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OBJECTIVE: The ocular vascular system plays an important role in preserving the visual function. Alterations in either anatomy or hemodynamics of the eye may have adverse effects on vision. Thus, an imaging approach that can monitor alterations of ocular blood flow of the deep eye vasculature ranging from capillary-level vessels to large supporting vessels would be advantageous for detection of early stage retinal and optic nerve diseases. METHODS: We propose a super-resolution ultrasound localization microscopy (ULM) technique that can assess both the microvessel and flow velocity of the deep eye with high resolution. Ultrafast plane wave imaging was acquired using an L22–14v linear array on a high frequency Verasonics Vantage system. A robust microbubble localization and tracking technique was applied to reconstruct ULM images. The experiment was first performed on pre-designed flow phantoms in vitro and then tested on a New Zealand white rabbit eye in vivo calibrated to various intraocular pressures (IOP) – 10 mmHg, 30 mmHg and 50 mmHg. RESULTS: We demonstrated that retinal/choroidal vessels, central retinal artery, posterior ciliary artery, and vortex vein were all visible at high resolution. In addition, reduction of vascular density and flow velocity were observed with elevated IOPs. CONCLUSION: These results indicate that super-resolution ULM is able to image the deep ocular tissue while maintaining high resolution that is comparable with optical coherence tomography angiography. SIGNIFICANCE: Capability to detect subtle changes of blood flow may be clinically important in detecting and monitoring eye diseases such as glaucoma.

The aim of the present study was focused on experimental analysis for medicinal use of Micromeria biflora Benth. The plant was collected and subjected to extraction and fractionation; the chloroform fraction resulted in the isolation of a new constituent salicylalazine, using preparative HPLC. The Chemical structure of salicylalazine was confirmed through NMR and high-resolution mass spectrometry. Salicylalazine was evaluated (in vitro) against various biological targets such as urease, phosphodiesterase-1, tyrosinase, and anti-glycation studies. Furthermore, the binding orientation and interaction pattern of salicylalazine with crucial amino acid residues of the respective targets were used to explore the mechanism of enzymes inhibition. Results indicated that salicylalazine caused potent urease inhibition with an IC50 value of 12.4 ± 1.10 µM, in comparison of standard thiourea (IC50 = 21.0 ± 0.21 µM). The compound exhibited excellent inhibition potential against tyrosinase (89.4%), phosphodiesterase-1 (94.7%) compared to the standards kojic acid (86.3%) and EDTA (86.4%), respectively. Besides, salicylalazine possessed good anti-glycation activity with % inhibition of 86% and IC50 value of 248.7 ± 2.09 µM, compared to the standard Rutin (96%, IC50 value of 295 ± 3.14). Thus, it is concluded that salicylalazine, the active constituent Micromeria biflora Benth, exhibited remarkable in vitro inhibition of urease, phosphodiesterase-1, tyrosinase, and anti-glycation.

The control and inhibition of microbial infection are of critical importance for patients undergoing dental or orthopedic surgery. A critical requirement is the prevention of bacterial growth, subsequent bacterial colonization of implant surfaces, and biofilm formation. Among biofilm-forming bacteria, S. aureus and S. epidermidis are the most common bacteria responsible for causing implant-related infections. The ability to produce customized and patient-specific antimicrobial treatments will significantly reduce infections leading to enhanced patient recovery. We propose that 3D-printed antimicrobial biomedical devices for on-demand infection prophylaxis and disease prevention are a rational solution for the prevention of infection. In this study, we modified 3D printed polylactic acid (PLA) constructs using an alkali treatment to increase hydrophilicity and functionalized the surface of the constructs using a suspension of Zinc/HNTs-Ag-Chitosan Oligosaccharide Lactate (ZnHNTs-Ag-COS). The morphologies of printed constructs were analyzed using Scanning Electron Microscopy-Energy Dispersive X-Ray Spectroscopy (SEM-EDS), and chemical analysis by Fourier-transform infrared spectroscopy (FTIR). Assessment of the antimicrobial potential of our constructs was assessed using agar diffusion and biofilm assays. The surface of 3D printed PLA constructs were chemically modified to increase hydrophilicity and suspensions of COS-ZnHNTs-Ag were adsorbed on the construct surface. Surface adsorption of ZnHNTs-Ag-COS on PLA printed constructs was determined to be a function of relative pore size. Morphological surface characterization using SEM-EDS confirmed the presence of the suspension coatings on the constructs, and FTIR analysis confirmed the presence of COS-ZnHNTs-Ag in the coatings. The inhibition of bacterial growth was evaluated using the agar diffusion method. Results obtained confirmed the antimicrobial potential of the PLA constructs (which was a function of the Ag content in the material).

Lower mantle “garbage can” Calcium silicate perovskite has finally been identified in a natural sample and now has the mineral name davemaoite. Tschauner et al . discovered the type mineral trapped at high pressure and temperature as a diamond inclusion (see the Perspective by Fei). Structural and chemical analysis of the mineral showed that it is able to host a wide variety of elements, not unlike fitting bulky objects into garbage can. Specifically, it has a large amount of trapped potassium. Davemaoite can thus host three of the major heat-producing elements (uranium and thorium were previously shown experimentally) affecting heat generation in Earth’s lower mantle. —BG

To understand the expected mode of action, the physicochemical study on the solution properties of medicinal compounds and their interaction with deoxyribonucleic acid (DNA), under varying experimental conditions, is of prime importance. The present research work illustrates the physicochemical study and interaction of certain medicinal compounds such as; Levofloxacin, Ciprofloxacin, and Ibuprofen with DNA. Density, viscosity and surface tension measurements have been performed in order to determine, in a systematic manner, the physicochemical, volumetric and thermodynamic properties of these compounds; and most of these parameters have shown different behavior with varying concentration of solution, temperature of the medium and chemical nature/structure of the compound. In addition, these drugs showed a spontaneous surface-active and association behavior in aqueous solutions. The flow behavior, surface properties, volumetric behavior and solute–solvent interaction of these drugs were prominently influenced by experimental variables and addition of DNA to their solutions. UV–Visible spectroscopy was also used to examine the interaction of these drugs with DNA in aqueous media in detail. Calculated values of binding constants (Kb) for all complexes of drug-DNA are positive, indicating a fruitful binding process. It is seen that a smaller Kb value reflects weaker binding of the drug with DNA and vise versa. Due to the difference in the chemical structure of drugs the values of binding constant are different for various drug-DNA complexes and follow the order Kb(Levofloxacin-DNA) > Kb(Ciprofloxacin-DNA) > Kb(Ibuprofen-DNA). On the basis of spectral changes and Kb it can be said that the binding of all these drugs with DNA may be of physicochemical nature and the dominating binding force be of hydrogen bonding between oxygen of drugs and hydrogen of DNA units and the drug having more oxygen atoms showed stronger binding ability. The data further suggest a limited possibility of chemical type attachment of these drugs with DNA.

The destructive aphid (Sitobion avenae) of wheat, generally accomplished by chemical pesticides, is responsible for the substantial agricultural damages that occur annually. The present experimental study, a protein elicitor, PeBL1, has been examined for the possibility of inducing a defense response to S. avenae in wheat. In comparison to the positive (Water) and negative 70.58 μg ml−1 (50 mM Tris–HCl, pH 8.0) controls, the population growth (intrinsic Increase) rates of S. avenae (second and third generation) with PeBL1-treated wheat seedlings declined. S. avenae preferred control plants for colonizing in an experiment with the host selection compared with the PeBL1-treated wheat plants, with PeBL1 treated wheat seedlings; the nymphal development time of aphid has been extended. In comparison with positive (water) and negative controls, less fecundity was observed with less offspring's in PeBL1-treated wheat seedlings. S. avenae had a harmful surface environment for wheat seedlings treated with PeBL1, caused by trichomes and wax formation. The level of Jasmonic acid (JA), salicylic acid (SA) and ethylene (ET) was significantly higher, and the PeBL1 treated wheat seedlings had significant accumulations. The findings presented that PeBL1 considerably altered the wheat surface structure so that the replication of S. avenae was minimized and colonization was prevented. Defensive processes also include pathway activation (JA, SA, and ET). A biocontrol study for the use of PeBL1 in the protection against S. avenae has been produced in this area.

