Assessment of thermal damage for plasmonic photothermal therapy of subsurface tumors.

Plasmonic photothermal therapy (PPTT) involves the use of nanoparticles and near-infrared radiation to attain a temperature above 50 °C within the tumor for its thermal damage. PPTT is largely explored for superficial tumors, and its potential to treat deeper subsurface tumors is dealt feebly, requiring the assessment of thermal damage for such tumors. In this paper, the extent of thermal damage is numerically analyzed for PPTT of invasive ductal carcinoma (IDC) situated at 3-9 mm depths. The developed numerical model is validated with suitable tissue-tumor mimicking phantoms. Tumor (IDC) embedded with gold nanorods (GNRs) is subjected to broadband near-infrared radiation. The effect of various GNRs concentrations and their spatial distributions [viz. uniform distribution, intravenous delivery (peripheral distribution) and intratumoral delivery (localized distribution)] are investigated for thermal damage for subsurface tumors situated at various depths. Results show that lower GNRs concentrations lead to more uniform internal heat generation, eventually resulting in uniform temperature rise. Also, the peripheral distribution of nanoparticles provides a more uniform spatial temperature rise within the tumor. Overall, it is concluded that PPTT has potential to induce thermal damage for subsurface tumors, at depths of upto 9 mm, by proper choice of nanoparticle distribution, dose/concentration and irradiation parameters based on the tumor location. Moreover, intravenous administration of nanoparticles seems a good choice for shallower tumors, while for deeper tumors, uniform distribution is required to attain the necessary thermal damage. In the future, the algorithm may be extended further, involving 3D patient-specific tumors and through mice model-based experiments.

Role of periodic irradiation and incident beam radius for plasmonic photothermal therapy of subsurface tumors.

Plasmonic photothermal therapy (PPTT) is a potential technique to treat tumors selectively. However, during PPTT, issue of high temperature region and damage to the surrounding healthy is still need to be resolved. Also, treatment of deeper tumors non-invasively is a challenge for PPTT. In this paper, the effect of periodic irradiation and incident beam radius (relative to tumor size) for various gold nanorods (GNRs) concentrations is investigated to avoid much higher temperatures region with limiting thermal damage to the surrounding healthy tissue during PPTT of subsurface breast tumors located at various depths. Lattice Boltzmann method is used to solve Pennes' bioheat model to compute the resulting photothermal temperatures for the subsurface tumor embedded with GNRs subjected to broadband near infrared radiation of intensity 1 W/cm2. Computation revealed that low GNRs concentration leads to uniform internal heat generation than higher GNRs concentrations. The results show that deeper tumors, due to attenuation of incident radiation, show low temperature rise than shallower tumors. For shallower tumors situated 3 mm deep, 70% irradiation period resulted in around 20 °C reduction (110 °C-90 °C) of maximum temperature than that with the continuous irradiation. Moreover, 70% beam radius (i.e., beam radius as 70% of the tumor radius) causes less thermal damage to the nearby healthy tissue than 100% beam radius (i.e., beam radius equal to the tumor radius). The thermal damage within the healthy tissue is minimized to the 1 mm in radial direction and 3 mm in axial direction for 70% beam radius with 70% irradiation period. Overall, periodic heating and changing beam radius of the incident irradiation lead to reduce high temperature and limit healthy tissue damage. Hence, discussed results are useful for selection of the irradiation parameters for PPTT of sub-surface tumors.

A systematic overview of metal nanoparticles as alternative disinfectants for emerging SARS-CoV-2 variants.

