Mitochondria-Targeted Oligomeric α-Synuclein Induces TOM40 Degradation and Mitochondrial Dysfunction in Parkinson's Disease and Parkinsonism-Dementia of Guam.

Mitochondrial dysfunction is a central aspect of Parkinson's disease (PD) pathology, yet the underlying mechanisms are not fully understood. This study investigates the link between α-Synuclein (α-Syn) pathology and the loss of translocase of the outer mitochondrial membrane 40 (TOM40), unraveling its implications for mitochondrial dysfunctions in neurons. We discovered that TOM40 protein depletion occurs in the brains of patients with Guam Parkinsonism Dementia (Guam PD) and cultured neurons expressing α-Syn proteinopathy, notably, without corresponding changes in TOM40 mRNA levels. Cultured neurons expressing α-Syn mutants, with or without a mitochondria-targeting signal (MTS) underscore the role of α-Syn's mitochondrial localization in inducing TOM40 degradation. Parkinson's Disease related etiological factors, such as 6-hydroxy dopamine or ROS/metal ions stress, which promote α-Syn oligomerization, exacerbate TOM40 depletion in PD patient-derived cells with SNCA gene triplication. Although α-Syn interacts with both TOM40 and TOM20 in the outer mitochondrial membrane, degradation is selective for TOM40, which occurs via the ubiquitin-proteasome system (UPS) pathway. Our comprehensive analyses using Seahorse technology, mitochondrial DNA sequencing, and damage assessments, demonstrate that mutant α-Syn-induced TOM40 loss results in mitochondrial dysfunction, characterized by reduced membrane potential, accumulation of mtDNA damage, deletion/insertion mutations, and altered oxygen consumption rates. Notably, ectopic supplementation of TOM40 or reducing pathological forms of α-Syn using ADP-ribosylation inhibitors ameliorate these mitochondrial defects, suggesting potential therapeutic avenues. In conclusion, our findings provide crucial mechanistic insights into how α-Syn accumulation leads to TOM40 degradation and mitochondrial dysfunction, offering insights for targeted interventions to alleviate mitochondrial defects in PD.

Vanillin/fungal-derived carboxy methyl chitosan/polyvinyl alcohol hydrogels prepared by freeze-thawing for wound dressing applications.

In this study, we developed hydrogels using polyvinyl alcohol (PVA), vanillin (V), and a fungus-derived carboxymethyl chitosan (FC) using a freeze-thaw-based method. These hydrogels were strengthened by bonding, including Schiff's base bonding between V and FC and hydrogen bonding between PVA, FC, and V. The physiological properties of these PFCV hydrogels were characterized by FTIR, TGA, compressive mechanical testing, and rheology and water contact angle measurements. FTIR spectra confirmed the effective integration of FC and V into the PVA network. TGA results showed that FC and V enhanced the thermal stability of PFCV hydrogels. Mechanical tests showed increasing the amount of V reduced mechanical properties but did not alter the elastic character of hydrogels. SEM images displayed a well-interconnected porous structure with excellent swelling capacity. In addition, we examined biological properties using cell-based in vitro studies and performed antibacterial assessments to assess suitability for potential wound dressing applications. Prestoblue™ and live/dead cell analysis strongly supported skin fibroblast attachment and viability, DPPH assays indicated substantial antioxidant activity, and PFCV hydrogels showed enhanced antibacterial effects against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). In summary, incorporating V and FC into PVA hydrogels appears to be attractive for wound dressing applications.

Endogenous TDP-43 mislocalization in a novel knock-in mouse model reveals DNA repair impairment, inflammation, and neuronal senescence.