This study was conducted to evaluate the comparative efficacy of hyperosmotic sodium bicarbonate (HSB 8.4%), hypertonic saline (HSS 7.5%) and normal saline (NSS 0.9%) solutions associated with experimentally Salmonella-induced diarrhoea in buffalo neonatal calves. For this purpose, 14–17 days old 18 healthy buffalo calves were reared. After 8–12 h of oral administration of Salmonella broth (6.5 × 108 CFU), diarrhoea was induced successfully. Calves were then randomly divided into three equal groups viz., groups A, B and C and treatment was instituted. Group A received NSS (0.9%) @ 60 mL/kg (body weight) B.W, intravenous (IV) once, group B was administered HSS (7.5%) @ 5 mL/kg B.W, IV once and group C instituted with HSB (8.4%) @ 5 mL/kg B.W, IV once. All three groups were additionally treated with ciprofloxacin @ 7 mg/kg B.W, IV bid and flunixin meglumine @ 2 mg/kg B.W, IV tid. Comparative efficacy of all treatment regimens was assessed through haemodynamic measurements, blood gases determination and serum electrolyte analysis. All parameters were noted at baseline (prior to diarrhoea induction), during neonatal diarrhoea, t=3, t=9, t=18, t=36, t=72, t=120, t=168 h after treatment. The HSB treated calves (group C) revived from diarrhoea quickly (within 9 h) and efficiently than NSS (group A) and HSS (group B), exhibited significantly (P < 0.05) enhancement. At t=18 h, values for central venous partial pressure and systemic vascular resistance were 11.67 ± 0.7, 13.67 ± 0.61 and 13.50 ± 0.56 and 1180. 83 ± 6.94, 1180.83 ± 6.94 and 1465.00 ± 6.76 in groups A, B and C, respectively. HSB treated buffalo neonatal calves also showed significant increase in bicarbonate, blood pH, serum electrolytes and partial pressure of venous oxygen. Basis on the results of this study, it was concluded that small-volume administration of HSB profoundly ameliorated deleterious effects of septicaemia and improve haemodynamic stability in Salmonella-induced bubaline neonatal diarrhoea. It provides a practical and economical method to resuscitate dehydrated diarrhoeic calves thus make it convenient to accomplish in on-farm situation. © 2021 Friends Science Publishers

The development of new tools that could meet the demand of sustainable energy production has attracted worldwide scientific attention. Over the past few decades, significant research efforts have been carried out to efficiently reduce water to H2 (green fuel) over semiconductor photocatalysts. Numerous semiconductor photocatalysts have been employed in photocatalysis for optimum H2 production. All the techniques were chosen based on their flexibility, cost-effectiveness, and ease of availability. Recently, polymeric carbon nitride (g-C3N4) received worldwide attention in visible light photocatalysis for energy and environmental applications due to its low price, robust nature, and superior thermal stability. Nevertheless, g-C3N4 (CN) exhibits shortfalls such as high charge carrier's recombination rate and weak reduction ability. To overcome these drawbacks, herein, for the first time we have fabricated B-TiO2/MIL-53(Fe)/CN ternary composite via hydrothermal and wet-chemical methods. The resultant B-TiO2/MIL53(Fe)/CN ternary composite shows drastically improved photocatalytic activity for hydrogen evolution compared to the bare CN, B-TiO2, and MIL53(Fe) components. The B-TiO2/MIL53(Fe)/CN ternary composite produced approximately 166.3 and 581.2 μmol h−1 g−1 of hydrogen under visible light and UV–visible light irradiations, respectively, with the assistance of co-catalyst Pt. Photo-luminescence (PL) and the fluorescence (FL) spectroscopy measurements reveal that the enhanced photoactivity is due to the greatly promoted charge carrier's separation and transfer at the interfacial contact of the well-aligned three-component systems. This work will promote the design and development of efficient photocatalyst based on CN for clean energy production and environmental purification.

The green peach aphid (Myzus persicae Sulzer), a major and harmful chili aphid usually managed using chemical pesticides, is responsible for massive annual agricultural losses. The efficacy of two protein elicitors, PeaT1 and PeBC1, to stimulate a defensive response against M. persicae in chili was studied in this study. When compared to positive (water) and negative (buffer, 50 mM Tris-HCl, pH 8.0) controls, the rates of population growth (intrinsic rate of increase) of M. persicae (second and third generations) were lower with PeaT1- and PeBC1-treated chilli seedlings. M. persicae demonstrated a preference for colonizing control (12.18 ± 0.06) plants over PeaT1- (7.60 ± 0.11) and PeBC1 (6.82 ± 0.09) treated chilli seedlings in a host selection assay. Moreover, PeaT1- and PeBC1-treated chilli seedlings, the nymphal development period of the M. persicae was extended. Similarly, fecundity was lowered in the PeaT1- and PeBC1-treated chilli seedlings, with fewer offspring produced compared to the positive (water) and negative controls (50 mM Tris-HCl, pH 8.0). The trichomes and wax production on the PeaT1 and PeBC1-treated chilli leaves created a disadvantageous surface environment for M. persicae. Compared to control (30.17 ± 0.16 mm−2), PeaT1 (56.23 ± 0.42 mm−2) and PeBC1 (52.14 ± 0.34 mm−2) had more trichomes. The levels of jasmonic acid (JA), salicylic acid (SA), and ethylene (ET) were significantly higher in the PeaT1- and PeBC1-treated chili seedlings, indicating considerable accumulation. PeaT1 and PeBC1 significantly affected the height of the chili plant and the surface structure of the leaves, reducing M. persicae reproduction and preventing colonization, according to the data. The activation of pathways was also part of the defensive response (JA, SA, and ET). This present research findings established an evidence of biocontrol for the utilization of PeaT1 and PeBC1 in the defence of chili plants against M. persicae.

Decontamination of pathogens on surfaces of substances is very important for controlling infectious diseases. In the present experiments, we tested various disinfectants in aqueous phase as well as on plastic surface carrying a viral inoculum, through dropping and wiping decontamination techniques, comparatively, so as to evaluate virucidal efficacies of those disinfectants toward an avian coronavirus (infectious bronchitis virus: IBV). We regard this evaluation system applicable to SARS-CoV-2. The disinfectants evaluated were 0.17% food additive glade calcium hydroxide (FdCa(OH)2) solution, sodium hypochlorite at 500 or 1,000 ppm of total chlorine (NaClO-500 or NaClO-1,000, respectively), NaClO at 500 ppm of total chlorine in 0.17% FdCa(OH)2 (Mix-500) and quaternary ammonium compound (QAC) diluted 500-fold in water (QAC-500). In the suspension test, all solutions inactivated IBV inoculum that contained 5% fetal bovine serum (FBS) under detectable level within 30 sec. In the carrier test, all solutions, except NaClO-500, could inactivate IBV with 0.5% FBS on a carrier to undetectable level in the wiping-sheets and wiped-carriers. We thus conclude that suspension and carrier tests should be introduced to evaluate disinfectants for the field usage, and that this evaluation system is important and workable for resultful selection of the tested disinfectants against avian coronavirus and SARS-CoV-2 on surfaces, particularly on plastic fomite.

The microbicidal activities of mixtures of quaternary ammonium compounds (QACs) and food additive grade calcium hydroxide (FdCa(OH)2) were evaluated in a suspension test at -20°C using an anti-freeze agent (AFA) containing methanol, or at 1°C, with varying contact time, toward avian influenza virus (AIV), Newcastle disease virus (NDV), fowl adenovirus (FAdV), avian reovirus (ARV), Salmonella Infantis (SI) and Escherichia coli (EC). At -20°C, the mixtures could inactivate AIV and NDV within 30 min, FAdV and ARV within 5 sec, and SIand EC within 3 min, respectively. AFA did not inactivate viruses and bacteria within 30 minutes and 10 minutes, respectively. At 1°C, the mixtures inactivated FAdV and ARV within 30 sec, AIV within 10 min, and NDV within 30 min. A mixture of slaked lime (SL) and QAC could inactivate FAdV and ARV within 30 sec, but could not inactivate AIV and NDV even after 60 min at 1°C. SL could not substitute FdCa(OH)2 in order to exert the synergistic effects with QAC. Thus, QACs microbicidal activities were maintained or enhanced by adding FdCa(OH)2. It is hence recommended to use QACs with FdCa(OH)2, especially in the winter season.