Coronaviruses are a diverse family of viruses, and new strains can emerge. While the majority of coronavirus strains cause mild respiratory illnesses, a few are responsible for severe diseases such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). SARS-CoV-2, the virus responsible for COVID-19, is an example of a coronavirus that has led to a pandemic. Coronaviruses can mutate over time, potentially leading to the emergence of new variants. Some of these variants may have increased transmissibility or resistance to existing vaccines and treatments. The emergence of the COVID-19 pandemic in the recent past has sparked innovation in curbing virus spread, with sanitizers and disinfectants taking center stage. These essential tools hinder pathogen dissemination, especially for unvaccinated or rapidly mutating viruses. The World Health Organization supports the use of alcohol-based sanitizers and disinfectants globally against pandemics. However, there are ongoing concerns about their widespread usage and their potential impact on human health, animal well-being, and ecological equilibrium. In this ever-changing scenario, metal nanoparticles hold promise in combating a range of pathogens, including SARS-CoV-2, as well as other viruses such as norovirus, influenza, and HIV-1. This review explores their potential as non-alcoholic champions against SARS-CoV-2 and other pandemics of tomorrow. This extends beyond metal nanoparticles and advocates a balanced examination of pandemic control tools, exploring their strengths and weaknesses. The manuscript thus involves the evaluation of metal nanoparticle-based alternative approaches as hand sanitizers and disinfectants, providing a comprehensive perspective on this critical issue.

Limits of antibacterial activity of triangular silver nanoplates and photothermal enhancement thereof for Bacillus subtilis.

Currently, nanoparticles are being actively explored for antimicrobial applications involving variety of pathogens. Bacillus subtilis is a major concern considering its sporulation and biofilm formation capability which involves high bacteria loadings. Also, there is natural ability of B subtilis to adapt and develop resistance to the silver nanoparticles alone. So, this study reports the limits of antibacterial activity of triangular silver nanoplates (∆AgNPs) and further photothermal enhancement for B. subtilis ATCC 6051 for considerably high bacterial load of 2.5 × 107 to 5 × 108 CFU/ml. Triangular silver nanoplates were synthesized using one pot synthesis method and showed significant photothermal response i.e., ∼36 °C temperature rise on near infrared irradiation as well as photothermal stability. Triangular silver nanoplates alone showed absolute destruction for 2.5 × 107 CFU/ml initial B. subtilis load in 5 min. Whereas, for further higher bacterial loads, the antibacterial efficacy of ∆AgNPs is observed to be insignificant. For higher initial bacterial loads of 5 × 107 CFU/ml and 5 × 108 CFU/ml, photothermally enhanced triangular silver nanoplates resulted in complete destruction of bacteria in about 5 and 10 min, respectively. Antibacterial efficacy and mechanism of the destruction assessed via scanning electron microscopy and LIVE/DEAD assay confirmed morphological deformities. Further the generation of higher levels of reactive oxygen species is also confirmed due to photothermal activation of ∆AgNPs. The study concludes that ∆AgNPs alone are effective only up to bacterial load of 2.5 × 107 CFU/ml. Whereas, for higher bacterial loads of B. subtilis, photothermally activated ∆AgNPs lead to irreversible damage due to multiple targeting mechanisms leading to absolute elimination in short span of 5-10 min for the chosen irradiation conditions. Ultimately, this study demonstrates photothermally enhanced silver nanoplates as a potential antimicrobial agent for considerably high bacterial loads of B. subtilis. Overall, the broader window of considered high bacterial loadings and its irradiation by this technique shows the full-proof nature of photothermal applications for scenarios involving high cell density such as biofilms and wound infections etc. Further, the concept may be useful for sterilization or decontamination of samples, devices, etc. because B. subtilis and its spores are the challenges during sterilization.

Biosynthesis of silver nanoparticles using nitrate reductase from Aspergillus terreus N4 and their potential use as a non-alcoholic disinfectant.