TDP-43 mislocalization and aggregation are key pathological features of motor neuron diseases (MND) including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, transgenic hTDP-43 WT or ΔNLS-overexpression animal models mainly capture late-stages TDP-43 proteinopathy, and do not provide a complete understanding of early motor neuron-specific pathology during pre-symptomatic phases. We have now addressed this shortcoming by generating a new endogenous knock-in (KI) mouse model using a combination of CRISPR/Cas9 and FLEX Cre-switch strategy for the conditional expression of a mislocalized Tdp-43ΔNLS variant of mouse Tdp-43. This variant is either expressed conditionally in whole mice or specifically in the motor neurons. The mice exhibit loss of nuclear Tdp-43 concomitant with its cytosolic accumulation and aggregation in targeted cells, leading to increased DNA double-strand breaks (DSBs), signs of inflammation and DNA damage-associated cellular senescence. Notably, unlike WT Tdp43 which functionally interacts with Xrcc4 and DNA Ligase 4, the key DSB repair proteins in the non-homologous end-joining (NHEJ) pathway, the Tdp-43ΔNLS mutant sequesters them into cytosolic aggregates, exacerbating neuronal damage in mice brain. The mutant mice also exhibit myogenic degeneration in limb muscles and distinct motor deficits, consistent with the characteristics of MND. Our findings reveal progressive degenerative mechanisms in motor neurons expressing endogenous Tdp-43ΔNLS mutant, independent of TDP-43 overexpression or other confounding etiological factors. Thus, this unique Tdp-43 KI mouse model, which displays key molecular and phenotypic features of Tdp-43 proteinopathy, offers a significant opportunity to further characterize the early-stage progression of MND and also opens avenues for developing DNA repair-targeted approaches for treating TDP-43 pathology-linked neurodegenerative diseases.

Source Localization and Spectrum Analyzing of EEG in Stuttering State upon Dysfluent Utterances.

Purpose: The present study which addressed adults who stutter (AWS) attempted to investigate power spectral dynamics in the stuttering state by answering the questions using quantitative electroencephalography (qEEG). Method: A 64-channel electroencephalography (EEG) setup was used for data acquisition at 20 AWS. Since the speech, especially stuttering, causes significant noise in the EEG, 2 conditions of speech preparation (SP) and imagined speech (IS) were considered. EEG signals were decomposed into 6 bands. The corresponding sources were localized using the standard low-resolution electromagnetic tomography (sLORETA) tool in both fluent and dysfluent states. Results: Significant differences were noted after analyzing the time-locked EEG signals in fluent and dysfluent utterances. Consistent with previous studies, poor alpha and beta suppression in SP and IS conditions were localized in the left frontotemporal areas in a dysfluent state. This was partly true for the right frontal regions. In the theta range, disfluency was concurrence with increased activation in the left and right motor areas. Increased delta power in the left and right motor areas as well as increased beta2 power over left parietal regions was notable EEG features upon fluent speech. Conclusion: Based on the present findings and those of earlier studies, explaining the neural circuitries involved in stuttering probably requires an examination of the entire frequency spectrum involved in speech.

Comparison of Adsorption Performance of Biochar Derived from Urban Biowaste Materials for Removal of Heavy Metals.

This study investigated the adsorption performance of biochar produced from different types of urban biowaste material viz., sugarcane bagasse (SB), brinjal stem (BS), and citrus peel (CP) for removal of heavy metal ions (Pb, Cu, Cr, and Cd) from aqueous solution. The effects of biowaste material, dosage of biochar, solution pH, and initial concentration of heavy metal ions and isotherm models were performed to understand the possible adsorption mechanisms. The results showed that the biochar derived from BS and SB removes Cu (99.94%), Cr (99.57%), and Cd (99.77%) whereas biochar derived from CP removes Pb (99.59%) and Cu (99.90%) more efficiently from the aqueous solution. Biochar derived from BS showed maximum adsorption capacity for Cu (246.31 mg g-1), Pb (183.15 mg g-1), and Cr (71.89 mg g-1) while the biochar derived from CP showed highest for Cd (15.46 mg g-1). Moreover, biochar derived from BS and SB has more polar functional groups and less hydrophobicity than the biochar derived from CP. This study reveals that solution pH and biochar doses play a major role in removal of heavy metal ions from aqueous solution. The results of Langmuir model fitted well for Pb and Cu while the Freundlich model for Cr and Cd. Our study concludes that the biochar derived from different biowaste materials adsorbs heavy metal ions majorly through surface complexation and precipitation processes. The results of this study will be very useful in selecting the effective urban biowaste material for making biochar for heavy metal removal from the aqueous environment.

