Terahertz binary computing in a coupled toroidal metasurface.

The applications of terahertz metamaterials are being actively explored in recent times for applications in high-speed communication devices, miniature photonic circuits, and bio-chemical devices because of their wide advantages. The toroidal resonance, a new type of metasurface resonance, has been examined with great interest to utilize its properties in terahertz metasurface applications. This study reports a proof of concept design of a toroidal metasurface that experimentally demonstrates binary computing operations in the terahertz frequency regime. The analog computing of binary operations is achieved by the passive tuning of distance between the split ring resonators comprising the meta-molecule. The amplitude modulation is utilized as a method of determining the Boolean logic outputs of the system. The proposed metasurface could be further optimized for high amplitude modulations and active logic gate operations using tunable materials including graphene and ITO. The proposed metasurface consists of three split-ring resonators, and the near-field coupling between the adjacent resonators dictates the Boolean operations. A multipole analysis of the scattered powers of terahertz radiation determines the toroidal excitation in the metasurface. The proposed metasurfaces experimentally define AND Boolean logic operation at 0.89 terahertz, and OR Boolean logic operation at 0.97 terahertz. Numerical simulations support the experimentally obtained results. Additionally, we numerically report the excitation of NAND operation at 0.87 THz. Such toroidal analog computing metasurfaces could find applications in digitized terahertz circuits and integrated photonic devices.

Invitro anti-biofilm activity and the artificial chaperone activity of quinoline-based ionic liquids.

The maintenance of protein conformation under stressful conditions is one of the prevailing challenges. This has led to a rapid growth in the ingenious protein therapies, in the past few decades, prioritizing the investigation of the structure and function of proteins in novel environments. Ionic Liquids (ILs) are currently dominating the biomedical industry, by endowing great solubility and stability to bio-molecules, especially proteins. Recently, researchers have devoted their attention towards the artificial chaperone activity of several classes of ILs. Thus, comprehending the long-term as well as momentary stability of protein conformation in IL formulations is an absolute necessity. In this context, we present the activity of quinoline-based ionic liquids (ILs) as artificial cheperones against time-dependent, self induced fibril formation in Bovine Serum Albumin (BSA). Herein, a series of quinoline-based ILs were synthesized and characterized. The structural and morphological changes induced in BSA in the presence and absence of these ILs are corroborated using several spectroscopic measurements and in-silico studies. The anti-microbial and antibiofilm activity of these compounds demonstrating their medicinal properties is substantiated in this study. Furthermore, the present research also gives an account of the toxicity of these compounds under in vivo conditions, using C. elegans as the model organism.

Mechanisms of antifungal resistance and developments in alternative strategies to combat Candida albicans infection.

Candida albicans is a commensal fungus that infects the humans and becomes an opportunistic pathogen particularly in immuno-compromised patients. Among the Candida genus, yeast C. albicans is the most frequently incriminated species and is responsible for nearly 50-90% of human candidiasis, with vulvovaginal candidiasis alone, affecting about 75% of the women worldwide. One of the significant virulence traits in C. albicans is its tendency to alternate between the yeast and hyphae morphotypes, accounting for the development of multi-drug resistance in them. Thus, a thorough comprehension of the decision points and genes controlling this transition is necessary, to understand the pathogenicity of this, naturally occurring, pernicious fungus. Additionally, the formation of C. albicans biofilm is yet another pathogenesis trait and a paramount cause of invasive candidiasis. Since 1980 and in 90 s, wide spread use of immune-suppressing therapies and over prescription of fluconazole, a drug used to treat chronic fungal infections, triggered the emergence of novel anti-fungal drug development. Thus, this review thoroughly elucidates the diseases associated with C. albicans infection as well as the anti-fungal resistance mechanism associated with them and identifies the emerging therapeutic agents, along with a rigorous discussion regarding the future strategies that can possibly be adopted for the cure of this deleterious pathogen.

Optical biosensors for environmental monitoring: Recent advances and future perspectives in bacterial detection.