Purpose: To report the anatomical and functional outcomes of Argus II retinal prosthesis implantation in Korean patients. Methods: We included 5 consecutive patients with end-stage retinitis pigmentosa (RP) who underwent Argus II retinal prosthesis implantation and were followed for at least 12 months. The transcorneal electrical evoked response was utilized for patient selection. We used intraoperative optical coherence tomography (OCT) for optimal placement of the array and provided specialized vision rehabilitation training. A morphological evaluation using SD-OCT and a functional evaluation using computer-based visual function tests, a letter-reading ability test, and the Functional Low-Vision Observer Rated Assessment (FLORA) were conducted. Results: Postoperatively, the array was completely apposed to the retinal surface in all eyes, except for one eye which had a preexisting macular concavity. Fibrosis-like tissues of ≥50-μm thickness developed at the interface in 2 eyes. All of the patients showed improvement in computer-based visual function tests and could read ETDRS letters at a distance of 50 cm. Three patients could read Korean words. FLORA was improved in all patients, mainly in tasks of visual mobility, daily activities, and social interactions. Conclusions: Along with good anatomical outcomes and specialized rehabilitation practices, recipients of the Argus II implant showed profound improvements in functional vision and mobility.

Retinal prostheses aim at restoring partial sight to patients that are blind due to retinal degenerative diseases by electrically stimulating the surviving healthy retinal neurons. Ideally, the electrical stimulation of the retina is intended to induce localized, focused, percepts only; however, some epiretinal implant subjects have reported seeing elongated phosphenes in a single electrode stimulation due to the axonal activation of retinal ganglion cells (RGCs). This issue can be addressed by properly devising stimulation waveforms so that the possibility of inducing axonal activation of RGCs is minimized. While strategies to devise electrical stimulation waveforms to achieve a focal RGCs response have been reported in literature, the underlying mechanisms are not well understood. This article intends to address this gap; we developed morphologically and biophysically realistic computational models of two classified RGCs: D1-bistratified and A2-monostratified. Computational results suggest that the sodium channel band (SOCB) is less sensitive to modulations in stimulation parameters than the distal axon (DA), and DA stimulus threshold is less sensitive to physiological differences among RGCs. Therefore, over a range of RGCs distal axon diameters, short-pulse symmetric biphasic waveforms can enhance the stimulation threshold difference between the SOCB and the DA. Appropriately designed waveforms can avoid axonal activation of RGCs, implying a consequential reduction of undesired strikes in the visual field.

Porous ZnO/cellulose nanofiber (CNF) composites were synthesized to investigate their photocatalytic degradation of methylene blue (MB) dye (a persistent organic pollutant model) under a UV lamp an...

The aim of this work was to examine the ameliorative effect of foliar application of salicylic acid and potassium on antioxidant enzymes activity in wheat under saline conditions. Two wheat genotypes WL-711 (salt tolerant) and Kohistan-97 (salt sensitive) were used with salicylic acid (SA) and potassium (K+) foliar spray which were applied at both vegetative and grain filling stage under saline conditions. Various enzymatic antioxidant activities include catalase (CAT), peroxidase (POD), superoxide dismutase (SOD) and ascorbate peroxidase (APX) was assesed. Result cleared that foliar spray of salicylic acid and potassium decreased the damaged effect of salinity in both wheat genotypes especially Kohistan-97 which was more salt sensitive. Overall, foliarly applied salicylic acid and potassium reduces the adverse effects of reactive oxygen species and antioxidant enzymes on cellular metabolism that was disturbed by salt stress.

BackgroundType 1 diabetes (T1D) has been increasing globally over the past three decades. Self-monitoring of blood glucose is a challenge in both developed as well as developing countries. Self-management guidelines include maintaining logbooks for blood glucose, physical activity, and dietary intake that affect glycated hemoglobin (HbA1c) and a multitude of life-threatening acute complications. Innovative, cost-effective interventions along with beneficial lifestyle modifications can improve home-based self-monitoring of blood glucose in T1D patients. The overall objective of this study is to evaluate the relationship between maintaining log books for blood glucose levels, reinforcement by e-messages, and/or daily step count and changes in HbA1c.Methods/designA randomized controlled trial will enroll participants aged 15 years and above in four groups. Each group of 30 participants will be working with a newly designed standard log book for documenting their blood glucose. The first group will be entirely on routine clinical care, the second group will be on routine care and will receive an additional e-device for recording step count (fit bit), the third group will receive routine care and daily motivational e-messages to maintain the log book, and the fourth group along with routine care will receive an e-device for measuring step count (fit bit) and e-messages about maintaining the log book. Patients will be enrolled from pediatric and endocrine clinics of a tertiary care hospital in Karachi. All groups will be followed up for a period of 6 months to evaluate outcomes. Log book data will be obtained every 3 months electronically or during a patient’s clinic visit. HbA1c as a main outcome will be measured at baseline and will be evaluated twice every 3 months. A baseline questionnaire will determine the socio-demographic, nutritional, and physical activity profile of patients. Clinical information for T1D and other co-morbidities for age of onset, duration, complications, hospitalizations, habits for managing T1D, and other lifestyle characteristics will be ascertained. Behavioral modifications for maintaining daily log books as a routine, following e-messages alone, fit bit alone, or e-messages plus using fit bit will be assessed for changes in HbA1c using a generalized estimated equation.DiscussionThe proposed interventions will help identify whether maintaining log books for blood glucose, motivational e-messages, and/or daily step count will reduce HbA1c levels.Trial registrationClinicalTrials.gov,NCT03864991. March 6, 2019.

The seasonal and tidal variations of physicochemical parameters, nutrient concentrations and chlorophyll a concentration from the water of Passur river and Koromjol canal in the Sundarbans mangrove ecosystems were investigated during March 2018 to February 2019. Samples were collected from five sampling stations during March, August and November where these months were considered as pre-monsoon, monsoon and post-monsoon seasons, respectively. The nutrients NH3-N, NO3-N, PO4-P, SO4 and Chlorophyll a concentrations were found 0.001 to 0.09, 3.5 to 50, 0.06 to 5.4, 30 to 272 and 0.18 to 1.75 mg/L, respectively, during high tides, and 0.001 to 0.39, 4.2 to 47, 0.1 to 2.75, 20 to 179 and 0.218 to 1.88 mg/L, respectively, during low tides. The NO3-N was very high than suitable limit during both tides at monsoon and post-monsoon season. The PO4-P was found moderately high during both tides at all stations. The SO4 was found to be 187.8 and 76.87 mg/L during high tide, and 135.4 and 95.73 mg/L during low tides in pre-monsoon and post-monsoon, respectively, that were very high than water quality standards. The Passur river and the Koromjol canal were fluctuating seasonally and tidally in some magnitude and their variations can alter the water quality as well as the density and distribution of living organisms.

190 children aged 7-18 years from an endemic fluorotic village “Talab Sarai (n = 130) and a non-fluorotic, control, village “Ottawa” (n = 60) were selected for comparison. Children were examined for fluoride (F-) concentration in drinking water, urine, and serum as well as Dental fluorosis (DF) and thyroid hormone levels. The mean concentration of water fluoride (WF) in the sample group was 6.23 mg/L, urine fluoride (UF) 3.38 mg/L, and serum fluoride (SF) 0.21 mg/L, while DF was 93.07%. Significant elevations (P = 0.000) in the concentration of all these four variables were observed in sample group children as compared to control. Mean Free Tetra-iodothyronine (FT4), Free Tri-iodothyronine (FT3) and Thyroid Stimulating Hormone (TSH) concentrations in the sample group were 16.64pmol/L, 5.57 pmol /L and 4.41 mlU/L, respectively. No marked difference in FT4 (P = 0.1) was noted, while significant elevations in FT3 and TSH (P = 0.000) were found in the sample relative to the control group. 80% of the children displayed clear thyroid hormonal derangements, with 36.92% having high TSH and 43.07% with FT3 and FT4 disorders. A moderate to strong correlation among WF, UF, SF and DF (r = 0.94, 0.60, 0.60, 0.72) and a very strong correlation between WF and TSH (r = 0.9) were observed. Our results suggest that excess F- level that is four times greater than the “safe limit” is not only increasing fluoride concentration in body fluids but is also affecting thyroid hormones in 4 out of 5 children which could lead to abnormal physical and mental growth in later developmental stages.

