Understanding the atmospheric cold plasma-induced modification of finger millet (Eleusine coracana) starch and its related mechanisms.

This research was conducted to evaluate the effects of cold plasma (CP) on finger millet starch (FMS). FMS was exposed to partially ionized gas at varying voltages (170, 200, and 230 Volt) for varied time (10, 20, and 30 mins). The impact of treatment was studied using physico-chemical, and functional properties, and the mechanisms of starch modification occurring were stated. A significant reduction in the degree of polymerization was noticed based on parameters like reducing sugar, amylose content, solubility, and molecular weight. However, in certain voltage and time combinations, crosslinking was also confirmed by analysis such as XRD, FTIR, DSC, etc. The properties of starch were altered such as remarkable increase in water solubility by 6.7 times for highest voltage and longest time (230 V/30 min) was registered. NMR data suggested valuable findings- oxidation of OH group at C6 position of starch led to formation of carbonyl group followed by carboxyl group. NMR also showed a decrease in OH protons confirming crosslinking and hence all these analyses helped to conclude findings about the quality changes using CP. It was observed that the highest voltage and considerably longer exposure time of 20 and 30 min induced significant changes in the FMS.

Collective neural network behavior in a dynamically driven disordered system of superconducting loops.

Collective properties of complex systems composed of many interacting components such as neurons in our brain can be modeled by artificial networks based on disordered systems. We show that a disordered neural network of superconducting loops with Josephson junctions can exhibit computational properties like categorization and associative memory in the time evolution of its state in response to information from external excitations. Superconducting loops can trap multiples of fluxons in many discrete memory configurations defined by the local free energy minima in the configuration space of all possible states. A memory state can be updated by exciting the Josephson junctions to fire or allow the movement of fluxons through the network as the current through them surpasses their critical current thresholds. Simulations performed with a lumped element circuit model of a 4-loop network show that information written through excitations is translated into stable states of trapped flux and their time evolution. Experimental implementation on a high-Tc superconductor YBCO-based 4-loop network shows dynamically stable flux flow in each pathway characterized by the correlations between junction firing statistics. Neural network behavior is observed as energy barriers separating state categories in simulations in response to multiple excitations, and experimentally as junction responses characterizing different flux flow patterns in the network. The state categories that produce these patterns have different temporal stabilities relative to each other and the excitations. This provides strong evidence for time-dependent (short-to-long-term) memories, that are dependent on the geometrical and junction parameters of the loops, as described with a network model.

Successful treatment approaches for tumoral calcinosis in children and young people: A condition of diverse pathogenesis.

BACKGROUND: Ectopic calcification is inappropriate biomineralization of soft tissues occurring due to genetic or acquired causes of hyperphosphataemia and rarely in normophosphataemic individuals. Tumoral Calcinosis (TC) is a rare metabolic bone disorder commonly presenting in childhood and adolescence with periarticular extra-capsular calcinosis. Three subtypes of TC have been recognised: primary hyperphosphataemic familial TC (HFTC), primary normophosphataemic familial TC and secondary TC most commonly seen in chronic renal failure. In the absence of established treatment, management is challenging due to variable success rates with medical therapies and recurrence following surgery. AIM: We outline the successful treatment approaches in four children with TC (2 normophosphatemic TC, 2 HFTC) aged 2.5-10 years at initial presentation. CASES: Patient 1 (P1) presented at 10 years with a painless lump behind the right knee, P2 with swelling of the right knee anteriorly at 9 years, P3 and P4 with pain and swelling over the right elbow at 5 and 2.5 years respectively. All patients were of Black African-Caribbean origin and were previously reported to be fit and well with no family history of TC. RESULTS: P1, P2 had normophosphataemic TC and P3, P4 had HFTC with genetically confirmed GALNT3 mutation. All four patients had initial surgical resection with TC confirmed on histology. P1 had complete surgical resection with no recurrence at 27 months post-operatively. P2 had significant overgrowth of the tumour following surgery and was subsequently successfully managed with 25 % topical sodium metabisulphite (total duration of 8 months with a 4 month gap during which there was recurrence). P3 had post-surgical recurrence of TC on the right elbow and a new lesion on left elbow which resolved with oral acetazolamide monotherapy (15-20 mg/kg/day). P4 had recurrence of right elbow lesion following surgery and developed an extensive new hip lesion on sevelamer therapy which resolved completely with additional acetazolamide therapy (18-33 mg/kg/day). Acetazolamide was well tolerated with normal growth for 5 years in P3 and 6.5 years in P4 and no recurrence of lesions. CONCLUSION: The frequent post-surgical recurrence in TC and successful medical therapy on the other hand indicates that medical management as first line therapy should be adopted. Monotherapies with topical 25 % sodium metabisulphite in normophosphataemic and oral acetazolamide in HFTC are effective treatment strategies which are well tolerated.