The environmental contamination due to bacterial proliferation vs their identification is the major deciding factor in the spread of diseases leading to pandemics. The advent of drug-resistant pathogenic contaminants in our environment has further added to the load of complications associated with their diagnosis and treatment. Obstructing the spread of such infections, prioritizes the expansion of sensor-based diagnostics, effectuating, a sturdy detection of disease-causing microbes, contaminating our surroundings in shortest possible time, with minimal expenditure. Among many sensors known, optical biosensors promote the recognition of pathogens befouling the environment through a comparatively intuitive, brisk, portable, multitudinous, and thrifty approach. This article reviews the recent progresses in optical biosensor-based systems for effective environmental monitoring. The technical and methodological perspectives of fundamental optical-sensing platforms are reviewed, combined with the pros and cons of every procedure. Eventually, the obstacles lying in the path of development of an effective optical biosensor device for bio-monitoring and its future perspectives are highlighted in the present work.

Neural Stem Cell-based Regenerative Therapy: A New Approach to Diabetes Treatment.

Diabetes mellitus (DM) is the most common metabolic disorder that occurs due to the loss, or impaired function of insulin-secreting pancreatic beta cells, which are of two types - type 1 (T1D) and type 2 (T2D). To cure DM, the replacement of the destroyed pancreatic beta cells of islet of Langerhans is the most widely practiced treatment. For this, isolating neuronal stem cells and cultivating them as a source of renewable beta cells is a significant breakthrough in medicine. The functions, growth, and gene expression of insulin-producing pancreatic beta cells and neurons are very similar in many ways. A diabetic patient's neural stem cells (obtained from the hippocampus and olfactory bulb) can be used as a replacement source of beta cells for regenerative therapy to treat diabetes. The same protocol used to create functional neurons from progenitor cells can be used to create beta cells. Recent research suggests that replacing lost pancreatic beta cells with autologous transplantation of insulin-producing neural progenitor cells may be a perfect therapeutic strategy for diabetes, allowing for a safe and normal restoration of function and a reduction in potential risks and a long-term cure.

Thymol encapsulated chitosan-Aloe vera films for antimicrobial infection.

Wound healing is an extremely intricate process involving various potential factors that can contribute towards delayed healing, one of them being bacterial colonization. The current research addresses this issue through the development of herbal antimicrobial films that can be stripped off easily, formed using an essential oil component thymol, biopolymer chitosan, and herbal plant Aloe vera. In comparison to the conventionally used nanoemulsions, thymol encapsulated in chitosan-Aloe vera (CA) film exhibited high encapsulation efficiency (95.3 %) with alleviated physical stability, as established using a high zeta potential value. The pronounced loss of crystallinity, validated using X-ray diffractometry, combined with the results obtained from Infrared and Fluorescence spectroscopic analysis, confirmed the encapsulation of thymol in CA matrix through hydrophobic interactions. This encapsulation increases the spaces between biopolymer chains facilitating greater intrusion of water, conducive for preventing the possibility of bacterial infection. Antimicrobial activity was tested against various pathogenic microbes such as Bacillus, Staphylococcus, Escherichia, Pseudomonas, Klebsiella and Candida. Results showed potential antimicrobial activity in the prepared films. Release test was also run at 25 °C suggesting a two-step biphasic release mechanism. The encapsulated thymol had higher biological activity, as assessed by antioxidant DPPH assay, likely due to improved dispersibility.

An electrochemical impedance aptasensor based on selenomolybdate nanodot/antimonene hybrid for platelet-derived growth factor-BB.

The aim of the present study was to design a unique bioelectrode for the quantitative analysis of a potential cancer biomarker, platelet-derived growth factor-BB (PDGF-BB), which can be used for the early detection of cancer. We report the fabrication of succinic acid-capped selenomolybdate polyoxometalate nanodots, POM (SA), decorated antimonene hybrid film on glassy carbon as a suitable bioelectrode. Antimonene nanosheets, synthesized by the chemical exfoliation of antimony provided a large surface area for the symmetric dispersal of POM (SA) nanodots, resulting in site-specific covalent immobilization of the aptamer, PDGF-BB. A comprehensive electrochemical immunosensing investigation was performed on the electrode for sensing of a target antigen, Ag-PDGF-BB. The sensitivity, selectivity, and reproducibility of the bioelectrode were investigated using a best-fit equivalent circuit model that fitted the impedance response. The bioelectrode showed a linear impedimetric response in a broad range for Ag-PDGF-BB (10 pM to 100 nM in pH 7.4 PB) with a limit of detection of 3.5 pM and sensitivity of 80 Ω cm2 per decade. The response sensitivity of the POM(SA)/antimonene hybrid based bioelectrode toward PDGF-BB was approximately ∼1.8-fold higher than that of the POM(SA) only modified bioelectrode. The dissociation constant of immunoreaction between the aptamer-functionalized bioelectrode and target Ag-PDGF-BB was 76 nM, indicating a high binding affinity between the aptamer PDGF-BB and target Ag-PDGF-BB on the electrode surface.