Green technology has been developed for the quick production of stabilized silver nanoparticles (AgNPs), with the assistance of nitrate reductase from an isolated culture of Aspergillus terreus N4. The organism's intracellular and periplasmic fractions contained nitrate reductase, with the former demonstrating the highest activity of 0.20 IU/g of mycelium. When the fungus was cultivated in a medium comprising 1.056% glucose, 1.836% peptone, 0.3386% yeast extract, and 0.025% KNO3, the greatest nitrate reductase productivity of 0.3268 IU/g was achieved. Statistical modeling via response surface methodology was used to optimize the enzyme production. The periplasmic and intracellular enzyme fractions were found to convert Ag+ to Ag0, initiating synthesis within 20 min, with predominant nanoparticle sizes between 25 and 30 nm. By normalizing the effects of temperature, pH, AgNO3 concentration, and mycelium age with a variable shaking period for enzyme release, the production of AgNPs with the periplasmic fraction was optimized. The synthesis of nanoparticles occurred at temperatures of 30, 40, and 50 °C, with the highest yield observed at 40 and 50 °C during shorter incubation periods. Similarly, the nanoparticles were synthesized at pH levels of 7.0, 8.0, and 9.0, with the greatest production observed at pH 8.0 and 9.0 at lower incubation periods. The antimicrobial activity of AgNPs was demonstrated against common foodborne pathogens, including Staphylococcus aureus and Salmonella typhimurium, indicating their potential as non-alcoholic disinfectants.

Gold nanoblackbodies-based multifunctional nanocomposite for multimodal cancer therapy.

Multifunctional nanocomposites are of potential use to achieve complete tumor elimination and, thus, to avoid tumor recurrence. Herein, polydopamine (PDA)-based gold nanoblackbodies (AuNBs) loaded with indocyanine green (ICG) and Doxorubicin (DOX) termed as A-P-I-D nanocomposite were investigated for multimodal plasmonic photothermal-photodynamic-chemotherapy. Upon near-infrared (NIR) irradiation, A-P-I-D nanocomposite showed enhanced photothermal conversion efficiency of 69.2% compared to bare AuNBs (62.9%) due to the presence of ICG, along with ROS (1O2) generation as well as enhanced DOX release. On assessment of therapeutic effects on breast cancer (MCF-7) and melanoma (B16F10) cell lines, A-P-I-D nanocomposite showed significantly lower cell viabilities of 45.5% and 24% compared to 79.3% and 76.8% for AuNBs. Fluorescence images of stained cells revealed characteristic signs of apoptotic mode of cell death, with almost complete damage on A-P-I-D nanocomposite + NIR treated cells. Further, on evaluation of photothermal performance through breast tumor-tissue mimicking phantoms, A-P-I-D nanocomposite provided required thermal ablation temperatures within the tumor along with the potential for the elimination of residual cancerous cells through photodynamic therapy and chemotherapy. Overall, this study demonstrates that A-P-I-D nanocomposite + NIR provides better therapeutic outcome on cell lines and enhanced photothermal performance on breast tumor-tissue mimicking phantoms to be a promising agent for multimodal cancer therapy.

Preparation, characterization, and safety assessment of statistical optimized probiotic supplemented herbal wine from Tinospora cordifolia.

Evidently proven medicinal benefits of Tinospora cordifolia and the growing demand of functional foods have created scientific interest in the functional beverage. Therefore, an attempt was made to prepare probiotic Lactiplantibacillus pentosus GSSK2 supplemented herbal wine having the benefits of both phytochemical and probiotic. Experimentally, fermentation of Tinospora cordifolia stem was found to be the most effective with ammonium dihydrogen phosphate, potassium phosphate, magnesium sulfate, isoleucine, and thiamine that yielded maximum ethanol (6.8 to 10%), total phenol (419 to 791.5 µg/ml), and antioxidants capacity (98.2 to 160.4 µmol/ml) after optimizing physical parameters, i.e., 20° Brix total soluble solid, pH 4.5, temperature 30 °C, and 10% (v/v) inoculum. Further, prepared herbal wine was supplemented separately with seven different probiotic strains and among these Lactiplantibacillus pentosus GSSK2 had the highest 88.6% survival rate compared with other probiotics and was safe showing 100% survivability of HEK-293 and THP-1 cells. Both herbal- and probiotic-supplemented herbal wine showed the antimicrobial potential against Gram-positive and Gram-negative bacteria as probiotic-supplemented herbal wine had 19-21 mm inhibition zone compared with 18-19 mm with herbal wine. LC-MS analysis of the probiotic-supplemented herbal wine revealed the presence of various phytochemicals such as alkaloids, diterpenoid lactone, glycoside, steroids having anti-bacterial, anti-oxidant, and anti-inflammatory potential. This is the first ever such study to demonstrate the antibacterial, antioxidant potential and safety of probiotic supplemented herbal wine in vitro.