Synthesis and in†vitro Metabolic Stability of Sterically Shielded Antimycobacterial Phenylalanine Amides.

Nα-aroyl-N-aryl-phenylalanine amides (AAPs) are RNA polymerase inhibitors with activity against Mycobacterium tuberculosis and non-tuberculous mycobacteria. We observed that AAPs rapidly degrade in microsomal suspensions, suggesting that avoiding hepatic metabolism is critical for their effectiveness in vivo. As both amide bonds are potential metabolic weak points of the molecule, we synthesized 16 novel AAP analogs in which the amide bonds are shielded by methyl or fluoro substituents in close proximity. Some derivatives show improved microsomal stability, while being plasma-stable and non-cytotoxic. In parallel with the metabolic stability studies, the antimycobacterial activity of the AAPs against Mycobacterium tuberculosis, Mycobacterium abscessus, Mycobacterium avium and Mycobacterium intracellulare was determined. The stability data are discussed in relation to the antimycobacterial activity of the panel of compounds and reveal that the concept of steric shielding of the anilide groups by a fluoro substituent has the potential to improve the stability and bioavailability of AAPs.

Effect of pin-to-plate atmospheric cold plasma (ACP) on microbial load and physicochemical properties in cinnamon, black pepper, and fennel.

The current study aimed to investigate the influence of pin-to-plate atmospheric cold plasma treatment (ACP) on the microbial decontamination efficacy, physical (water activity, color, texture), and bioactive (total phenolic and anti-oxidant capacity, volatile oil profile) of three major spices cinnamon, black pepper, and fennel at three different voltages (170, 200, 230 V) and exposure time (5, 10, 15 min). The surface etching and oxidative reactions of cold plasma is anticipated to cause microbial decontamination of the spices. In accordance with this, the ACP treatment significantly reduced the yeast and mold count of cinnamon, black pepper, and fennel, resulting in 1.3 Log CFU/g, 1.1 Log CFU/g, and 1.0 Log CFU/g, respectively even at the lowest treatment at 170 V-5 min. While at the highest treatment of 230 V-15 min, complete decontamination in all the samples was observed due to the plasma-induced microbial cell disruption. The water activity of samples reduced post-treatment 0.69 ± 0.02 to 0.51 ± 0.03 for cinnamon, 0.61 ± 0.03 to 0.49 ± 0.01 for pepper, and 0.60 ± 0.02 to 0.43 ± 0.02 for fennel which further reassures better microbial stability. The color and textural properties were significantly unaffected (p > 0.05) preserving the fresh-like attributes. The total phenolic content was increased for cinnamon (2.26 %), black pepper (0.11 %), and fennel (0.33 %) after plasma treatment at 230 V-15 min due to the cold plasma surface etching phenomenon. However, the essential oil composition revealed no significant variation in all three spices' control and treated samples. Thus, the study proves the potential of the atmospheric pressure cold plasma for the complete decontamination of the investigated spices (cinnamon, pepper, fennel) without remarkable changes in the volatile oil profile.

Atmospheric pressure pin-to-plate cold plasma effect on physicochemical, functional, pasting, thermal, and structural characteristics of proso-millet starch.

