Programmable macromolecule-based RNA-targeting therapies to treat human neurological disorders.

Disruptions in RNA processing play critical roles in the pathogenesis of neurological diseases. In this Perspective, we discuss recent progress in the development of RNA-targeting therapeutic modalities. We focus on progress, limitations, and opportunities in a new generation of therapies engineered from RNA binding proteins and other endogenous RNA regulatory macromolecules to treat human neurological disorders.

Structural Determinants of Stimuli-Responsiveness in Amphiphilic Macromolecular Nano-assemblies.

Stimuli-responsive nano-assemblies from amphiphilic macromolecules could undergo controlled structural transformations and generate diverse macroscopic phenomenon under stimuli. Due to the controllable responsiveness, they have been applied for broad material and biomedical applications, such as biologics delivery, sensing, imaging, and catalysis. Understanding the mechanisms of the assembly-disassembly processes and structural determinants behind the responsive properties is fundamentally important for designing the next generation of nano-assemblies with programmable responsiveness. In this review, we focus on structural determinants of assemblies from amphiphilic macromolecules and their macromolecular level alterations under stimuli, such as the disruption of hydrophilic-lipophilic balance (HLB), depolymerization, decrosslinking, and changes of molecular packing in assemblies, which eventually lead to a series of macroscopic phenomenon for practical purposes. Applications of stimuli-responsive nano-assemblies in delivery, sensing and imaging were also summarized based on their structural features. We expect this review could provide readers an overview of the structural considerations in the design and applications of nanoassemblies and incentivize more explorations in stimuli-responsive soft matters.

Chemo-Enzymatic Derivatization of Glycerol-Based Oligomers: Structural Elucidation and Potential Applications.

Switching from oil-based to bio-based feedstocks to ensure the green transition to a sustainable and circular future is one of the most pressing challenges faced by many industries worldwide. For the cosmetics and personal and house care industries there is a strong drive to accelerate this transition from the customers that starts favoring the purchase of naturally derived and bio-degradable products over the traditionally available products. In this work we developed a series of fully biobased macromolecules constituted of a glycerol-based oligoester backbone. Based on the subsequent derivatization with fatty acids or peptides, the resulting products may find application as emulsifiers, wetting agents, and potential vectors for the delivery of bioactive peptides. All steps of the resulting macromolecules were conducted following the green chemistry principles with no toxic or environmentally damaging compounds that were used in the overall production process.

GABA-edited MEGA-PRESS at 3 T: Does a measured macromolecule background improve linear combination modeling?

PURPOSE: The J-difference edited γ-aminobutyric acid (GABA) signal is contaminated by other co-edited signals-the largest of which originates from co-edited macromolecules (MMs)-and is consequently often reported as "GABA+." MM signals are broader and less well-characterized than the metabolites, and are commonly approximated using a Gaussian model parameterization. Experimentally measured MM signals are a consensus-recommended alternative to parameterized modeling; however, they are relatively under-studied in the context of edited MRS. METHODS: To address this limitation in the literature, we have acquired GABA-edited MEGA-PRESS data with pre-inversion to null metabolite signals in 13 healthy controls. An experimental MM basis function was derived from the mean across subjects. We further derived a new parameterization of the MM signals from the experimental data, using multiple Gaussians to accurately represent their observed asymmetry. The previous single-Gaussian parameterization, mean experimental MM spectrum and new multi-Gaussian parameterization were compared in a three-way analysis of a public MEGA-PRESS dataset of 61 healthy participants. RESULTS: Both the experimental MMs and the multi-Gaussian parameterization exhibited reduced fit residuals compared to the single-Gaussian approach (p = 0.034 and p = 0.031, respectively), suggesting they better represent the underlying data than the single-Gaussian parameterization. Furthermore, both experimentally derived models estimated larger MM fractional contribution to the GABA+ signal for the experimental MMs (58%) and multi-Gaussian parameterization (58%), compared to the single-Gaussian approach (50%). CONCLUSIONS: Our results indicate that single-Gaussian parameterization of edited MM signals is insufficient and that both experimentally derived GABA+ spectra and their parameterized replicas improve the modeling of GABA+ spectra.

Fast magnetization transfer saturation imaging of the brain using MP2RAGE T1 mapping.