Tetrahydrocurcumin Derivatives Enhanced the Anti-Inflammatory Activity of Curcumin: Synthesis, Biological Evaluation, and Structure-Activity Relationship Analysis.

Tetrahydrocurcumin, the most abundant curcumin transformation product in biological systems, can potentially be a new alternative therapeutic agent with improved anti-inflammatory activity and higher bioavailability than curcumin. In this article, we describe the synthesis and evaluation of the anti-inflammatory activities of tetrahydrocurcumin derivatives. Eleven tetrahydrocurcumin derivatives were synthesized via Steglich esterification on both sides of the phenolic rings of tetrahydrocurcumin with the aim of improving the anti-inflammatory activity of this compound. We showed that tetrahydrocurcumin (2) inhibited TNF-α and IL-6 production but not PGE2 production. Three tetrahydrocurcumin derivatives inhibited TNF-α production, five inhibited IL-6 production, and three inhibited PGE2 production. The structure-activity relationship analysis suggested that two factors could contribute to the biological activities of these compounds: the presence or absence of planarity and their structural differences. Among the tetrahydrocurcumin derivatives, cyclic compound 13 was the most active in terms of TNF-α production, showing even better activity than tetrahydrocurcumin. Acyclic compound 11 was the most effective in terms of IL-6 production and retained the same effect as tetrahydrocurcumin. Moreover, acyclic compound 12 was the most active in terms of PGE2 production, displaying better inhibition than tetrahydrocurcumin. A 3D-QSAR analysis suggested that the anti-inflammatory activities of tetrahydrocurcumin derivatives could be increased by adding bulky groups at the ends of compounds 2, 11, and 12.

Single thermal scan digital system for deep level transient spectroscopy.

We have developed a micro-controller based Deep Level Transient Spectroscopy (DLTS) system to identify the deep-level defects in semiconductors. It consists of Arduino-Due, a capacitance meter, and interface circuits. In addition, we have also developed the algorithms needed for the entire signal processing. It is not limited to Arduino-Due but can be implemented using other micro-controllers also. We have used Arduino-Due to generate the filling pulse and monitor the capacitance, temperature, data acquisition, timing control, and signal processing. The sequence of generating the filling pulse, reading the data, and signal processing is controlled digitally rather than by analog sampling circuits and timers. The minimum pulse width generated using Arduino-Due is 50 ns; the pulse width generation depends on various hardware and software parameters and their integration. The resolution in reading the data is 0.8 mV/unit. The time delays in reading the data are appropriately taken care of in the system. The whole experiment can be completed in a single temperature cycle within 2-3 h. The system is simple, inexpensive, in an easy-to-use platform, and less time-consuming; minimizes possible errors; and improves accuracy. The measurements using the "micro-controller based DLTS system" are verified by fabricating (Au) gold-doped silicon (Si) p-n junction samples (Au is a well-understood defect in Si). Using the Arduino-Due based DLTS system, we calculated the energy, the capture cross section, and the concentration of trap levels. The results are in good agreement with the literature, indicating the versatility of the system.

Novel, Biosynthesis of Palladium Nanoparticles using Strychnos Potatorum Polysaccharide as a Green sustainable approach; and their effective Catalytic Hydrogenation of 4-Nitrophenol.