Concentration-dependent photothermal conversion efficiency of gold nanoparticles under near-infrared laser and broadband irradiation.

The photothermal conversion efficiency of gold different nanoparticles (GNPs) in different concentrations (1.25-20 µg/mL) and at different irradiation intensities of near-infrared (NIR) broadband and NIR laser irradiation is evaluated. Results show that for a concentration of 20.0 µg/mL, 40 nm gold nanospheres, 25 × 47 nm gold nanorods (GNRs), and 10 × 41 nm GNRs show a 4-110% higher photothermal conversion efficiency under NIR broadband irradiation than under NIR laser irradiation. Broadband irradiation seems suitable to attain higher efficiencies for the nanoparticles whose absorption wavelength is different from the irradiation wavelength. Lower concentrations (1.25-5 µg/mL) of such nanoparticles show 2-3 times higher efficiency under NIR broadband irradiation. For GNRs of sizes 10 × 38 nm and 10 × 41 nm, the different concentrations show almost equal efficiencies for NIR laser and broadband irradiation. On increasing the irradiation power from 0.3 to 0.5 W, for 10 × 41 nm GNRs in the concentration range of 2.5-20.0 µg/mL, NIR laser irradiation results in 5-32% higher efficiencies, while NIR broadband irradiation leads to a 6-11% increase in efficiency. Under NIR laser irradiation, the photothermal conversion efficiency increases with an increase in optical power. The findings will facilitate the selection of nanoparticle concentrations, irradiation source, and irradiation power for a variety of plasmonic photothermal applications.

Dynamic change in optical properties of a nanoparticle embedded tumor phantom for plasmonic photothermal cancer therapeutics.

In this study, the temporal dynamic changes in optical properties of gold nanorods (GNR) embedded tumor phantom, during photothermal interaction, are reported for plasmonic photothermal therapeutics. Tumor mimicking bilayer phantoms were prepared by using 1% agarose incorporated with 0.1% coffee powder, 0.3% intralipid solution as epidermis layer; 3% intralipid solution and 0.3% human hemoglobin (Hb) powder as dermis layer. On incorporating GNRs of concentrations 10, 20, and 40 µg/ml within the phantom, the absorption coefficients increases 4-8 times, while there is minimal change in the reduced scattering coefficients. Further the absorption coefficient increased by ~8% with the incorporation of GNRs of concentration 40 µg/ml, while no considerable dynamic change in the optical properties is observed for the phantom embedded with GNRs of concentrations 10, and 20 µg/ml. The discussed results are useful for the selection of GNRs dose for pre-treatment planning of plasmonic photothermal cancer therapeutics.

Gold nanoblackbodies mediated plasmonic photothermal cancer therapy for melanoma.

Aim: Gold nanoblackbodies (AuNBs)-mediated plasmonic photothermal cancer therapy was investigated through melanoma-bearing mice. Materials & methods: Polydopamine-coated Au nanoclusters were synthesized, termed AuNBs and PEGylated AuNBs (AuNBs-PEG). The photothermal response of AuNBs-PEG was evaluated upon low-intensity broadband near-infrared irradiation (785/62 nm; 0.9 Wcm-2), and cytotoxicity was assessed on B16-F10 cells. Further, the therapeutic potential of intravenously administered AuNBs-PEG was evaluated on B16-F10 melanoma in C57BL/6 mice. Results: AuNBs-PEG showed an excellent photothermal response (photothermal conversion efficiency of 60.3%), robust photothermal stability and no cytotoxicity. For AuNB-mediated plasmonic photothermal therapy, an average temperature of 63°C was attained within 5 min of irradiation, and tumors were eradicated. Conclusion: AuNBs-PEG are promising photothermal agents for treating melanoma through low-intensity broadband near-infrared irradiation.

Discovery of MDV6058 (PF-06952229), a selective and potent TGFßR1 inhibitor: Design, synthesis and optimization.