PURPOSE: Magnetization transfer saturation (MTsat) mapping is commonly used to examine the macromolecular content of brain tissue. This study compared variable flip angle (VFA) T1 mapping against compressed-sensing MP2RAGE (csMP2RAGE) T1 mapping for accelerating MTsat imaging. METHODS: VFA, MP2RAGE, and csMP2RAGE were compared against inversion-recovery T1 in an aqueous phantom at 3 T. The same 1-mm VFA, MP2RAGE, and csMP2RAGE protocols were acquired in 4 healthy subjects to compare T1 and MTsat. Bloch-McConnell simulations were used to investigate differences between the phantom and in vivo T1 results. Ten healthy controls were imaged twice with the csMP2RAGE MTsat protocol to quantify repeatability. RESULTS: The MP2RAGE and csMP2RAGE protocols were 13.7% and 32.4% faster than the VFA protocol, respectively. At these scan times, all approaches provided strong repeatability and accurate T1 times (< 5% difference) in the phantom, but T1 accuracy was more impacted by T2 for VFA than for MP2RAGE. In vivo, VFA estimated longer T1 times than MP2RAGE and csMP2RAGE. Simulations suggest that the differences in the T1 measured using VFA, MP2RAGE, and inversion recovery could be explained by the magnetization-transfer effects. In the test-retest experiment, we found that the csMP2RAGE has a minimum detectable change of 2.3% for T1 mapping and 7.8% for MTsat imaging. CONCLUSIONS: We demonstrated that MP2RAGE can be used in place of VFA T1 mapping in an MTsat protocol. Furthermore, a shorter scan time and high repeatability can be achieved using the csMP2RAGE sequence.

Age-related differences in macromolecular resonances observed in ultra-short-TE STEAM MR spectra at 7T.

PURPOSE: To understand how macromolecular content varies in the human brain with age in a large cohort of healthy subjects. METHODS: In-vivo 1H-MR spectra were acquired using ultra-short TE STEAM at 7T in the posterior cingulate cortex. Macromolecular content was studied in 147 datasets from a cohort ranging in age from 19 to 89 y. Three fitting approaches were used to evaluate the macromolecular content: (1) a macromolecular resonances model developed for this study; (2) LCModel-simulated macromolecules; and (3) a combination of measured and LCModel-simulated macromolecules. The effect of age on the macromolecular content was investigated by considering age both as a continuous variable (i.e., linear regressions) and as a categorical variable (i.e., multiple comparisons among sub-groups obtained by stratifying data according to age by decade). RESULTS: While weak age-related effects were observed for macromolecular peaks at ˜0.9 (MM09), ˜1.2 (MM12), and ˜1.4 (MM14) ppm, moderate to strong effects were observed for peaks at ˜1.7 (MM17), and ˜2.0 (MM20) ppm. Significantly higher MM17 and MM20 content started from 30 to 40 y of age, while for MM09, MM12, and MM14, significantly higher content started from 60 to 70 y of age. CONCLUSIONS: Our findings provide insights into age-related differences in macromolecular contents and strengthen the necessity of using age-matched measured macromolecules during quantification.

Metabolite T1 relaxation times decrease across the adult lifespan.

Relaxation correction is an integral step in quantifying brain metabolite concentrations measured by in vivo magnetic resonance spectroscopy (MRS). While most quantification routines assume constant T1 relaxation across age, it is possible that aging alters T1 relaxation rates, as is seen for T2 relaxation. Here, we investigate the age dependence of metabolite T1 relaxation times at 3 T in both gray- and white-matter-rich voxels using publicly available metabolite and metabolite-nulled (single inversion recovery TI = 600 ms) spectra acquired at 3 T using Point RESolved Spectroscopy (PRESS) localization. Data were acquired from voxels in the posterior cingulate cortex (PCC) and centrum semiovale (CSO) in 102 healthy volunteers across 5 decades of life (aged 20-69 years). All spectra were analyzed in Osprey v.2.4.0. To estimate T1 relaxation times for total N-acetyl aspartate at 2.0 ppm (tNAA2.0) and total creatine at 3.0 ppm (tCr3.0), the ratio of modeled metabolite residual amplitudes in the metabolite-nulled spectrum to the full metabolite signal was calculated using the single-inversion-recovery signal equation. Correlations between T1 and subject age were evaluated. Spearman correlations revealed that estimated T1 relaxation times of tNAA2.0 (rs = -0.27; p < 0.006) and tCr3.0 (rs = -0.40; p < 0.001) decreased significantly with age in white-matter-rich CSO, and less steeply for tNAA2.0 (rs = -0.228; p = 0.005) and (not significantly for) tCr3.0 (rs = -0.13; p = 0.196) in graymatter-rich PCC. The analysis harnessed a large publicly available cross-sectional dataset to test an important hypothesis, that metabolite T1 relaxation times change with age. This preliminary study stresses the importance of further work to measure age-normed metabolite T1 relaxation times for accurate quantification of metabolite levels in studies of aging.