Refereed/Peer-reviewed Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder in which the body's defense system wrongly attacks healthy body tissues. The objective of this current setup was to quantify and compare the serum concentration of ascorbic acid (Vit-C), malondialdehyde (MDA), c-reactive protein (CRP) and trace elements (Cu, Fe, Mn and Zn) in SLE and normal subjects. Methods: The proposed case-control study was performed with 25 SLE patients and 25 healthy subjects as case and control, respectively. The serum level of malondialdehyde (MDA) and vitamin C was evaluated by UV spectrophotometric method. For the determination of CRP, the latex agglutination method was used, whereas serum trace elements were estimated by atomic absorption spectroscopy (AAS). Results: This analysis demonstrated that patients with SLE possessed a significant (p < 0.001) higher level of MDA and lower level of vitamin C compared to control subjects. Pearson's correlation analysis found negative correlation between the serum level of MDA and vitamin C (r= -0.023, p = 0.887) for patients while control group also possessed similar result (r= -0.157, p = 0.453). The current findings have also revealed that serum level of Zn and Cu in SLE patients was significantly (p < 0.05) lowered to that of the control group, while serum level of Mn also showed a similar scenario. During Pearson's correlation analysis a significantly (p < 0.05) negative correlation was found between Zn and Mn (r= -0.410, p = 0.042) in patients' group. Conclusion: Although our study was limited to a small sample size and confined to a particular area of the country, the study results support a significant role of antioxidants, CRP, and trace elements in the generation of SLE and, therefore, recommends a large spectrum study of the associations between SLE and these biochemical parameters. usc

In this research work five types of titanium dioxide (TiO2) nanocrystalline sol–gel paste with three different types of dye have been prepared and layered on Indium Tin-Oxide coated glass to fabricate dye-sensitized solar cells. The dyes extracted from Malabar spinach seeds (MSS), Red spinach and Pomegranate burgs were used as photosensitizer. All the electrical properties investigated by LCR meter were found to be improved with MSS dye but sample with 0.3 M HNO3 (sample-3) exhibited the best electrical properties. The current–voltage characteristics for all the samples showed ideal behavior. The highest maximum power of 176.3 μW and efficiency of 9.23% was found for sample-3 with MSS dye. The smallest crystallite size was found to be 28.82 nm for sample-3 by XRD data which was also supported by the SEM results. Thus, this study reveals that MSS dye has the great potential to be used as photosensitizer.

RAF family kinases are RAS-activated switches that initiate signalling through the MAP kinase cascade to control cellular proliferation, differentiation and survival1–3. RAF activity is tightly regulated and inappropriate activation is a frequent cause of cancer4–6; however, the structural basis for RAF regulation is poorly understood at present. Here we use cryo-electron microscopy to determine autoinhibited and active-state structures of full-length BRAF in complexes with MEK1 and a 14-3-3 dimer. The reconstruction reveals an inactive BRAF–MEK1 complex restrained in a cradle formed by the 14-3-3 dimer, which binds the phosphorylated S365 and S729 sites that flank the BRAF kinase domain. The BRAF cysteine-rich domain occupies a central position that stabilizes this assembly, but the adjacent RAS-binding domain is poorly ordered and peripheral. The 14-3-3 cradle maintains autoinhibition by sequestering the membrane-binding cysteine-rich domain and blocking dimerization of the BRAF kinase domain. In the active state, these inhibitory interactions are released and a single 14-3-3 dimer rearranges to bridge the C-terminal pS729 binding sites of two BRAFs, which drives the formation of an active, back-to-back BRAF dimer. Our structural snapshots provide a foundation for understanding normal RAF regulation and its mutational disruption in cancer and developmental syndromes. The autoinhibited and active states of full-length BRAF in complexes with its substrate MEK1 and the 14-3-3 protein are determined by cryo-electron microscopy.

Nanostructured thin film coatings of copper oxide (Cu-oxide) were investigated to determine their physical structure, surface morphology, surface electronic bonding states, and optical properties. The Cu-oxide had been coated onto reflective aluminum substrates via a facile one-step sol–gel dip-coating route using a copper nitrate precursor. Characterizations were conducted using X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), field emission scanning electron microscopy (FESEM), and ultra-violet visible (UV–Vis) spectroscopic methods, and representative sol-gel reactions using copper nitrate precursor were proposed. The XPS spectra confirmed the presence of copper oxide elements. Further exploration of the Cu2p3/2 peak in XPS spectra revealed that the electronic structure of the copper component consisted of tetrahedral Cu(I) and octahedral Cu(II) with the presence of octahedral Cu(II) enabling coatings to have high absorption levels across the solar spectrum. The deconvolution of the O1s spectra exhibited three curve-fitting components: the lattice O2−, surface oxygen, and subsurface O− species. FESEM results showed that the coating surface was an agglomerated copper oxide nanoparticles structure forming a porous structure. The optical band-gap of Cu-oxide thin film coatings, via the Tauc plot, was 2.7 eV.

Sulfenamide based radical generators that contain a nitrogen-sulfur (N-S) core, can alone provide flame retardancy in polypropylene (PP), polyethylene and polystyrene, as we have earlier demonstrated. Herein, sulfenamides potential as synergists with conventional halogen free flame retardants has been explored. Thus, five different sulfenamides were individually combined with selected eco-friendly, phosphorus based flame retardants or aluminium trihydroxide (ATH), and their effect on polypropylene flammability was assessed by limiting oxygen index (LOI), vertical flammability (UL 94 V) and cone calorimeter tests. Thermogravimetric analysis (TGA) and nuclear magnetic resonance (NMR) studies were carried out to detect changes in thermal behaviour when such two component FR systems were mixed together at different ratios. TGA-FTIR (thermogravimetric analysis-Fourier transform infrared spectroscopy) was used to investigate the differences in decomposition products of non-flame retarded versus flame retarded PP. Strong synergistic effects were observed, and the UL 94 V-0 rating was reached for PP with a total FR loading of 10 wt% using 8 wt% of phosphonate ester AFLAMMIT® PCO 900 together with 2 wt% of sulfenamide flame retardant. In a ternary mixture of an additional phosphazene additive (SPB-100), the needed total concentration for V-0 rating was further reduced to 9 wt%. In addition, the combination of 4 wt% of aluminum hypophosphite (AHP) with 0.5 wt% of sulfenamide offered a unique halogen free solution for achieving UL 94 V-2 rating in PP. Cone calorimeter studies of an ammonium polyphosphate-pentaerythritol based intumescent system in combination with 0.5 wt% of sulfenamide also showed encouraging results. The char stability was enhanced, the peak of heat release rate (HRR), CO and CO2 production and total smoke generation were all reduced compared to the reference sample without sulfenamide.

The NLRP3 inflammasome can be activated by stimuli that include nigericin, uric acid crystals, amyloid-β fibrils and extracellular ATP. The mitotic kinase NEK7 licenses the assembly and activation of the NLRP3 inflammasome in interphase. Here we report a cryo-electron microscopy structure of inactive human NLRP3 in complex with NEK7, at a resolution of 3.8 A. The earring-shaped NLRP3 consists of curved leucine-rich-repeat and globular NACHT domains, and the C-terminal lobe of NEK7 nestles against both NLRP3 domains. Structural recognition between NLRP3 and NEK7 is confirmed by mutagenesis both in vitro and in cells. Modelling of an active NLRP3–NEK7 conformation based on the NLRC4 inflammasome predicts an additional contact between an NLRP3-bound NEK7 and a neighbouring NLRP3. Mutations to this interface abolish the ability of NEK7 or NLRP3 to rescue NLRP3 activation in NEK7-knockout or NLRP3-knockout cells. These data suggest that NEK7 bridges adjacent NLRP3 subunits with bipartite interactions to mediate the activation of the NLRP3 inflammasome. A cryo-electron microscopy structure of human NLRP3 in complex with the mitotic kinase NEK7 provides insights into the interactions that mediate the activation of the NLRP3 inflammasome.