The present work aimed to study the influence of atmospheric pressure pin-to-plate cold plasma on the physicochemical (pH, moisture, and amylose content), functional (water & oil binding capacity, solubility & swelling power, paste clarity on storage, pasting), powder flow, thermal and structural (FTIR, XRD, and SEM) characteristics at an input voltage of 170-230 V for 5-15 min. The starch surface modification by cold plasma was seen in the SEM images which cause the surge in WBC (1.54 g/g to 1.93 g/g), OBC (2.22 g/g to 2.79 g/g), solubility (3.05-5.38% at 70 °C; 37.11-52.98% at 90 °C) and swelling power (5.39-7.83% at 70 °C; 25.67-35.33% at 90 °C) of starch. Reduction in the amylose content (27.82% to 25.07%) via plasma-induced depolymerization resists the retrogradation tendency, thereby increasing the paste clarity (up to Ì´ 39%) during the 5 days of refrigerated storage. However, the paste viscosity is reduced after cold plasma treatment yielding low-strength starch pastes. The relative crystallinity of starch increased (37.35% to 45.36%) by the plasma-induced fragmented starch granules which would aggregate and broaden the gelatinization temperature, but these starch fragments reduced the gelatinization enthalpy. The fundamental starch structure is conserved as seen in FTIR spectra. Thus, cold plasma aids in the production of soluble, low-viscous, stable, and clear paste-forming depolymerized proso-millet starch.

Blocking ADP-ribosylation expands the anti-mycobacterial spectrum of rifamycins.

The clinical utility of rifamycins against non-tuberculous mycobacterial (NTM) disease is limited by intrinsic drug resistance achieved by ADP-ribosyltransferase Arr. By blocking the site of ribosylation, we recently optimized a series of analogs with substantially improved potency against Mycobacterium abscessus. Here, we show that a representative member of this series is significantly more potent than rifabutin against major NTM pathogens expressing Arr, providing a powerful medicinal chemistry approach to expand the antimycobacterial spectrum of rifamycins. IMPORTANCE Lung disease caused by a range of different species of non-tuberculous mycobacteria (NTM) is difficult to cure. The rifamycins are very active against Mycobacterium tuberculosis, which causes tuberculosis (TB), but inactive against many NTM species. Previously, we showed that the natural resistance of the NTM Mycobacterium abscessus to rifamycins is due to enzymatic inactivation of the drug by the bacterium. We generated chemically modified versions of rifamycins that prevent inactivation by the bacterium and thus become highly active against M. abscessus. Here, we show that such a chemically modified rifamycin is also highly active against several additional NTM species that harbor the rifamycin inactivating enzyme found in M. abscessus, including M. chelonae, M. fortuitum, and M. simiae. This finding expands the potential therapeutic utility of our novel rifamycins to include several currently difficult-to-cure NTM lung disease pathogens beyond M. abscessus.

Study of the behavior and properties of frying oil on repetitive deep frying.

The current work focused on the effect of repetitive frying on the physicochemical characteristics of palm oil (PO)and sesame oil (SO) during the preparation of french fries by deep fat frying. A total of 16 frying cycles were carried out and the effect on various parameters was evaluated. The repetitive frying caused higher damage to sesame oil as compared with PO as observed from changes in FFA and PV which increased to 0.63 ± 0.12, 1.31 ± 0.16%, and 2.71 ± 0.02, 7.21 ± 0.01 meq/kg from an initial value of 0.28 ± 0.00, 0.93 ± 0.16% and 0.19 ± 0.00, 0.71 ± 0.00 meq/kg for PO, SO respectively. The fatty acid composition of SO showed significant change with a decrease in linoleic acid and oleic acid content from 42.7 ± 0.01 to 28.1 ± 0.03 and 36.2 ± 0.01 to 25.1 ± 0.01 after 16 frying cycles respectively. The oleic acid content of PO was less affected it decreased from an initial value of 42.4 ± 0.01 to 38.9 ± 0.01 after 16 cycles. The fatty acid composition of PO made it more stable to the repetitive frying process. The physical properties like density refractive index and viscosity of SO were badly affected by repetitive frying. The french fries fried in PO score higher overall acceptability in the sensory examination. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05774-4.