Self-immolation Assisted Morphology Transformation of Prebiotic Lipidated-cationic Amino Acids: Electro-droplet Mediated C-C Coupling Reaction to Synthesize Macromolecules.

Compartmentalization protected biomolecules from the fluctuating environments of early Earth. Although contemporary cells mostly use phospholipid-based bilayer membranes, the utility of non-bilayer compartments was not ruled out during the prebiotic and modern eras. In the present study, we demonstrated the prebiotic synthesis of lipidated cationic amino acid-based amphiphiles [lauryl ester of lysine (LysL); ornithine (OrnL); and 2,4-diamino butyric acid (DabL)] using model dry-down reaction. These amphiphiles self-assemble into micellar membranes. However, the OrnL and DabL-based micelles undergo pH-responsive transformation to lipid droplet-like morphologies, a modelcompartment in the prebiotic Earth. These cationic droplets encapsulated prebiotic molecules (isoprene) and assisted electron transfer reaction to synthesize isoprenoid derivatives at primitive Earth conditions. The self-assembly of prebiotic amphiphiles, their transformation to droplet compartments, and droplet-assisted C-C bond formation reaction might have helped the evolution to synthesize various biomolecules required for the origin of life.

Negligible In Vitro Recovery of Macromolecules from Microdialysis Using 100 kDa Probes and Dextran in Perfusion Fluid.

Microdialysis is applied in neurointensive care to monitor cerebral glucose metabolism. If recoverable, macromolecules may also serve as biomarkers in brain disease and provide clues to their passage across the blood-brain barrier. Our study aimed to investigate the in vitro recovery of human micro- and macromolecules using microdialysis catheters and perfusion fluids approved for clinical use. In vitro microdialysis of a bulk solution containing physiological or supraphysiological concentrations of glucose, lactate, pyruvate, human IgG, serum albumin, and hemoglobin was performed using two different catheters and perfusion fluids. One had a membrane cut-off of 20 kDa and was used with a standard CNS perfusion fluid, and the other had a membrane cut-off of 100 kDa and was perfused with the same solution supplemented with dextran. The flow rate was 0.3 µl/min. We used both push and push-pull methods. Dialysate samples were collected at 2-h intervals for 6 h and analyzed for relative recovery of each substance. The mean relative recovery of glucose, pyruvate, and lactate was > 90% in all but two sets of experiments. In contrast, the relative recovery of human IgG, serum albumin, and hemoglobin from both bulk solutions was below the lower limit of quantification (LLOQ). Using a push-pull method, recovery of human IgG, serum albumin, and hemoglobin from a bulk solution with supraphysiological concentrations were above LLOQ but with low relative recovery (range 0.9%-1.6%). In summary, exchanging the microdialysis setup from a 20 kDa catheter with a standard perfusion fluid for a 100 kDa catheter with a perfusion solution containing dextran did not affect the relative recovery of glucose and its metabolites. However, it did not result in any useful recovery of the investigated macromolecules at physiological levels, either with or without a push-pull pump system.

Therapeutic Ultrasound for Enhanced Corneal Permeability to Macromolecules.

