEGF promoted a sprouting response with a significant enhancement in the number of sprouts observed in the case of gels with higher concentrations of HA.

Hydrogel-based suspension array for biomarker detection using horseradish peroxidase-mediated silver precipitation.

Advances in medical diagnostics and personalized therapy require robust, sensitive yet cost-effective diagnostic tools for rapid measurement of biomolecules including proteins in body fluids. State-of-the-art technologies are complex and rely on expensive or custom made detection system, and therefore, cannot be readily adapted for point-of-care (POC) analysis. The development of a novel detection platform, which leverages horseradish peroxidase (HRP)-mediated silver precipitation within antibody immobilized porosity tuned poly (ethylene) glycol diacrylate (PEGDA) hydrogel microparticles with the operational advantages of suspension arrays for sensitive quantification of biomarkers, is described. In this study, vascular endothelial growth factor (VEGF) has been used as a model protein. The silver deposition corresponded to the concentration of VEGF in solution. The detection limit of 5.2 ± 1.0 pg/mL and assay time of 2 h highlights that this assay exceeds the conventional technologies in terms of sensitivity and speed. The practical applicability of the hydrogel microparticle based detection system has been established by demonstrating the ability of the system to quantify the production of VEGF by highly aggressive (MDA-MB-231) and non-aggressive (MCF-7) breast cancer cells. The reliance on simple instrument for quantification of clinically relevant markers bolsters the adaptability of the detection platform/method in POC settings.

Optimizing Multiplexed Detections of Diabetes Antibodies via Quantitative Microfluidic Droplet Array.

Sensitive, single volume detections of multiple diabetes antibodies can provide immunoprofiling and early screening of at-risk patients. To advance the state-of-the-art suspension assays for diabetes antibodies, porous hydrogel droplets are leveraged in microfluidic serpentine arrays to enhance reagent transport. This spatially multiplexed assay is applied to the detection of antibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2. Optimization of assay protocol results in a shortened assay time of 2 h, with better than 20 pg mL Supporting Information detection limits across all three antibodies. Specificity and cross-reactivity tests show negligible background, nonspecific antibody-antigen, and nonspecific antibody-antibody bindings. Multiplexed detections are able to measure within 15% of target concentrations from low to high ranges. The technique enables quantifications of as little as 8000 molecules in each 500 µm droplet in a single volume, multiplexed assay format, a breakthrough necessary for the adoption of diabetes panels for clinical screening and monitoring in the future.