In the present study, molybdenum doped chromium nitride coatings deposited onto silicon substrates via unbalanced magnetron sputtering, in as-deposited and annealed conditions, at 500–800 °C in steps of 100 °C, were studied to reveal their temperature dependent structural, morphological, optical and mechanical behaviors. An analysis of these features was carried out using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), ultraviolet visible (UV–Vis) spectroscopy, nanoindentation and finite element modeling (FEM) techniques. XRD results exhibited a significant improvement in the crystallinity of the Molybdenum (Mo)-doped chromium nitride (CrN) coatings along (111) and (200) diffraction planes, as the annealing temperatures increased. The lattice parameters gradually decreased from 4.20 to 4.12 A as the temperature increased. The same tendency was also observed for lattice microstrains and residual stresses. Smooth grain-like surfaces were observed by FESEM imaging techniques. At an annealing temperature of 700 °C, the spectral absorptance of Mo:CrN films attained its peak value (86%), whereas the energy band-gaps were reduced from 2.48 to 1.14 eV. The other optical parameters such as complex dielectric constants, Urbach energy values, and steepness parameters of these coatings were also discussed. The hardness and elastic modulus of the as-deposited Mo:CrN films were estimated to be 18.4 and 287 GPa, respectively. At a film thickness of 1.0 μm, the highest stress of 20 GPa was evaluated, via FEM studies, at the interface between the film and the substrate. As the film thickness was enhanced, the stress level decreased. At higher annealing temperatures, both the mechanical hardness (H) and the elastic modulus (E) of Mo-doped CrN coatings dwindled.

Legumes play a predominant role in nitrogen cycling having the unique features of biological nitrogen fixation. An experiment was conducted to estimate yield, nitrogen use efficiency (NUE) and the proportion of nitrogen fixation in plant segments i.e. roots, shoots, leafs and seeds of lentil. Three treatments such as 0 kg/ha, 11.5 kg/ha and 25.3 kg/ha were used in this experiment. The highest dry matter yield obtained were 43.44 kg/ha, 2677 kg/ha, 1450 kg/ha and 1604 kg/ha at roots, shoots, leaves and seeds respectively with the treatment 11.5 kg/ha N level.15N labelled urea was applied to wheat and lentil at 5%15N atom excess. The total nitrogen content in lentil was found 8.39 % with an average yield of 104.5 kg N/ha whereas it was 1.95% with an average yield of 102.8 kg N/ha in case of wheat. Nitrogen derived from fertilizer in lentil was 1.173% with an average fertilizer N yield of 12.085 kg/ha whereas it was 7.538% with an average yields of 223.16 kg N/ha in wheat. Lentil fixed around 85% of its required nitrogen from atmosphere through biological fixation and a minimal amount of 14.387% of nitrogen was drawn from soil source. Nitrogen use efficiency in seed was 110.1 % in lentil and 36.22% in wheat which were much higher than the other plant segments in both cases.

End-stage age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are two major retinal degenerative (RD) conditions that result in irreversible vision loss. Permanent eye damage can also occur in battlefields or due to accidents. This suggests there is an unmet need for developing effective strategies for treating permanent retinal damages. In previous studies, co-grafted sheets of fetal retina with its retinal pigment epithelium (RPE) have demonstrated vision improvement in rat retinal disease models and in patients, but this has not yet been attempted with stem-cell derived tissue. Here we demonstrate a cellular therapy for irreversible retinal eye injuries using a “total retina patch” consisting of retinal photoreceptor progenitor sheets and healthy RPE cells on an artificial Bruch’s membrane (BM). For this, retina organoids (ROs) (cultured in suspension) and polarized RPE sheets (cultured on an ultrathin parylene substrate) were made into a co-graft using bio-adhesives [gelatin, growth factor-reduced matrigel, and medium viscosity (MVG) alginate]. In vivo transplantation experiments were conducted in immunodeficient Royal College of Surgeons (RCS) rats at advanced stages of retinal degeneration. Structural reconstruction of the severely damaged retina was observed based on histological assessments and optical coherence tomography (OCT) imaging. Visual functional assessments were conducted by optokinetic behavioral testing and superior colliculus electrophysiology. Long-term survival of the co-graft in the rat subretinal space and improvement in visual function were observed. Immunohistochemistry showed that co-grafts grew, generated new photoreceptors and developed neuronal processes that were integrated into the host retina. This novel approach can be considered as a new therapy for complete replacement of a degenerated retina.

In this study, the quantum chemical properties, nonbonding interactions, and spectroscopic insights of a wide variety of choline chloride (ChCl)-based deep eutectic solvents were investigated employing molecular dynamics (MD), density functional theory, and spectroscopic analyses. Nine experimentally reported ChCl-based deep eutectic solvents (DESs) were selected for this study where ChCl was common in all the DESs and the hydrogen bond donors (HBDs) were varied. The most energetically favorable cluster was selected using MD simulation followed by density functional theory calculation. The most stable cluster structures were fully optimized, and their quantum chemical properties and IR spectra were computed at the ωB97XD/6-31G++(d,p) level of theory. Principal component analysis was performed to distinguish their behavioral differences and to find out if any correlation exists among the 1:1 and 1:2 clusters. The atom-atom radial distribution functions based on MD simulations revealed that several hydrogen bonds were formed among the donor and acceptor molecules. However, the most prominent hydrogen bonds were found to be N-HHBD⋯Cl- for ChCl:U, ChCl:TU, and ChCl:Ace and O-HHBD⋯Cl- for ChCl:Glu, ChCl:Ma, ChCl:Ox, ChCl:Gly, and ChCl:Phe. Both N-HHBD⋯Cl- and O-HHBD⋯Cl- were major interactions for ChCl:Pro, where Cl- worked as a bridge between Ch+ and the respective donors. In addition, the -OH of Ch+ showed strong intermolecular interactions with the acceptor groups of the donor molecules, such as C=O and O-H. This study has tried to extract a pattern of the contributions of HBDs by comparing the structural, spectroscopic, and thermodynamic properties of ChCl-based DESs, which have also been successfully correlated with the intermolecular interactions.

Electrochemical CO2 reduction reaction (CO2RR) provides a promising approach to curbing harmful emissions contributing to global warming. However, several challenges hinder the commercialization of this technology, including high overpotentials, electrode instability, and low Faradic efficiencies of desirable products. Several materials have been developed to overcome these challenges. This mini-review discusses the recent performance of various cobalt (Co) electrocatalysts, including Co-single atom, Co-multi metals, Co-complexes, Co-based metal–organic frameworks (MOFs), Co-based covalent organic frameworks (COFs), Co-nitrides, and Co-oxides. These materials are reviewed with respect to their stability of facilitating CO2 conversion to valuable products, and a summary of the current literature is highlighted, along with future perspectives for the development of efficient CO2RR.