In the current study, we successfully used strychnos potatorum polysaccharide through autoclaving to synthesize palladium nanoparticles in a green, sustainable process. These polysaccharide act as a stabilizing, capping, and reducing agent. It also used various analytical characterizations, including UV-Visible spectroscopy, FT-IR spectroscopy, X-Ray diffraction (XRD), Scanning electron microscopy (FE-SEM), EDAX, and X-ray photoelectron spectroscopy (XPS), TEM and gel permeation chromatography (GPC) are used to analyze biosynthesized pallidum nanoparticles (PdNPs). The surface plasmon resonance (SPR) band at 276 nm and UV-visible spectroscopy revealed the presence of the generated PdNPs. The XRD data show that PdNPs have crystalline behavior and a pristine face-centered cubic (FCC) structure. The PdNPs were successfully developed by catalytic reduction of 4-nitrophenol (4-NP). The catalytic activity and reusability of the environmentally friendly PdNPs catalyst were demonstrated by achieving a remarkable transformation of 95 % nitrophenol to 4-aminophenol after five cycles. The reaction rate constant (k) for the degradation of 4-nitrophenol (4-NP) using SP-PdNPs as a catalyst is 0.1201 min-1 and R2 0.9867, with a normalized rate constant of (Knor = K/m) of 7.206 s-1 mM-1. These findings provide fundamental knowledge of the catalytic process governing the hydrogenation of p-nitrophenol, which will help designers of effective catalysts. An innovative and affordable technique for creating PdNPs that are environmentally acceptable and can be utilized as effective catalysts in environmental applications is the use of strychnos potatorum gum polysaccharide. The green-synthesized PdNPs can be used for pollutant remediation, including pharmaceutical, domestic, heavy metal, industrial, and pesticide pollutants.

Comparison of Cost and Potency of Human Mesenchymal Stromal Cell Conditioned Medium Derived from 2- and 3-Dimensional Cultures.

Mesenchymal stromal cell (MSC)-derived products, such as trophic factors (MTFs), have anti-inflammatory properties that make them attractive for cell-free treatment. Three-dimensional (3D) culture can enhance these properties, and large-scale expansion using a bioreactor can reduce manufacturing costs. Three lots of MTFs were obtained from umbilical cord MSCs produced by either monolayer culture (Monol MTF) or using a 3D microcarrier in a spinner flask dynamic system (Bioreactor MTF). The resulting MTFs were tested and compared using anti-inflammatory potency assays in two different systems: (1) a phytohemagglutinin-activated peripheral blood mononuclear cell (PBMNC) system and (2) a lipopolysaccharide (LPS)-activated macrophage system. Cytokine expression by macrophages was measured via RT-PCR. The production costs of hypothetical units of anti-inflammatory effects were calculated using the percentage of TNF-α inhibition by MTF exposure. Bioreactor MTFs had a higher inhibitory effect on TNF (p < 0.01) than monolayer MTFs (p < 0.05). The anti-inflammatory effect of Bioreactor MTFs on IL-1ß, TNF-α, IL-8, IL-6, and MIP-1 was significantly higher than that of monolayer MTFs. The production cost of 1% inhibition of TNF-α was 11-40% higher using monolayer culture compared to bioreactor-derived MTFs. A 3D dynamic culture was, therefore, able to produce high-quality MTFs, with robust anti-inflammatory properties, more efficiently than monolayer static systems.

Antimicrobial Efficacy of Blended Essential Oil and Chlorhexidine against Periodontal Pathogen (P.gingivalis)-An In Vitro Study.

Background: Essential oils (EOs) have a considerable amount of therapeutic and preventive effect in treating dental diseases due to their wider potential as antibacterial and anti-inflammatory agents. EOs like virgin coconut oil, eucalyptus oil, peppermint oil thyme oil, and clove oil, when used in combination, may further have enhanced antimicrobial effects. However, limited information exists on the synergistic effect of these oils when used in combination, especially on the primary periodontal pathogen Porphyromonas gingivalis. Aim: The current study aims to compare the antimicrobial efficacy of commercially available EO on the periodontal pathogen, P. gingivalis, in comparison to chlorhexidine (CHX). Materials and Methods: Antimicrobial efficacy of EO and CHX was assessed at various concentrations against the periodontal pathogen P. gingivalis, by evaluating the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results: P. gingivalis was seen to be sensitive at a MIC of 100 µg/ml and 50 µg/ml concentration of the EO, which is regarded as the MIC of EO against P. gingivalis and CHX effectively inhibited microbial growth at 0.4 µg/ml. Conclusion: A combination of EOs possesses a potent antibacterial activity against P. gingivalis, and the antibacterial efficacy increases with increasing concentration of EOs.

Patterns and determinants of soil CO2 efflux in major forest types of Central Himalayas, India.