ADP-ribosylation-resistant rifabutin analogs show improved bactericidal activity against drug-tolerant M. abscessus in caseum surrogate.

Necrotic lesions and cavities filled with caseum are a hallmark of mycobacterial pulmonary disease. Bronchocavitary Mycobacterium abscessus disease is associated with poor treatment outcomes. In caseum surrogate, M. abscessus entered an extended stationary phase showing tolerance to killing by most current antibiotics, suggesting that caseum persisters contribute to the poor performance of available treatments. Novel ADP-ribosylation-resistant rifabutin analogs exhibited bactericidal activity against these M. abscessus persisters at concentrations achievable by rifamycins in caseum.

Surface-Engineered Extracellular Vesicles in Cancer Immunotherapy.

Extracellular vesicles (EVs) are lipid bilayer-enclosed bodies secreted by all cell types. EVs carry bioactive materials, such as proteins, lipids, metabolites, and nucleic acids, to communicate and elicit functional alterations and phenotypic changes in the counterpart stromal cells. In cancer, cells secrete EVs to shape a tumor-promoting niche. Tumor-secreted EVs mediate communications with immune cells that determine the fate of anti-tumor therapeutic effectiveness. Surface engineering of EVs has emerged as a promising tool for the modulation of tumor microenvironments for cancer immunotherapy. Modification of EVs' surface with various molecules, such as antibodies, peptides, and proteins, can enhance their targeting specificity, immunogenicity, biodistribution, and pharmacokinetics. The diverse approaches sought for engineering EV surfaces can be categorized as physical, chemical, and genetic engineering strategies. The choice of method depends on the specific application and desired outcome. Each has its advantages and disadvantages. This review lends a bird's-eye view of the recent progress in these approaches with respect to their rational implications in the immunomodulation of tumor microenvironments (TME) from pro-tumorigenic to anti-tumorigenic ones. The strategies for modulating TME using targeted EVs, their advantages, current limitations, and future directions are discussed.

Effect of atmospheric pin-to-plate cold plasma on oat protein: Structural, chemical, and foaming characteristics.

The impact of novel pin-to-plate atmospheric cold plasma was investigated with input voltage (170 V, 230 V) and exposure time (15 & 30 min) on oat protein by studying structural (FTIR, circular dichroism (CD), UV-vis, Fluorescence), morphological (particle size analysis, SEM, turbidity), chemical (pH, redox potential (ORP), ζ potential, carbonyl, sulfhydryl, surface hydrophobicity), and foaming characteristics. The plasma treatment reduced the pH while increasing the ORP of the dispersions. These ionic environment changes affected the ζ potential and particle size leading to the formation of larger aggregates (170-15; 230-15) and distorted smaller ones (170-30; 230-30) as confirmed by SEM. The FTIR spectra showed reduced intensity at specific amide bands (1600-1700 cm-1) and also an increase in carbonyl stretching (1743 cm-1) representing oxidative carbonylation (increase in carbonyl content). Thus, the partial exposure of hydrophobic amino acids increases surface hydrophobicity. The altered secondary structure (rise in α-helix, decrement in ß-sheets and turns), and tertiary structures were observed in circular dichroism (CD) and UV absorbance and fluorescence characteristics of proteins respectively. Furthermore, the increase in free sulfhydryl content and disulfide content was highly affected by the plasma treatments due to observed protein unfolding and aggregations. Besides, the increased solubility and reduced surface tension contributed to the improved foaming characteristics. Thus, plasma processing influences protein structure affecting their characteristics and other functionalities.

Effects of pin-to-plate atmospheric cold plasma for modification of pearl millet (Pennisetum glaucum) starch.