Microfluidics Based Generation of Curcumin Loaded Microfibrous Mat against Staphylococcus aureus Biofilm by Photodynamic Therapy.

The rapid increase in multidrug resistant biofilm infections is a major concern for global health. A highly effective therapy is required for the treatment of biofilm related infections. In this study, curcumin loaded alginate microfibers were generated by using the microfluidic technique. In this strategy, alginate microfibers are used as a carrier for the encapsulation of curcumin and then are irradiated with blue light to assess the efficacy of a combined therapy (blue light + curcumin) against drug resistant Staphylococcus aureus (S. aureus). The advantage of utilizing photodynamic therapy (PDT) is the usage of a non-antibiotic mode to inactivate bacterial cells. In the presence of blue light, the curcumin loaded alginate microfibers have shown good eradication activity against biofilms formed by multidrug resistant S. aureus. We achieved different diameters of curcumin loaded alginate microfibers through manipulation of flow rates. The curcumin loaded microfibers were characterized for their size, morphology, and curcumin encapsulation. Further, the efficacy of these microfibers in the presence of blue light has been evaluated against biofilm forming S. aureus (NCIM 5718) through optical and electron microscopy. This study employs microfluidic techniques to obtain an efficacious and cost-effective microfibrous scaffold for controlled release of curcumin to treat biofilms in the presence of blue light.

Two new cycloartane type triterpenes from Dysoxyllum binectariferum.

Dysoxyllum binectariferum is an important medicinal plant known for various biological activities like anti-inflammatory, CNS depressants, contraceptive, analgesic, immunomodulatory, antimalarial, antifeedant, leishmanicidal and antiviral. It is a rich source of rohitukine, a basic skeleton of flavopiridol. Phytochemical investigation of chloroform extracts of Dysoxyllum binectariferum leaves, lead to the isolation of beddomeilactone (1) and two new cycloartane type triterpenoids beddomeilactol (2) and binectarilactone-A (3) with modified A ring. Compounds were assessed for their in-vitro α-glucosidase inhibitory activity. Compound 1 was found to be most potent, showing IC50 of 17.99 ± 0.26 µg/ml which is comparable to the positive control acarbose.

Von Willebrand factor: A key glycoprotein involved in thrombo-inflammatory complications of COVID-19.

COVID-19 is an ongoing public health emergency that has affected millions of people worldwide and is still a threat to many more. One of the pathophysiological features of COVID-19 is associated with the activation of vascular endothelial cells (ECs) leading to the disruption of vascular integrity, coagulation and inflammation. An interlink mechanism between coagulation and inflammatory pathways has been reported in COVID-19. Multiple components are involved in these pathological pathways. Out of all, Von Willebrand Factor (VWF) is one of the primary components of coagulation pathway and also a mediator of vascular inflammation that plays an important role in thrombo-inflammation that further leads to acute respiratory distress syndrome (ARDS). The thrombo-inflammatory co-morbidities such as hyper-coagulation, thrombosis, ARDS etc. have become the major cause of mortality in the patients of COVID-19 admitted to the ICU. Thus, VWF can be explored as a potential target to manage COVID-19 associated co-morbidities. Supporting this hypothesis, there are literature reports which disclose previous attempts to target VWF for the management of thrombo-inflammation in other pathological conditions. The current report summarizes emerging insights into the pathophysiology, mechanism(s), diagnosis, management and foundations for research on this less explored clinically relevant glycoprotein as coagulation biomarker in COVID-19.

Microfluidics-based generation of cell encapsulated microbeads in the presence of electric fields and spatio-temporal viability studies.