Compound 1 is a potent TGF-ß receptor type-1 (TGFßR1 or ALK5) inhibitor but is metabolically unstable. A solvent-exposed part of this molecule was used to analogue and modulate cell activity, liver microsome stability and mouse pharmacokinetics. The evolution of SAR that led to the selection of 2 (MDV6058 / PF-06952229) as a preclinical lead compound is described.

Microbially-derived cocktail of carbohydrases as an anti-biofouling agents: a 'green approach'.

Enzymes, also known as biocatalysts, display vital properties like high substrate specificity, an eco-friendly nature, low energy inputs, and cost-effectiveness. Among their numerous known applications, enzymes that can target biofilms or their components are increasingly being investigated for their anti-biofouling action, particularly in healthcare, food manufacturing units and environmental applications. Enzymes can target biofilms at different levels like during the attachment of microorganisms, formation of exopolymeric substances (EPS), and their disruption thereafter. In this regard, a consortium of carbohydrases that can target heterogeneous polysaccharides present in the EPS matrix may provide an effective alternative to conventional chemical anti-biofouling methods. Further, for complete annihilation of biofilms, enzymes can be used alone or in conjunction with other antimicrobial agents. Enzymes hold the promise to replace the conventional methods with greener, more economical, and more efficient alternatives. The present article explores the potential and future perspectives of using carbohydrases as effective anti-biofilm agents.

Photo-thermally enhanced antimicrobial efficacy of silver nanoplates against Gram-negative, Gram-positive bacterial and fungal pathogens.

AIM: This paper aims to investigate the photo-thermally enhanced antimicrobial efficacy of triangular silver nanoplates for a broad range of harmful pathogens viz., Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Staphylococcus aureus), and fungus (Candida albicans). METHODS AND RESULTS: Triangular silver nanoplates were synthesized using the chemical method and were characterized for optical absorption, size and morphology, surface charge and concentration via UV-Vis spectroscopy, transmission electron microscopy, zeta potential analysis and inductively coupled plasma mass spectrometry, respectively. Furthermore, the photo-thermally enhanced antimicrobial efficacy of the triangular silver nanoplates (10 µg/ml concentration) was evaluated on broadband near-infrared irradiation. The photothermal response shows that for the fixed concentration of silver nanoplates, the smaller-sized nanoplates (~52 nm) lead to higher temperature rise than larger-sized nanoplates (~68 nm). It is demonstrated that within a short exposure duration of 15 min, the photothermal activation of silver nanoplates led to ~5 log10 CFU/ml reduction for E. coli and C. albicans, and ~7 log10 CFU/ml reduction for S. aureus from a considerably high initial load of 5 × 108  CFU/ml. CONCLUSIONS: The present study demonstrates that photo-thermally enhanced triangular silver nanoplates possess much stronger antimicrobial efficacy over a short exposure duration of few minutes and exhibits the applicability for a broad range of pathogens. SIGNIFICANCE AND IMPACT OF STUDY: The study is highly significant and explains the eradication of broad-spectrum of microbial pathogens by photo-thermally enhanced silver nanoplates in short exposure duration with low nanoparticle concentration, which is useful for diverse antibacterial and antifungal applications.

Polydopamine Coated Gold Nano Blackbodies for Tumor-Selective Spatial Thermal Damage During Plasmonic Photothermal Cancer Therapy.

Plasmonic photothermal therapy (PPTT), which involves nanoparticles and near-infrared radiation (NIR) to generate confined heat, is a potential technique for selective thermal damage of cancerous tissue. Herein, tumor-selective spatial damage characteristics during polydopamine (PDA) coated gold nano blackbodies (AuNBs) mediated PPTT is investigated through a tumor-tissue mimicking phantom. The spatial temperatures during PPTT were measured within the phantom mimicking the optical scattering of superficial invasive ductal carcinoma (injected with AuNBs) surrounded by a region without AuNBs. The phantom was irradiated using broadband NIR radiation (754-816 nm), and spatial temperatures were measured using thermocouples and an infrared thermal camera. The obtained results demonstrate that the tumor region's temperature was elevated to >50°C in about 2.5 minutes and was maintained thereafter for about 6 minutes, which is well sufficient for the thermal ablation of the tumor. While for the region surrounding the tumor, a temperature of about 40-44°C was attained, which is within safe limits for the said exposure duration. Overall, this study demonstrates that for the considered experimental parameters and tumor dimensions, heat-based thermal damage could be confined to the nanoparticle embedded tumor region while maintaining the safe temperature levels for the surrounding region, i.e., 2 mm beyond the tumor boundary.