The present study was done to analyze the effect of atmospheric pressure non-thermal pin-to-plate plasma at a range of different voltages (170, 200, and 230V) at different time intervals (10, 20, and 30 mins) on under-utilized pearl millet starch. The untreated and treated starches were analyzed for amylose content, pH, carbonyl, and carboxyl group, reducing sugar, turbidity, water, and oil binding property, pasting property, DSC, FTIR, XRD, and molecular weight. As cold plasma contains highly reactive species and free radicals, it is expected to cause noticeable modifications in the attributes of treated starch. There has been a significant reduction (p < 0.05) in turbidity value by 38.97% and pH value of starch from 6.49 to 4.05. Plasma-treated samples produced clearer pastes with higher stability over storage time. Cold plasma treatment also led to an increase in the ζ potential. However, there has been no significant change in the water activity and oil-binding capacity of the starch. Reducing sugar content, average molecular weight, degree of polymerization, pasting property, XRD, and FTIR data confirmed that cross-linking takes place in samples treated at lower voltages and lesser time followed by depolymerization occurring in harshly treated plasma samples. The study thus points out the possible use of cold plasma for starch modification to produce starches with altered properties.

Synthesis and Characterization of Phenylalanine Amides Active against Mycobacterium abscessus and Other Mycobacteria.

Nα-2-thiophenoyl-d-phenylalanine-2-morpholinoanilide [MMV688845, Pathogen Box; Medicines for Malaria Venture; IUPAC: (2R)-N-(1-((2-morpholinophenyl)amino)-1-oxo-3-phenylpropan-2-yl)thiophene-2-carboxamide)] is a hit compound, which shows activity against Mycobacterium abscessus (MIC90 6.25-12.5 µM) and other mycobacteria. This work describes derivatization of MMV688845 by introducing a thiomorpholine moiety and the preparation of the corresponding sulfones and sulfoxides. The molecular structures of three analogs are confirmed by X-ray crystallography. Conservation of the essential R configuration during synthesis is proven by chiral HPLC for an exemplary compound. All analogs were characterized in a MIC assay against M. abscessus, Mycobacterium intracellulare, Mycobacterium smegmatis, and Mycobacterium tuberculosis. The sulfone derivatives exhibit lower MIC90 values (M. abscessus: 0.78 µM), and the sulfoxides show higher aqueous solubility than the hit compound. The most potent derivatives possess bactericidal activity (99% inactivation of M. abscessus at 12.5 µM), while they are not cytotoxic against mammalian cell lines.

Activity of Oral Tebipenem-Avibactam in a Mouse Model of Mycobacterium abscessus Lung Infection.

The combination of the ß-lactam tebipenem and the ß-lactamase inhibitor avibactam shows potent bactericidal activity against Mycobacterium abscessus in vitro. Here, we report that the combination of the respective oral prodrugs tebipenem-pivoxil and avibactam ARX-1796 showed efficacy in a mouse model of M. abscessus lung infection. The results suggest that tebipenem-avibactam presents an attractive oral drug candidate pair for the treatment of M. abscessus pulmonary disease and could inform the design of clinical trials.

Rheological performance of film-forming solutions and barrier properties of films fabricated from cold plasma-treated high methoxyl apple pectin and crosslinked by Ca2+: Impact of plasma treatment voltage.

Sustainable and "green" technologies, such as cold plasma are gaining attention in recent times for improving the functional properties of hydrocolloids. Chemical modifications of hydrocolloids require several chemicals and solvents, which are not environment-friendly. The major objective of the study was to understand the impact of plasma treatment (170-230 V|15 min) on the rheology of film-forming solutions (FFS) and the barrier properties of pectin films. The film-forming properties of plasma-treated pectin were investigated in the presence of two plasticizers, namely, glycerol and polyethylene glycol (PEG) 400. The effects of cross-linking by CaCl2 on the rheology of FFS and barrier properties of the films were discussed. A voltage-dependent decrease in the apparent viscosity of FFS was observed. The viscoelastic properties of the FFS were enhanced due to cross-linking. Glycerol exhibited a better plasticizing effect than PEG. Cross-linking and increasing voltage synergistically contributed towards lower oxygen and carbon dioxide transmission rates. The moisture sorption rate and capacity of the films increased with the voltage of the treatment. The resistance to extension of the films made from glycerol and PEG decreased with voltage, with no significant change in extensibility. On the other hand, the cross-linking by Ca2+ and plasma treatment enhanced the resistance to extension for the films made from both the plasticizers. While the increasing hydrophilicity and opacity of the films were a major drawback of plasma modification, the increase in UV barrier property of the films was an advantage of the modification.