Rakkyo (Allium chinense), is a Japanese leek that is primarily used to make a popular sweet or sour pickled dish. Lactic acid bacteria are often involved in the preparation steps of fermented pickles, which helps in the effective preservation of the natural bioactive compounds of fruits and vegetable, and thereby exert several health benefits including immunomodulation and growth per-formance. This work aimed to evaluate the in vivo effects of adding Lactiplantibacillus plantarum N14 fermented rakkyo pickled juice as feed supplement on the immunocompetence and production performance of pigs. We first analyzed the nutritional composition, which revealed that the proportion of protein, lipid, and water-soluble fiber content were estimated as of 4%, 5%, and 5% in rakkyo residual liquid or juice, while 22%, 15% and 14%, respectively, were estimated in rakkyo residual powder. For the in vivo feeding trials, three groups of pigs were treated either with 5%, 20%, or 40% mixture (v/v) of fermented rakkyo pickled juice and the grinded residual liquid supplemented in the drinking water in addition to standard feed. The results of the feeding trials showed that the administration of a juice mixture of 5% or 20% (fermented pickled juice and residual liquid) had a similar trend of effects in improving the complement activity, phagocytic activity and leucocytes counts in the peripheral blood when compared to pigs fed with 40% mixture or untreated controls. Those changes were related to an improved resistance to enteric infections. Moreover, animals receiving a mixture of fermented pickled juice and fermented rakkyo residues had a higher growth rate and carcass quality than controls. The results suggested that the use of 5% mixture of fermented rakkyo pickled juice and the residual liquid through drinking water could be a cost-effective approach to promote the immune-health and production performance of pigs. This approach would contribute not only to the sustainable management of food wastes but also to the application of a value-added feed supplement for the promotion of animal health and production. Fil: Islam, Md Aminul. Tohoku University; Japón. Bangladesh Agricultural University; Bangladesh Fil: Hashiguchi, Kenji. No especifíca; Fil: Humayun Kober, A.K.M.. Tohoku University; Japón. Chittagong Veterinary and Animal Sciences University; Bangladesh Fil: Morie, Kyoko. Tohoku University; Japón Fil: Zhou, Binghui. Tohoku University; Japón Fil: Tomokiyo, Mikado. Tohoku University; Japón Fil: Shimazu, Tomoyuki. Miyagi University; Japón Fil: Aso, Hisashi. Tohoku University; Japón Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Suda, Yoshihito. Miyagi University; Japón Fil: Kitazawa, Haruki. Tohoku University; Japón

Epiretinal prostheses aim at electrically stimulating the inner most surviving retinal cells—retinal ganglion cells (RGCs)—to restore partial sight to the blind. Recent tests in patients with epiretinal implants have revealed that electrical stimulation of the retina results in the percept of color of the elicited phosphenes, which depends on the frequency of stimulation. This paper presents computational results that are predictive of this finding and further support our understanding of the mechanisms of color encoding in electrical stimulation of retina, which could prove pivotal for the design of advanced retinal prosthetics that elicit both percept and color. This provides, for the first time, a directly applicable “amplitude-frequency” stimulation strategy to “encode color” in future retinal prosthetics through a predictive computational tool to selectively target small bistratified cells, which have been shown to contribute to “blue-yellow” color opponency in the retinal circuitry. The presented results are validated with experimental data reported in the literature and correlated with findings in blind patients with a retinal prosthetic implant collected by our group.

Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke which affects the retina. Intravenous thrombolysis is emerging as a compelling therapeutic approach. However, it is not known which patients may benefit from this therapy because there are no imaging modalities that adequately distinguish viable retina from irreversibly infarcted retina. The inner retina receives arterial supply from the central retinal artery and there is robust collateralization between this circulation and the outer retinal circulation, provided by the posterior ciliary circulation. Fundus photography can show canonical changes associated with CRAO including a cherry-red spot, arteriolar boxcarring and retinal pallor. Fluorescein angiography provides 2-dimensional imaging of the retinal circulation and can distinguish a complete from a partial CRAO as well as central versus peripheral retinal non-perfusion. Transorbital ultrasonography may assay flow through the central retinal artery and is useful in the exclusion of other orbital pathology that can mimic CRAO. Optical coherence tomography provides structural information on the different layers of the retina and exploratory work has described its utility in determining the time since onset of ischemia. Two experimental techniques are discussed. 1) Retinal functional imaging permits generation of capillary perfusion maps and can assay retinal oxygenation and blood flow velocity. 2) Photoacoustic imaging combines the principles of optical excitation and ultrasonic detection and - in animal studies - has been used to determine the retinal oxygen metabolic rate. Future techniques to determine retinal viability in clinical practice will require rapid, easily used, and reproducible methods that can be deployed in the emergency setting.

Background Quantitatively investigating the biomechanics of retina with a retinal prosthetic electrode, we explored the effects of the prosthetic electrode on the retina, and further supplemented data for a potential clinical trial. Methods Biomechanical properties were assessed with a high resolution optical coherence tomography (OCT) based elastography (OCE) system. A shaker was used to initiate elastic waves and an OCT system was used to track axial displacement along with wave propagation. Rabbits received surgery to implant the retinal prosthetic electrode, and elastic wave speed was measured before and after implantation; anatomical B-mode images were also acquired. Results Spatial-temporal maps of each layer in retina with and without prosthetic electrodes were acquired. Elastic wave speed of nerve fiber to inner plexiform layer, inner nuclear to outer nuclear layer, retinal pigmented epithelium layer and choroid to sclera layer without prosthetic electrode were found to be 3.66±0.36, 5.33±0.07, 6.85±0.37, and 9.69±0.24 m/s, respectively. With prosthetic electrode, the elastic wave speed was found to be 4.09±0.26, 5.14±0.11, 6.88±0.70, and 9.99±0.73 m/s, respectively in each layer. Conclusions Our results show that the elastic wave speed in each layer of retina is slightly faster with the retinal electrode, and further demonstrate that the retinal prosthetic electrode does not affect biomechanical properties significantly. In the future, we expect OCE technology to be used by clinicians where it could become part of routine testing and evaluation of the biomechanical properties of the retina in response to long term use of prosthetic electrodes in patients.

Taxanes remain one of the most effective medical treatments for breast cancer. Clinical trials have coupled taxanes with immune checkpoint inhibitors in patients with triple-negative breast cancer (TNBC) with promising results. However, the mechanism linking taxanes to immune activation is unclear. To determine if paclitaxel could elicit an antitumoral immune response, we sampled tumor tissues from patients with TNBC receiving weekly paclitaxel (80 mg/m2) and found increased stromal tumor-infiltrating lymphocytes and micronucleation over baseline in three of six samples. At clinically relevant concentrations, paclitaxel can induce chromosome missegregation on multipolar spindles during mitosis. Consequently, post-mitotic cells are multinucleated and contain micronuclei, which often activate cyclic GMP-AMP synthase (cGAS) and may induce a type I IFN response reliant on the stimulator of IFN genes (STING) pathway. Other microtubule-targeting agents, eribulin and vinorelbine, recapitulate this cGAS/STING response and increased the expression of immune checkpoint molecule, PD-L1, in TNBC cell lines. To test the possibility that microtubule-targeting agents sensitize tumors that express cGAS to immune checkpoint inhibitors, we identified 10 patients with TNBC treated with PD-L1 or PD-1, seven of whom also received microtubule-targeting agents. Elevated baseline cGAS expression significantly correlated with treatment response in patients receiving microtubule-targeting agents in combination with immune checkpoint inhibitors. Our study identifies a mechanism by which microtubule-targeting agents can potentiate an immune response in TNBC. Further, baseline cGAS expression may predict patient treatment response to therapies combining microtubule-targeting agents and immune checkpoint inhibitors.

Thyroid cancer is the most prevalent endocrine malignancy in the United States with greater than 53,000 new cases in 2020. There is a significant gender disparity in disease incidence as well, with women developing thyroid cancer three times more often than men; however, the underlying cause of this disparity is poorly understood. Using RNA-sequencing, we profiled the immune landscape of papillary thyroid cancer (PTC) and identified a significant inverse correlation between androgen receptor (AR) levels and the immune checkpoint molecule PD-L1. The expression of PD-L1 was then measured in an androgen responsive-thyroid cancer cell line. Dihydrotestosterone (DHT) treatment resulted in significant reduction in surface PD-L1 expression in a time and dose-dependent manner. To determine if androgen-mediated PD-L1 downregulation was AR-dependent, we treated cells with flutamide, a selective AR antagonist, and prior to DHT treatment to pharmacologically inhibit AR-induced signaling. This resulted ina> 90% restoration of cell surface PD-L1 expression, suggesting a potential role for AR activity in PD-L1 regulation. Investigation into the AR binding sites showed AR activation impacts NF-kB signaling by increasing IkBα and by possibly preventing NF-kB translocation into the nucleus, reducing PD-L1 promoter activation. This study provides evidence of sex-hormone mediated regulation of immune checkpoint moleculesin vitrowith potential ramification for immunotherapies.