Soil CO2 efflux (Fsoil) is a significant contributor of labile CO2 to the atmosphere. The Himalayas, a global climate hotspot, condense several climate zones on account of their elevational gradients, thus, creating an opportunity to investigate the Fsoil trends in different climate zones. Presently, the studies in the Indian Himalayan region are localized to a particular forest type, climate zone, or area of interest, such as seasonal variation. We used a portable infrared gas analyzer to investigate the Fsoil rates in Himalayan tropical to alpine scrub forest along a 3100-m elevational gradient. Several study parameters such as seasons, forest types, tree species identity, age of trees, distance from tree base, elevation, climatic factors, and soil physico-chemical and enzymatic parameters were investigated to infer their impact on Fsoil regulation. Our results indicate the warm and wet rainy season Fsoil rates to be 3.8 times higher than the cold and relatively dry winter season. The tropical forest types showed up to 11 times higher Fsoil rates than the alpine scrub forest. The temperate Himalayan blue pine and tropical dipterocarp sal showed significant Fsoil rates, while the alpine Rhododendron shrubs the least. Temperature and moisture together regulate the rainy season Fsoil maxima. Spatially, Fsoil rates decreased with distance from the tree base (ρ = - 0.301; p < 0.0001). Nepalese alder showed a significant positive increase in Fsoil with stem girth (R2 = 0.7771; p = 0.048). Species richness (r, 0.81) and diversity (r, 0.77) were significantly associated with Fsoil, while elevation and major edaphic properties showed a negative association. Surface litter inclusion presented an elevation-modulated impact. Temperature sensitivity was exorbitantly higher in the sub-tropical pine (Q10, 11.80) and the alpine scrub (Q10, 9.08) forests. We conclude that the rise in atmospheric temperature and the reduction in stand density could enhance the Fsoil rates on account of increased temperature sensitivity.

Different GCMs yet similar outcome: predicting the habitat distribution of Shorea robusta C.F. Gaertn. in the Indian Himalayas using CMIP5 and CMIP6 climate models.

Climate change impact on the habitat distribution of umbrella species presents a critical threat to the entire regional ecosystem. This is further perilous if the species is economically important. Sal (Shorea robusta C.F. Gaertn.), a climax forest forming Central Himalayan tree species, is one of the most valuable timber species and provides several ecological services. Sal forests are under threat due to over-exploitation, habitat destruction, and climate change. Sal's poor natural regeneration and its unimodal density-diameter distribution in the region illustrate the peril to its habitat. We, modelled the current as well as future distribution of suitable sal habitats under different climate scenarios using 179 sal occurrence points and 8 bioclimatic environmental variables (non-collinear). The CMIP5-based RCP4.5 and CMIP6-based SSP245 climate models under 2041-2060 and 2061-2080 periods were used to predict the impact of climate change on sal's future potential distribution area. The niche model results predict the mean annual temperature and precipitation seasonality as the most influential sal habitat governing variables in the region. The current high suitability region for sal was 4.36% of the total geographic area, which shows a drastic decline to 1.31% and 0.07% under SSP245 for 2041-60 and 2061-80, respectively. The RCP-based models predicted more severe impact than SSP; however, both RCP and SSP models showed complete loss of high suitability regions and overall shift of species northwards in the Uttarakhand state. We could identify the current and future suitable habitats for conserving sal population through assisted regeneration and management of other regional issues.

Polyphenols with Anti-Inflammatory Properties: Synthesis and Biological Activity of Novel Curcumin Derivatives.

Herein, we describe the synthesis and evaluation of anti-inflammatory activities of new curcumin derivatives. The thirteen curcumin derivatives were synthesized by Steglich esterification on one or both of the phenolic rings of curcumin with the aim of providing improved anti-inflammatory activity. Monofunctionalized compounds showed better bioactivity than the difunctionalized derivatives in terms of inhibiting IL-6 production, and known compound 2 presented the highest activity. Additionally, this compound showed strong activity against PGE2. Structure-activity relationship studies were carried out for both IL-6 and PGE2, and it was found that the activity of this series of compounds increases when a free hydroxyl group or aromatic ligands are present on the curcumin ring and a linker moiety is absent. Compound 2 remained the highest activity in modulating IL-6 production and showed strong activity against PGE2 synthesis.