OBJECTIVES: Topically applied macromolecules have the potential to provide vision-saving treatments for many of the leading causes of blindness in the United States. The aim of this study was to determine if ultrasound can be applied to increase transcorneal drug delivery of macromolecules without dangerously overheating surrounding ocular tissues. METHODS: Dissected corneas of adult rabbits were placed in a diffusion cell between a donor compartment filled with a solution of macromolecules (40, 70 kDa, or 150 kDa) and a receiver compartment. Each cornea was exposed to the drug solution for 60 minutes, with the experimental group receiving 5 minutes of continuous ultrasound or 10 minutes of pulsed ultrasound at a 50% duty cycle (pulse repetition frequency of 500 ms on, 500 ms off) at the beginning of treatment. Unfocused circular ultrasound transducers were operated at 0.5 to 1 W/cm2 intensity and at 600 kHz frequency. RESULTS: The greatest increase in transcorneal drug delivery seen was 1.2 times (P < .05) with the application of pulsed ultrasound at 0.5 W/cm2 and 600 kHz for 10 minutes with 40 kDa macromolecules. Histological analysis revealed structural damage mostly in the corneal epithelium, with most damage occurring at the epithelial surface. CONCLUSIONS: This study suggests that ultrasound may be used for enhancing transcorneal delivery of macromolecules of lower molecular weights. Further research is needed on the long-term effects of ultrasound parameters used in this study on human ocular tissues.

Effects of Alkaline Extraction pH on Amino Acid Compositions, Protein Secondary Structures, Thermal Stability, and Functionalities of Brewer's Spent Grain Proteins.

A high alkaline pH was previously demonstrated to enhance the extraction yield of brewer's spent grains (BSG) proteins. The effects of extraction pH beyond the extraction yield, however, has not been investigated before. The present work examined the effects of extraction pH (pH 8-12) on BSG proteins' (1) amino acid compositions, (2) secondary structures, (3) thermal stability, and (4) functionalities (i.e., water/oil holding capacity, emulsifying, and foaming properties). The ideal extraction temperature (60 °C) and BSG-to-solvent ratio (1:20 w/v) for maximizing the extraction yield were first determined to set the conditions for the pH effect study. The results showed that a higher extraction pH led to more balanced compositions between hydrophilic and hydrophobic amino acids and higher proportions of random coils structures indicating increased protein unfolding. This led to superior emulsifying properties of the extracted proteins with more than twofold improvement between pH 8 and a pH larger than 10. The extraction pH, nevertheless, had minimal impact on the water/oil holding capacity, foaming properties, and thermal denaturation propensity of the proteins. The present work demonstrated that a high alkaline pH at pH 11-12 was indeed ideal for both maximizing the extraction yield (37-46 wt.%) and proteins' functionalities.

Synthesis and Morphology Characteristics of New Highly Branched Polycaprolactone PCL.

A simple and efficient method for the synthesis of biodegradable, highly branched polycaprolactone (PCL) is presented. The solvent-free (bulk) reaction was carried out via ring opening polymerization (ROP), catalyzed by tin octanoate Sn(Oct)2, and it employed hyperbranched polyamide (HPPA) as a macro-initiator. The core-shell structure of the obtained products (PCL-HPPA), with the hyperbranched HPPA core and linear PCL chains as shell, was in the focus of the product characterization. 1H nuclear magnetic resonance (1H NMR) and elemental analysis confirmed the covalent incorporation of the HPPA in the products, as well as a high degree of grafting conversion of its amino functional groups. Confocal Raman Micro spectroscopy, and especially Time-of-Flight Secondary Ion Mass Spectrometry, further supported the existence of a core-shell structure in the products. Direct observation of macromolecules by means of cryogenic transmission electron microscopy, as well as gel permeation chromatography (GPC), suggested the existence of a minor 'aggregated' product fraction with multiple HPPA cores, which was attributed to transesterification reactions. Differential scanning calorimetry, as well as X-ray diffraction, demonstrated that the PCL-HPPA polymers displayed a similar degree of crystallinity to linear neat PCL, but that the branched products possessed smaller and less regular crystallites.

Looking for a Novel Vegan Protein Supplement from Faba Bean, Lupine, and Soybean: a Dietary and Industrial Standpoint.