Since the advent of the industrial revolution, we have seen a global rise in carbon dioxide (CO2) levels. The atmospheric concentration of CO2 has increased 47% since industrial revolution. This rise in CO2 levels has led to the global environmental problem of climate change. This is something that is impacting the global population and therefore needed to be addressed. This unprecedented rise in the carbon emissions is linked with ever increasing burning of fossil fuels. The Intergovernmental Panel on Climate Change in its 5th assessment report has attributed 65% of the CO2 emissions due to fossil fuel combustion alone in 2010. Hence, it is inevitable to curtail the CO2 emissions globally to save the planet Earth from the catastrophic impacts of the global warming and climate change. To reduce the rising CO2 levels in the atmosphere, researchers have started investigating the process of carbon capture and storage (CCS) and its subsequent utilization. In this process, the excessive CO2 is captured from the atmosphere and either stored in deep geological formations or converted into useful substances and biofuels. This not only promotes resource conservation but also converts the pollution source into a valuable resource. This chapter gives a brief introduction of the different processes that are involved in each step of CCS, starting with the capture, transport, storage, transformation, and utilization of the gas.

Purpose Preclinical and clinical data indicate that radiation therapy acts as an immune modifier, having both immune-stimulatory and immunosuppressive effects on the tumor-immune microenvironment (TIME). 3.3’-diindolylmethane (DIM) sensitizes tumor cells to radiation and protects mice from lethal doses of total body irradiation. We hypothesize that protecting nontumoral cells from the adverse effects of radiation treatment (RT) may help to correct immunosuppression resulting from radiation. Methods and Materials We generated tumor graft models using immune-competent and immune-deficient mouse strains. Narrow-beamed radiation was targeted to tumor sites using shielding. Tumor regression was monitored after DIM and RT versus RT alone. The effects of DIM on the efficacy of RT were assessed using immunohistochemistry staining and gene expression profiling. Complete blood counts, clonogenic cell survival assays, and global gene expression profiling of cultured cells were performed to study DIM’s radioprotective effects on normal cells. Results DIM enhanced tumor regression after RT in immune-competent but not immune-deficient mice. Data indicated that DIM increased intratumoral immune cells after RT, contributing to enhanced immunologic responses such as adhesion and antigen processing. DIM protected normal cells from radiation-induced immediate injuries in vitro and in vivo. Transcriptomic profiling of cultured cells showed that DIM treatment mildly increased expression of some genes that are normally induced after radiation, such as genes involved in cell cycle arrest and apoptosis. Conclusions In this study, using cultured cells and preclinical breast cancer models, we show that DIM protects normal cells from radiation-induced immediate cellular injury and combination treatment of DIM and radiation potentiates antitumor immune responses and enhances the efficacy of RT.

Age-related macular degeneration (AMD) is the primary cause of blindness in adults over 60 years of age, and clinical trials are currently assessing the therapeutic potential of retinal pigmented epithelial (RPE) cell monolayers on implantable scaffolds to treat this disease. However, challenges related to the culture, long-term storage, and long-distance transport of such implants currently limit the widespread use of adherent RPE cells as therapeutics. Here we report a xeno-free protocol to cryopreserve a confluent monolayer of clinical-grade, human embryonic stem cell-derived RPE cells on a parylene scaffold (REPS) that yields viable, polarized, and functional RPE cells post-thaw. Thawed cells exhibit ≥ 95% viability, have morphology, pigmentation, and gene expression characteristic of mature RPE cells, and secrete the neuroprotective protein, pigment epithelium-derived factor (PEDF). Stability under liquid nitrogen (LN2) storage has been confirmed through one year. REPS were administered immediately post-thaw into the subretinal space of a mammalian model, the Royal College of Surgeons (RCS)/nude rat. Implanted REPS were assessed at 30, 60, and 90 days post-implantation, and thawed cells demonstrate survival as an intact monolayer on the parylene scaffold. Furthermore, immunoreactivity for the maturation marker, RPE65, significantly increased over the post-implantation period in vivo, and cells demonstrated functional attributes similar to non-cryopreserved controls. The capacity to cryopreserve adherent cellular therapeutics permits extended storage and stable transport to surgical sites, enabling broad distribution for the treatment of prevalent diseases such as AMD.

Urothelial bladder cancer is a complex disease displaying a landscape of heterogenous molecular subtypes, mutation profiles and clinical presentations. Diagnosis and surveillance rely on flexible cystoscopy which has high accuracy, albeit accompanied by a high-cost burden for healthcare providers and discomfort for patients. Advances in "omic" technologies and computational biology have provided insights into the molecular pathogenesis of bladder cancer and provided powerful tools to identify markers for disease detection, risk stratification, and predicting responses to therapy. To date, numerous attempts have been made to discover and validate diagnostic biomarkers that could be deployed as an adjunct to the cystoscopic diagnosis and long-term surveillance of bladder cancer. We report a comprehensive literature analysis using PubMed to assess the changing trends in investigating DNA, RNA, or proteins as diagnostic urinary biomarkers over a period of 5 decades: 1970-2020. A gradual shift has been observed in research away from protein biomarkers to nucleic acids including different classes of RNA, and DNA methylation and mutation markers. Until 2000, publications involving protein biomarker discovery constituted 87% of the total number of research articles with DNA comprising 6% and RNA 7%. Since 2000 the proportion of protein biomarker articles has fallen to 40%, and DNA and RNA studies increased to 32% and 28%, respectively. Clearly research focus, perhaps driven by technological innovation, has shifted from proteins to nucleic acids. We optimistically hypothesise that, following thorough validation, a clinically useful detection test for bladder cancer based on a panel of DNA or RNA markers could become reality within 5-10 years.

Currently, blindness cannot be cured and patients' living quality can be compromised severely. Ultrasonic neuromodulation is a promising technology for the development of non-invasive cortical visual prosthesis. We investigated the feasibility of transcranial focused ultrasound (tFUS) for noninvasive stimulation of the visual cortex to develop improved visual prosthesis. tFUS was used to successfully evoke neural activities in the visual cortex (VC) of both normal and retinal degenerate (RD) blind rats. Our results showed that blind rats showed more robust responses to ultrasound stimulation compared to normal rats. (p

Traumatic brain injury (TBI) is a common and prevalent condition that affects large numbers of people across a range of ages. Individuals engaging in physical activities and victims of accidents are at a higher risk for TBI. There is a lack of available treatment specifically for TBI. Given the difficulty to determine its precise location in the brain, TBI remains difficult to fully diagnose or treat. Herein, we disclose a novel strategy for directing therapeutic agents to TBI sites, without the need to determine the precise location of the TBI activity in the brain. This novel approach is based on the use of a cyanine dye nanocage carrying Gabapentin, a known TBI therapeutic agent. Upon exposure of the cyanine nanocage to near-infrared light, the local release of Gabapentin is triggered, selectively at the TBI-affected site.

More than 2.8 million annually in the United States are afflicted with some form of traumatic brain injury (TBI), where 75% of victims have a mild form of TBI (MTBI). TBI risk is higher for individuals engaging in physical activities or involved in accidents. Although MTBI may not be initially life-threatening, a large number of these victims can develop cognitive and physical dysfunctions. These late clinical sequelae have been attributed to the development of secondary injuries that can occur minutes to days after the initial impact. To minimize brain damage from TBI, it is critical to diagnose and treat patients within the first or "golden" hour after TBI. Although it would be very helpful to quickly determine the TBI locations in the brain and direct the treatment selectively to the affected sites, this remains a challenge. Herein, we disclose our novel strategy to target cyclosporine A (CsA) into TBI sites, without the need to locate the exact location of the TBI lesion. Our approach is based on TBI treatment with a cyanine dye nanocage attached to CsA, a known therapeutic agent for TBI that is associated with unacceptable toxicities. In its caged form, CsA remains inactive, while after near-IR light photoactivation, the resulting fragmentation of the cyanine nanocage leads to the selective release of CsA at the TBI sites.