Cocktail of carbohydrases from Aspergillus niger: an economical and eco-friendly option for biofilm clearance from biopolymer surfaces.

Biofilm formation on both biotic and abiotic surfaces accounts for a major factor in spread of antimicrobial resistance. Due to their ubiquitous nature, biofilms are of great concern for environment as well as human health. In the present study, an integrated process for the co-production of a cocktail of carbohydrases from a natural variant of Aspergillus niger was designed. The enzyme cocktail was found to have a noteworthy potential to eradicate/disperse the biofilms of selected pathogens. For application of enzymes as an antibiofilm agent, the enzyme productivities were enhanced by statistical modelling using response surface methodology (RSM). The antibiofilm potential of the enzyme cocktail was studied in terms of (i) in vitro cell dispersal assay (ii) release of reducing sugars from the biofilm polysaccharides (iii) the effect of enzyme treatment on biofilm cells and architecture by confocal laser scanning microscopy (CLSM). Potential of the enzyme cocktail to disrupt/disperse the biofilm of selected pathogens from biopolymer surfaces was also assessed by field emission scanning electron microscopy (FESEM) analysis. Further, their usage in conjunction with antibiotics was assessed and it was inferred from the results that the use of enzyme cocktail augmented the efficacy of the antibiotics. The study thus provides promising insights into the prospect of using multiple carbohydrases for management of heterogeneous biofilms formed in natural and clinical settings.

Sirtuins and the circadian clock interplay in cardioprotection: focus on sirtuin 1.

Chronic disruption of circadian rhythms which include intricate molecular transcription-translation feedback loops of evolutionarily conserved clock genes has serious health consequences and negatively affects cardiovascular physiology. Sirtuins (SIRTs) are nuclear, cytoplasmic and mitochondrial histone deacetylases that influence the circadian clock with clock-controlled oscillatory protein, NAMPT, and its metabolite NAD+. Sirtuins are linked to the multi-organ protective role of melatonin, particularly in acute kidney injury and in cardiovascular diseases, where melatonin, via upregulation of SIRT1 expression, inhibits the apoptotic pathway. This review focuses on SIRT1, an NAD+-dependent class III histone deacetylase which counterbalances the intrinsic histone acetyltransferase activity of one of the clock genes, CLOCK. SIRT1 is involved in the development of cardiomyocytes, regulation of voltage-gated cardiac sodium ion channels via deacetylation, prevention of atherosclerotic plaque formation in the cardiovascular system, protection against oxidative damage and anti-thrombotic actions. Overall, SIRT1 has a see-saw effect on cardioprotection, with low levels being cardioprotective and higher levels leading to cardiac hypertrophy.

Pre-operative Assessment of Ablation Margins for Variable Blood Perfusion Metrics in a Magnetic Resonance Imaging Based Complex Breast Tumour Anatomy: Simulation Paradigms in Thermal Therapies.