Integrative transcriptomic analysis of the amyotrophic lateral sclerosis spinal cord implicates glial activation and suggests new risk genes.

Amyotrophic lateral sclerosis (ALS) is a progressively fatal neurodegenerative disease affecting motor neurons in the brain and spinal cord. In this study, we investigated gene expression changes in ALS via RNA sequencing in 380 postmortem samples from cervical, thoracic and lumbar spinal cord segments from 154 individuals with ALS and 49 control individuals. We observed an increase in microglia and astrocyte gene expression, accompanied by a decrease in oligodendrocyte gene expression. By creating a gene co-expression network in the ALS samples, we identified several activated microglia modules that negatively correlate with retrospective disease duration. We mapped molecular quantitative trait loci and found several potential ALS risk loci that may act through gene expression or splicing in the spinal cord and assign putative cell types for FNBP1, ACSL5, SH3RF1 and NFASC. Finally, we outline how common genetic variants associated with splicing of C9orf72 act as proxies for the well-known repeat expansion, and we use the same mechanism to suggest ATXN3 as a putative risk gene.

Triglycerides of medium-chain fatty acids: a concise review.

Medium-chain triglycerides contain medium-chain fatty acid esterified to the glycerol backbone. These MCFA have a shorter chain length and are quickly metabolized in the body serving as an immediate energy source. They are known to have good physiological as well as functional characteristics which help in treating various health disorders. Naturally, they are found in coconut oil, milk fat, and palm kernel oil, and they are synthetically produced by esterification and interesterification reactions. Due to their numerous health benefits, MCT is used as a functional or nutraceutical oil in various food and pharmaceutical formulations. To increase their nutraceutical benefits and food applications MCFA can be used along with polyunsaturated fatty acids in the synthesis of structured lipids. This review aims to provide information about triglycerides of MCFA, structure, metabolism, properties, synthetic routes, intensified synthesis approaches, health benefits, application, and safety of use of MCT in the diet.

A Leucyl-tRNA Synthetase Inhibitor with Broad-Spectrum Anti-Mycobacterial Activity.

Global infections by non-tuberculous mycobacteria (NTM) are steadily rising. New drugs are needed to treat NTM infections, but the NTM drug pipeline remains poorly populated and focused on repurposing or reformulating approved antibiotics. We sought to accelerate de novo NTM drug discovery by testing advanced compounds with established activity against Mycobacterium tuberculosis 3-aminomethyl 4-halogen benzoxaboroles, a novel class of leucyl-tRNA synthetase inhibitors, were recently discovered as active against M. tuberculosis Here, we report that the benzoxaborole EC/11770 is not only a potent anti-tubercular agent but is active against the M. abscessus and M. avium complexes. Focusing on M. abscessus, which causes the most difficult-to-cure NTM disease, we show that EC/11770 retained potency against drug-tolerant biofilms in vitro and was effective in a mouse lung infection model. Resistant mutant selection experiments showed a low frequency of resistance and confirmed leucyl-tRNA synthetase as the target. This work establishes the benzoxaborole EC/11770 as a novel preclinical candidate for the treatment of NTM lung disease and tuberculosis and validates leucyl-tRNA synthetase as an attractive target for the development of broad-spectrum anti-mycobacterials.

Acute haemorrhagic necrotizing encephalopathy associated with COVID-19 in a patient with liver cirrhosis.

COVID-19 is emerging as a global pandemic and is a complex disease presenting with multi-organ involvement. Acute haemorrhagic necrotizing encephalopathy (AHNE) is a rarely reported phenomenon post-COVID-19 but is a rapidly progressing, fatal, haemorrhagic necrosis of the CNS parenchyma. Here, we present a very interesting case of a cirrhotic male patient with AHNE with COVID-19. Diagnosis of AHNE requires a multimodality approach and high index of suspicion in a patient suffering from SARS-CoV-2. Timely intervention and diagnosis may lead to a favourable outcome in the diagnosed cases. Future detailed studies in this direction may give an insight into this rare but important disease entity.