Deep learning model for predicting tunnel damages and track serviceability under seismic environment.

Jammu and Kashmir in the northwestern part of the Himalayan region is frequently triggered with moderate to large magnitude earthquakes due to an active tectonic regime. In this study, a mathematical formulation-based Seismic Tunnel Damage Prediction (STDP) model is proposed using the deep learning (DL) approach. The pertinency of the DL model is validated using tunnel damage data from historical earthquakes such as the 1999 Chi-Chi earthquake, the 2004 Mid-Niigata earthquake, and the 2008 Wenchuan earthquake. Peak ground acceleration (PGA), source to site distance (SSD), overburden depth (OD), lining thickness (t), tunnel diameter (Ф), and geological strength index (GSI) were employed as inputs to train the Feedforward Neural Network (FNN) for damage state prediction. The performance evaluation results provided a clear indication for further use in a variety of risk assessment domains. When compared to models based on historical data, the proposed STDP model produces consistent results, demonstrating the robustness of the methodology used in this work. All models perform well during validation based on fitness metrics. The "STD multiple graphs" is also proposed which provide information on damage indexing, damage pattern, and crack predictive specifications. This can be used as a ready toolbox to check the vulnerability in post-seismic scenarios. The seismic design guidelines for tunnelling projects are also proposed, which discuss the damage pattern and suggest mitigation measures. The proposed STDP model, STD multiple graphs, and seismic design guidance are applicable to any earthquake-prone tunnelling project anywhere in the world.

ROS-generating, pH-responsive and highly tunable reduced graphene oxide-embedded microbeads showing intrinsic anticancer properties and multi-drug co-delivery capacity for combination cancer therapy.

The development of effective carriers enabling combination cancer therapy is of practical importance due to its potential to enhance the effectiveness of cancer treatment. However, most of the reported carriers are monofunctional in nature. The carriers that can be applied to concomitantly mediate multiple treatment modalities are highly deficient. This study fills this gap by reporting the design and fabrication of ROS-generating carbohydrate-based pH-responsive beads with intrinsic anticancer therapy and multidrug co-delivery capacity for combination cancer therapy. Sodium alginate (SA) microspheres and reduced graphene oxide (rGO)-embedded chitosan (CS) beads are developed via emulsion-templated ionic gelation for a combination therapy involving co-delivery of curcumin (CUR) and 5-fluororacil (5-FU). Drug-encapsulated microbeads are characterized by FTIR, DSC, TGA, XRD, and SEM. 5-FU and CUR-encapsulated microbeads are subjected to in vitro drug release studies at pH 6.8 and 1.2 at 37 °C. Various release kinetic parameters are evaluated. The results show that the Korsmeyer-Peppas model and non-Fickian release kinetics are best suited. The microspheres and microbeads are found to effectively act against MCF7 cells and show intrinsic anticancer capacity. These results indicate the promising performance of our beads in mediating combination drug therapy to improve the effectiveness of cancer treatment.

SARS-CoV-2 and the central nervous system: Emerging insights into hemorrhage-associated neurological consequences and therapeutic considerations.

Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to impact our lives by causing widespread illness and death and poses a threat due to the possibility of emerging strains. SARS-CoV-2 targets angiotensin-converting enzyme 2 (ACE2) before entering vital organs of the body, including the brain. Studies have shown systemic inflammation, cellular senescence, and viral toxicity-mediated multi-organ failure occur during infectious periods. However, prognostic investigations suggest that both acute and long-term neurological complications, including predisposition to irreversible neurodegenerative diseases, can be a serious concern for COVID-19 survivors, especially the elderly population. As emerging studies reveal sites of SARS-CoV-2 infection in different parts of the brain, potential causes of chronic lesions including cerebral and deep-brain microbleeds and the likelihood of developing stroke-like pathologies increases, with critical long-term consequences, particularly for individuals with neuropathological and/or age-associated comorbid conditions. Our recent studies linking the blood degradation products to genome instability, leading to cellular senescence and ferroptosis, raise the possibility of similar neurovascular events as a result of SARS-CoV-2 infection. In this review, we discuss the neuropathological consequences of SARS-CoV-2 infection in COVID survivors, focusing on possible hemorrhagic damage in brain cells, its association to aging, and the future directions in developing mechanism-guided therapeutic strategies.