BACKGROUND AND OBJECTIVES: Image-guided medical interventions facilitates precise visualization at treatment site. The conformal prediction for sparing healthy tissue fringes precisely in the vicinity of irregular tumour anatomy remains clinically challenging. Pre-clinical image-based computational modelling is imperative as it helps in enhancement of treatment quality, augmenting clinical-decision making, while planning, targeting, controlling, monitoring and assessing treatment response with an effective risk assessment before the onset of treatment in clinical settings. In this study, the influence of heat deposition rate (SAR), exposure duration, and variable blood perfusion metrics for a patient-specific breast tumour is quantified considering the tumour margins thereby suggesting need of geometrically accurate models. METHODS: A three-dimensional realistic model mimicking dimensions of a female breast, comprising ~1.7 cm irregular tumour, was generated from patient specific two-dimensional DICOM format MRI images through image segmentation tools MIMICS 19.0® and 3-Matic 11.0® which is finally exported to COMSOL Multiphysics 5.2® as a volumetric mesh for finite element analysis. The Pennes bioheat transfer model and Arrhenius thermal damage model of cell-death are integrated to simulate a coupled biophysics problem. A comparative blood perfusion analysis is done to evaluate the response of tumour during heating considering thermal damage extent, including the tumour margins while sparing critical adjoining healthy tissues. RESULTS: The evaluated thermal damage zones for 1 mm, 2 mm and 3 mm fringe heating region (beyond tumour boundary) reveals 0.09%, 0.21% and 0.34% thermal damage to the healthy tissue (which is <1%) and thus successful necrosis of the tumour. The iterative computational experiments suggests treatment margins < 5 mm are sufficient enough as heating beyond 3 mm fringe layer leads to higher damage surrounding the tumour approximately 1.5 times the tumour volume. Further, the heat-dosage requirements are 22% more for highly perfused tumour as compared to moderately perfused tumour with an approximate double time to ablate the whole tumour volume. CONCLUSIONS: Depending on the blood perfusion characteristics of a tumour, it is a trade-off between heat-dosage (SAR) and exposure/treatment duration to get desired thermal damage including the irregular tumour boundaries while taking into account, the margin of healthy tissue. The suggested patient-specific integrated multiphysics-model based on MRI-Images may be implemented for pre-treatment planning based on the tumour blood perfusion to evaluate the thermal ablation zone dimensions clinically and thereby avoiding the damage of off-target tissues. Thus, risks involving underestimation or overestimation of thermal coagulation zones may be minimised while preserving the surrounding normal breast parenchyma.

Wheel-running activity rhythms and masking responses in the diurnal palm squirrel, Funambulus pennantii.

Several studies have reported activity patterns of various diurnal species from the order Rodentia, in which most of the species are nocturnal. Most of these studies have been performed under controlled laboratory conditions. These studies found that most of these species change their activity patterns when held under laboratory conditions, have a diverse masking response to light, and their activity pattern is influenced by the presence of a running wheel. Squirrels are reported to be strictly diurnal both in the field as well as in laboratory settings, and, therefore, form an interesting species to study to better understand the switch to diurnality. The aim of the current study is to characterize the masking response and temporal organization of wheel-running activity rhythms in the palm squirrel, Funambulus pennantii, under semi-natural (NLD) and controlled laboratory conditions using different lighting schedules. Squirrels were housed individually in a resting cage with running wheel under NLD (n = 10) and squared 12:12 h of light-dark cycle (LD) (n = 20). After stable entrainment under the LD condition, squirrels were divided into two groups. One group was housed under constant darkness (DD) (n = 10) and another group under constant light (LL) (n = 10). Following the stable free-running rhythm under DD and LL, the LD condition was reinforced. The kinetics of the endogenous pacemaker was studied following a 6 h phase advance or delay of LD cycle. Further, palm squirrels were subjected to a 3.5: 3.5 h LD cycle to evaluate the masking response to light and dark. Squirrels demonstrated stable, clear, robust, and strict diurnal activity rhythm during NLD and LD. In DD and LL, F. pennantii free-ran from the phase of the previous LD cycle, and the free-running period was longer in LL than in DD. The percentage of activity during the light phase was significantly higher in NLD and LD (above 96%) compared to activity during the subjective day in the DD and LL conditions (above 91%). The alpha/rho ratio was significantly higher in the LL compared to other lighting schedules. Further, all ten squirrels re-entrained to both 6 h advance and delay shifts within 11 days. In the ultradian cycle, significant positive masking of light was evident in nine of ten squirrels. These results suggest that the: (i) circadian system of F. pennantii is stable and functional under various lighting conditions; (ii) basic temporal organization in activity pattern remained unaltered even in the presence of a running wheel; (iii) diurnality is the inherent trait of F. pennantii, and (iv) behavioral activity rhythms are governed by both the circadian clock and external masking. Thus, palm squirrels can be used as a suitable diurnal model in circadian biology to study the underlying mechanisms of diurnality and effects of different light schedules, wavelengths, and non-photic cues on physiological and behavioral parameters.