Microfluidics based techniques for generation of cell-laden microbeads are emerging as an attractive route to 3D cell encapsulation due to the precise control provided by microfluidics. However, existing microfluidics based cell encapsulation methods are restricted to 2D planar devices and use of passive methods for droplet generation. In this work, we report the development of a 3D glass-PDMS (polydimethylsiloxane) hybrid device for complete on-chip generation of cell-laden alginate beads in the presence of electric fields. The 3D hybrid device allows application of electric fields for active control of droplet (sodium alginate) size without the need for electrode patterning or liquid electrodes. Chemical gelation is achieved through on-chip coalescence of sodium alginate droplets and calcium chloride plugs, generated using coflow and T-junction geometries respectively. Using this approach, we successfully encapsulate E. coli cells (with viability ∼90 %) into alginate microbeads and perform comprehensive spatio-temporal growth and viability studies. The active control of droplet size coupled with complete on-chip gelation demonstrated here is a promising technology for cell encapsulation with applications such as cell therapy, organ repair, biocatalysis, and microbial fuel cells.

The interplay between inflammatory pathways and COVID-19: A critical review on pathogenesis and therapeutic options.

COVID-19, caused by SARS-CoV-2, emerged as the deadliest outbreak that has now become a serious health issue to mankind. Activation of inflammatory signaling pathways and cytokine storm are crucial factors that lead to acute respiratory distress syndrome (ARDS) in COVID-19 patients. Excessive secretion of pro-inflammatory cytokines and chemokines leads to the dysregulation of the innate immune system. The cytokine storm attracts many inflammatory cells that infiltrate into the lung tissues and ultimately cause immune damage. In addition to the dysregulation of the immune system, dysfunction of the renin-angiotensin system (RAS) due to the downregulation of ACE2 is also associated with the mortality of COVID-19 patients. Both the mechanisms are directly or indirectly associated with cytokine storm that promotes vascular hyperpermeability, vascular edema leading to hypercoagulation and hence multiorgan damage. As of now, there is no specific treatment available for COVID-19, but scientists have purposed several treatment options including cytokine inhibitors, JAK inhibitors, immunomodulators, plasma therapy, etc. In this article, we have provided the detailed mechanism of occurrence of SARS-CoV-2 induced inflammatory storm and its connection with the pre-existing inflammatory conditions. Possible treatment options to cope up with the severe clinical manifestations of COVID-19 are also discussed.

Bloodstain age estimation through infrared spectroscopy and Chemometric models.

The chemical profiling of bloodstains is essential to link the suspect with the crime. The current study proposed a proof-of-concept methodology for the investigation of bloodstains by utilizing advanced ATR-FTIR spectroscopy coupled with new generation chemometric methods. Current study providesencouraging datato allow discrimination between human and animal blood though with small sample size. In this study, different models for the age estimation of human bloodstains are developed from the trained data sets of 1-175 days old bloodstains. The models such as curve estimation (CE), multiple linear regression (MLR), and partial least squares regressions (PLSR) are developed to determine the best prediction model for aged human bloodstains. The obtained results on the dating of bloodstains are very encouraging and also tested for unknown samples. The maximum dating errors are observed in the curve estimation models whereas, the other models MLR, PLSR show excellent age estimation of unknown bloodstains. These models represent an error of ~3 ± 1 days and ~4 ± 1 days in actual and estimated date, respectively, which is lowest ever reported so far. The present methodology is expected to provide a valuable insight into forensic society and hence, to the law enforcement community. The present methodology can further be explored for an ideal model by including all other external variables/factors and for more longer aging time.

Preparation, characterization and in vitro cytotoxicity of Fenofibrate and Nabumetone loaded solid lipid nanoparticles.