Protein kinase C beta II (PKCβII) activates polymorphonuclear leukocyte (PMN) superoxide (SO) production via NADPH oxidase (NOX-2) phosphorylation to exacerbate myocardial ischemia/reperfusion (I/R) injury. In prior studies, myristoylation (myr) of PKCβII peptide inhibitor (N-myr-SLNPEWNET; myr-PKCβII-), which disrupts PKCβII translocation/phosphorylation of NOX-2, was shown to dose-dependently attenuate PMN SO release induced by phorbol 12-myristate 13-acetate (PMA), a broad-spectrum PKC agonist. However, the role of myr on the inhibitory effects of myr-PKCβII- has yet to be elucidated. We hypothesized that myr-PKCβII peptide activator (N-myr-SVEIWD; myr-PKCβII+) would augment, myr-PKCβII- would attenuate, and scrambled myr-PKCβII- (N-myr-WNPESLNTE; myr-PKCβII-scram), a control for myr, would not affect PMA-induced PMN SO release compared to unconjugated peptides and nontreated controls. Rat PMNs (5х10 6 ) were incubated for 15 min at 37 o C in the presence/absence of SO dismutase (SOD; 10 μg/mL), unconjugated PKCβII+/-, myr-PKCβII+/-, or myr-PKCβII-scram (all 20 μM). SO release was measured by the change in absorbance at 550 nm via ferricytochrome c reduction after PMA (100 nM) stimulation for 390 sec. Data were analyzed by ANOVA using Student-Newman-Keuls post hoc analysis. Myr-PKCβII- significantly attenuated SO release (0.30±0.02; n=27; p2 O 2 , significantly reduced absorbance by 94±7%, indicating that absorbance increased mainly due to PMA stimulation. Cell viability (trypan blue exclusion) was similar in all groups (94±2%). Unexpectedly, myr-PKCβII-scram significantly stimulated the highest increase in absorbance compared to all groups (p

Reactive oxygen species (ROS) induced ischemia-reperfusion (I/R) injury is a phenomenon causing paradoxical myocardial damage after cardio-angioplasty, coronary bypass and organ transplantation. Previous studies show that a cell-permeable myristic acid (myr-) conjugated PKCβII peptide inhibitor given at reperfusion prevents PKCβII translocation (N - myr-SLNPEWNET; myr-PKCβII-) and significantly attenuates ROS mediated I/R injury. We included a scrambled myr-PKCβII- (N-myr-WNPESLNTE; myr-PKCβII-scram) to examine the effects of myr separately. We hypothesize that myr-PKCβII- will improve and myr-PKCβII activator peptide (N-myr-SVEIWD; myr-PKCβII+) will exacerbate infarct size and post-reperfused cardiac function compared to myr-PKCβII-scram and untreated controls. Hearts isolated from male Sprague-Dawley rats (~300g) were perfused with Krebs’ buffer at a constant pressure of 80mmHg and subjected to 30 min of global ischemia and 50 min reperfusion. Myr-PKCβII-, myr-PKCβII+, myr-PKCβII-scram (all 20μM), or untreated control were given during the first five minutes of reperfusion. Left ventricular (LV) dP/dt max and dP/dt min (mmHg/s) were measured using a pressure transducer, and infarct size was determined using 1% triphenyltetrazolium chloride staining comparing infarcted tissue vs. total tissue weight. Data were evaluated using ANOVA with Student-Newman-Keuls post-hoc analysis. Myr-PKCβII- (n=17) significantly improved LV dP/dt max and dP/dt min to 1535±107 and 1063±83 at 50 min post-reperfusion compared to untreated control (815±107 and 722±89; n=15); myr-PKCβII-scram (513±78 and 433±66; n=12), and myr-PKCβII+ (860±118 and 694±81; n=14) (all pmax and LV dP/dt min compared to untreated control and other treated groups (p

PurposeTo evaluate the outcome of patients with COVID-19 triggered CRS treated with Therapeutic Plasma Exchange (TPE) as compared to propensity score matched (PSM)-controls not receiving TPE.Material and methodsUsing PS 1:1 matching, 90 patients were assigned 2 groups (45 receiving TPE and 45 controls). Forced matching and covariate matching was done to overcome bias between two groups.ResultsMedian age was 60 years (range 32-73 in TPE and 37-75 in non-TPE group), p= 0.325. Median duration of symptoms 7 days (range 3-22 days in TPE and 3-20 days in non-TPE), p=0.266. Disease severity in both groups was 6.6% moderate, 44.4% severe and 49% critical. Twenty-eight-day survival was significantly superior in TPE group (91.1%) as compared to PS-matched controls (61.5%), HR 0.21, 95% CI for HR 0.09-0.53, log rank 0.002. Median duration of hospitalization was significantly reduced in TPE treated group as compared to non-TPE controls 10 days and 15 days respectively (p< 0.01). CRS resolution time was also significantly reduced in TPE treated group (6 days vs. 12 days) (p< 0.001).ConclusionUse of TPE is associated with superior overall survival, early resolution of CRS and time to discharge as compared to standard therapy for COVID-19 triggered CRS.Highlights□Cytokine release syndrome (CRS) plays a pivotal role in pathophysiology and progression to severe and critical disease in patients with COVID-19.□Beyond supportive care, there are currently no proven effective treatment options (including Tocilizumab) for coronavirus disease (COVID-19)□Therapeutic plasma exchange (TPE) may dampen CRS of COVID-19 by removing circulating cytokines and toxins□TPE is the cheapest of all novel treatments available so far to treat severe to critical COVID-19□By intervening early with TPE, mortality and morbidity associated with COVID-19 triggered CRS can be reduced

The present research is a comparative study that reports an economical and accessible method to synthesize niobium (Nb) and Tantalum (Ta) selenides and tellurides with useful application in the removal of pollutants in textile, paper, and dyeing industries as well as in medical field. In this study, solid-state process was used to generate nanocomposites and various characterization techniques were employed to compare two groups of materials under investigation. Structure, morphology, elemental constitution, and functional groups of synthesized materials were analyzed with XRD, FESEM coupled with EDS, FTIR, and Raman spectroscopy, respectively. HR-TEM images displayed nanoscale particles with tetragonal and monoclinic crystal structures. The optical properties were evaluated in terms of cut-off wavelength and optical band gap using UV-visible spectroscopy. A comparative behavior of both groups of compounds was assessed with regards to their catalytic and microcidal properties. Extracted nanocomposites when used as catalysts, though isomorphs of each other, showed markedly different behavior in catalytic degradation of MB dye in the presence of NaBH4 that was employed as a reducing agent. This peculiar deviation might be attributed to slight structural differences between them. Escherichia coli and Staphylococcus aureus (G –ve and + ve bacteria, respectively) were designated as model strains for in vitro antibacterial tests of both clusters by employing disk diffusion method. Superior antibacterial efficacy was observed for telluride system (significant inhibition zones of 26-35 mm) compared with selenide system (diameter of inhibition zone ranged from 0.8 mm to 1.9 mm). In addition, molecular docking study was undertaken to ascertain the binding interaction pattern between NPs and active sites in targeted cell protein. The findings were in agreement with antimicrobial test results suggesting NbTe4 to be the best inhibitor against FabH and FabI enzymes.

Electrical stimulation of surviving retinal neurons has proven effective in restoring sight to totally blind patients affected by retinal degenerative diseases. Morphological and biophysical differences among retinal ganglion cells (RGCs) are important factors affecting their response to epiretinal electrical stimulation. Although detailed models of ON and OFF RGCs have already been investigated, here we developed morphologically and biophysically realistic computational models of two classified RGCs, D1-bistratified and A2-monostratified, and analyzed their response to alternations in stimulation frequency (up to 200 Hz). Results show that the D1-bistratified cell is more responsive to high frequency stimulation compared to the A2-monostratified cell. This differential RGCs response suggests a potential avenue for selective activation, and in turn different encoded percept of RGCs.