Near-infrared stimulated hydrogel patch for photothermal therapeutics and thermoresponsive drug delivery.

Nanotechnology driven cancer theranostics hold potential as promising future clinical modalities. Currently, there is a strong emphasis on the development of combinational modalities, especially for cancer treatment. In this study, we present a topical hydrogel patch for nanomaterial-assisted photothermal therapeutics as well as for on-demand drug delivery application. The patch was derived from interpenetrating networks (IPNs) of alginate (Alg) and polyacrylamide (PAAm) in weight ratio 8:1 by free radical polymerization. The patch interiors were composed of hybrid nanostructures derived from gold nanorods (AuNRs) anchored onto polyvinylpyrrolidone (PVP) functionalized graphene oxide (PVP-nGO) to form PVP-nGO@AuNRs hybrids. Field emission scanning electron microscopy (FE-SEM) images revealed the porous nature of the hybrid hydrogel patch with an average pore size of ~28.60 ± 3.10 µm. Besides, functional characteristics of the hybrid patch, such as mechanical strength, viscoelastic and swelling behavior, were investigated. Under near-infrared (NIR) radiation exposure, the hybrid patch exhibited photothermal properties such as surface temperature rise to 75.16 ± 0.32 °C, sufficient to ablate cancer cells thermally. Besides, the heat generated in the hybrid patch could be transmitted to an underlying hydrogel (mimicking skin tissue) when stacked together without much loss. Under cyclic photothermal heating, the patch could retain its photothermal stability for four cycles. Furthermore, the hybrid patch demonstrated NIR stimulated drug release, which was evaluated using methotrexate (MTX, water-insoluble anticancer drug) and rhodamine B (RhB, water-soluble dye). Taken together, this work provides a new dimension towards the development of externally placed hydrogel patches for thermal destruction of localized solid tumors and tunable delivery of chemotherapeutic drugs at the target site.

Melatonin-induced phase and dose responses in a diurnal mammal, Funambulus pennantii.

Melatonin, an essential pineal hormone, acts as a marker of the circadian clock that regulates biological rhythms in animals. The effects of exogenous melatonin on the circadian system of nocturnal rodents have been extensively studied; however, there is a paucity of studies on the phase-resetting characteristics of melatonin in diurnal rodents. We studied the phase shifting effects of exogenous melatonin as a single melatonin injection (1 mg/kg) at various phases of the circadian cycle on the circadian locomotor activity rhythm in the palm squirrel, Funambulus pennantii. A phase response curve (PRC) was constructed. Adult male squirrels (N = 10) were entrained to a 12:12 h light-dark cycle (LD) in a climate-controlled chronocubicle with food and water provided ad libitum. After stable entrainment, squirrels were transferred to constant dark condition (DD) for free-running. Following stable free run, animals were administered a single dose of melatonin (1 mg/kg in 2% ethanol-phosphate buffered saline (PBS) solution) or vehicle (2% ethanol-PBS solution) at circadian times (CTs) 3 h apart to evoke phase shifts. The phase shifts elicited at various CTs were plotted to generate the PRC. A dose response curve was generated using four doses (0.5, 1, 2 and 4 mg/kg) administered at the CT of maximum phase advance. Melatonin evoked maximum phase advances at CT0 (1.23 ± 0.28 h) and maximum phase delays at CT15 (0.31 ± 0.09 h). In the dose response experiment, maximal phase shifts were evoked with 1 mg/kg. In contrast, no significant shifts were observed in control groups. Our study demonstrates that the precise timing and appropriate dose of melatonin administration is essential to maximize the amelioration of circadian rhythm-related disorders in a diurnal model.