Strychnos Potatorum L. Seed Polysaccharide-Based Stimuli-Responsive Hydrogels and Their Silver Nanocomposites for the Controlled Release of Chemotherapeutics and Antimicrobial Applications.

Natural Strychnos potatorum L. (SPL) polysaccharide-based dual-responsive semi-IPN-type (SPL-DMA) hydrogels have been fabricated using dimethylaminoethyl methacrylate by simple free radical polymerization. Furthermore, a facial and eco-friendly method has been developed for the green synthesis of silver nanoparticles on SPL-DMA hydrogel templates (SPL-DMA-Ag) using an aqueous leaf extract of Carissa spinarum (as a bioreducing agent). SPL-DMA and SPL-DMA-Ag were characterized using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetry analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and evaluated network parameters. 5-Fluorouracil and doxorubicin were successfully encapsulated, and in vitro drug release studies were performed at pH values of 1.2 and 7.4 and at 25 and 37 °C. To understand the drug release mechanism of SPL-DMA hydrogels, various kinetic parameters were calculated. Biocompatibility and anticancer activities of SPL-DMA hydrogels were proved by an antioxidant activity study and in vitro cell viability studies against HeLa and 3T3-L1 cell lines. SPL-DMA-Ag hydrogels were used for antibacterial application.

Pouteria sapota (Red Mamey Fruit): Chemistry and Biological Activity of Carotenoids.

BACKGROUND: Red mamey is the fruit of P. sapota, a tree found in Mesoamerica and Asia. This fruit is considered a nutraceutical due to its multiple beneficial health including antiamyloidogenic activity and potential anti-tumorigenic property. Red mamey contain a variety of carotenoids including novel ketocarotenoids such as sapotexanthin and cryptocapsin. A ketocarotenoid is a chemical compound with a carbonyl group present in the ß-ring or in the double bond chain of a carotenoid. In red mamey, the 3'-deoxy-k-end group in sapotexanthin has proven to be an important pro-vitamin A source, which is essential for maintaining a healthy vision and cognitive processes. OBJECTIVE: This work reviews the current knowledge about the chemistry and biological activities of carotenoids in red mamey. METHOD: An exhaustive extraction is the most usual methodology to isolate and thoroughly characterize the carotenoids present in this fruit. High performance liquid chromatography is used to determine the profile of total carotenoids and its purity, while atmospheric pressure chemical ionization was used to determine their molecular weight and nuclear magnetic resonance determined their structure. RESULT: For each 100 g of fresh weight, 0.12 mg of total carotenoid from this fruit can be obtained. Out of the more than 47 reported carotenoids in red mamey, only 34 have a detailed characterization. CONCLUSION: It is important to continue studying the chemical composition and biological activity of this unique tropical fruit with commercial and nutritional value.

Optimal governance and implementation of vaccination programmes to contain the COVID-19 pandemic.

Since the recent introduction of several viable vaccines for SARS-CoV-2, vaccination uptake has become the key factor that will determine our success in containing the COVID-19 pandemic. We argue that game theory and social network models should be used to guide decisions pertaining to vaccination programmes for the best possible results. In the months following the introduction of vaccines, their availability and the human resources needed to run the vaccination programmes have been scarce in many countries. Vaccine hesitancy is also being encountered from some sections of the general public. We emphasize that decision-making under uncertainty and imperfect information, and with only conditionally optimal outcomes, is a unique forte of established game-theoretic modelling. Therefore, we can use this approach to obtain the best framework for modelling and simulating vaccination prioritization and uptake that will be readily available to inform important policy decisions for the optimal control of the COVID-19 pandemic.