There is an increasing attention on solid lipid nanoparticles (SLNs) due to their high biocompatibility and ability to enhance bioavailability for poorly water-soluble drugs. Preparation of SLNs that are capable of high drug loading and sustained drug release through hot melt sonication method is reported here. SLNs of palmitic acid and stearic acid loaded with poorly water-soluble drugs, viz. fenofibrate (FF) and nabumetone (NBT) having spherical morphology and average particle size below 200 nm were prepared. Poloxamer 407 and pluronic® F-127 were used as surfactants. Particle size and spherical morphology was confirmed by dynamic light scattering, field emission scanning electron microscopy, transmission electron microscopy, and atomic force microscopy. The chemical, crystal, and thermal properties of SLNs were studied by Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry, respectively. The palmitic acid-poloxamer 407 SLNs could entrap upto 13.8% FF with 80% entrapment efficiency while the stearic acid-pluronic® F-127 SLNs entrapped 13.6% NBT with 89% entrapment efficiency. The drug loaded in SLNs showed controlled release up to 3 days as confirmed by in-vitro drug release profile. Moreover, the drug loaded SLNs did not show any toxicity on macrophage cell line proving the use of these formulations as control drug delivery vehicles for the studied drugs.

Expression of vitamin D hydroxylases and bone quality in obese mice consuming saturated or monounsaturated enriched high-fat diets.

Obesity induced by high-fat diets (HFDs) is inversely associated with vitamin D status and bone health. However, the associations and effects of excessive fat intake on hepatic and renal vitamin D metabolism have not been addressed. The primary objective was to determine if excessive energy and fat intake, or the type of fat, affects serum 25-hydroxycholecalciferol concentration and whether this can be explained by an alteration of vitamin D-regulating enzymes in older mice. The second objective was a follow up of our recent findings that a high intake of monounsaturated fatty acids (MUFA) is not detrimental to bone in lean mice and whether this is also true under conditions of diet-induced obesity. In the study, twenty-one 8-month-old female C57BL/6 J mice were fed ad libitum for 10 weeks with a 10% normal-fat diet (NFD) or 45% HFD enriched with MUFA or saturated fatty acids (SFA). We found that the HFD, compared with NFD, resulted in greater energy intake, weight gain, total body fat, and liver fat (P < .05). Only the high SFA feeding resulted in higher mRNA but lower protein abundance of hepatic Cyp2r1 and lower renal Cyp24a1 mRNA expression than the NFD group (P < .05). Moreover, although bone mineral density did not differ among groups, the percent difference compared with NFD was significantly lower for SFA (P < .05) but not MUFA. Also, femoral trabecular bone volume fraction was lower (P < .05) only in the SFA compared with the NFD group. In conclusion, high SFA and MUFA feeding differentially affected gene and protein expressions of major vitamin D hydroxylases compared with NFD, but this was unrelated to the lower circulating 25-hydroxycholecalciferol concentration. In addition, only the SFA diet alters vitamin D metabolism and bone changes, indicating the importance of dietary fat composition.

Antimicrobial photodynamic therapy: Single-walled carbon nanotube (SWCNT)-Porphyrin conjugate for visible light mediated inactivation of Staphylococcus aureus.

Due to the excessive use of antibiotics over the years, the microorganisms have developed resistance to numerous drugs. The growth of multi-resistant organisms (MROs) heads due to the insufficient treatment with the currently available medications which present a great threat to the biotic component of the environment as well as to the food technology sectors. The goal of this research was to develop a nano-composite made up of single-walled carbon nanotubes (SWCNTs) and amine-functionalized porphyrin, which could further be used for the anti-microbial studies in presence of visible light showing photodynamic effect to inactivate cells. Photodynamic antimicrobial chemotherapy is gaining significant interest due to its capabilities as an innovative form of antimicrobial treatment. The development of anti-microbial photodynamic therapy (a-PDT) is a non-antibiotic access to inactivate microorganisms. We examined the synthesis of amine-functionalized porphyrin and conjugated it to the oxidised single-walled carbon nanotubes (SWCNTs). By the use of appropriate amount of single-walled carbon nanotubes (SWCNTs), we have shown the interaction between the porphyrin conjugated nanotubes and the bacterial cells in presence of visible light led to the cell membrane damage, concluding that SWCNT-porphyrin conjugates can be used as an antibacterial agent. The characterization of the oxidised SWCNT and SWCNT-porphyrin conjugates was determined by field emission scanning electron microscopy (FE-SEM), which provides detailed information about the composition and the morphological analysis. The particle size measurements were carried out by transmission electron microscopy (TEM). On investigating under the florescence microscopy, red fluorescence was observed. Thus, these properties demand us to design this facile material comprised of SWCNT-aminoporphyrin conjugates that shows potent antibacterial activity.