Global population growth poses a threat to sustainable development. Meanwhile, the use of plant proteins as healthy and sustainable alternatives to animal proteins needs further research. Therefore, this investigation was designed to study the nutritive, structural, and thermal properties of isolated protein fractions from different legumes, i.e., faba bean (FPI), soybean (SPI), and lupine (LPI). As a prospective plant-based protein powder, an equal mixture (MPI) of the three prior legume samples was formulated to study its properties compared to each sole sample. The alkaline extraction and isoelectric precipitation (AE-IP) technique was used for protein isolation. Results showed that all protein isolates had reasonable levels of protein with maximum protein content in SPI (96.15%). The MPI sample, however, came out on top in terms of amino acid profile followed by FBI. Compared to SPI and LPI, it had the highest isoleucine content and higher methionine, valine, leucine, phenylalanine, and lysine. Moreover, MPI showed a median particle charge (-37.1 mV) compared to FPI, SPI, and LPI samples. MPI sample peak showed resistance to heat denaturation at a temperature greater than 200 °C when the DSC test was conducted. With respect to its rheological characteristics, it outperformed the other three protein isolates and exhibited the highest values of storage modulus G' and loss modulus G". Consequently, our study suggests that pulse-derived protein isolate mixture can be used as a unique type of nutritious dietary protein supplement. It could be a good nutritional alternative to proteins derived from animals.

Development of Stable Water-Soluble Supratomic Silver Clusters Utilizing A Polyoxoniobate-Protected Strategy: Giant Core-Shell-Type Ag8@Nb162 Fluorescent Nanocluster.

Atomically precise low-nuclearity (n<10) silver nanoclusters (AgNCs) have garnered significant interest due to their size-dependent optical properties and diverse applications. However, their synthesis has remained challenging, primarily due to their inherent instability. The present study introduces a new feasible approach for clustering silver ions utilizing highly negative and redox-inert polyoxoniobates (PONbs) as all-inorganic ligands. This strategy not only enables the creation of novel Ag-PONb composite nanoclusters but also facilitates the synthesis of stable low-nuclearity AgNCs. Using this method, we have successfully synthesized a small octanuclear rhombic [Ag8]6+ AgNC stabilized by six highly negative [LiNb27O75]14- polyoxoanions. This marks the first PONb-protected superatomic AgNC, designated as {Ag8@(LiNb27O75)6} (Ag8@Nb162), with an aesthetically spherical core-shell structure. The crystalline Ag8@Nb162 is stable under ambient conditions, What's more, it is water-soluble and able to maintain its molecular cluster structure intact in water. Further, the stable small [Ag8]6+ AgNC has interesting temperature- and pH-dependent reversible fluorescence response, based on which a multiple optical encryption mode for anti-counterfeit technology was demonstrated. This work offers a promising avenue for the synthesis of fascinating and stable PONb-protected AgNCs and sheds light on the development of new-type optical functional materials.

Organophosphorus Compound Formation Through the Oxidation of Reduced Oxidation State Phosphorus Compounds on the Hadean Earth.

Reduced oxidation state phosphorus compounds may have been brought to the early Earth via meteorites or could have formed through geologic processes. These compounds could have played a role in the origin of biological phosphorus (P, hereafter) compounds. Reduced oxidation state P compounds are generally more soluble in water and are more reactive than orthophosphate and its associated minerals. However, to date no facile routes to generate C-O-P type compounds using reduced oxidation state P compounds have been reported under prebiotic conditions. In this study, we investigate the reactions between reduced oxidation state P compounds-and their oxidized products generated via Fenton reactions-with the nucleosides uridine and adenosine. The inorganic P compounds generated via Fenton chemistry readily react with nucleosides to produce organophosphites and organophosphates, including phosphate diesters via one-pot syntheses. The reactions were facilitated by NH4+ ions and urea as a condensation agent. We also present the results of the plausible stability of the organic compounds such as adenosine in an environment containing an abundance of H2O2. Such results have direct implications on finding organic compounds in Martian environments and other rocky planets (including early Earth) that were richer in H2O2 than O2. Finally, we also suggest a route for the sink of these inorganic P compounds, as a part of a plausible natural P cycle and show the possible formation of secondary phosphate minerals such as struvite and brushite on the early Earth.

Macromolecules Promoting Robust Zinc Anode by Synergistic Coordination Effect and Charge Redistribution.

Zn dendrite formation is the main obstacle to commercializing aqueous zinc-ion batteries (ZIBs). α-cyclodextrin (α-CD) is proposed as an environmentally friendly macromolecule additive in the ZnSO4 -based electrolyte to obtain stable and reversible Zn anodes. The results show that α-CD molecules' unique 3D structure can effectively regulate the mass transfer of the electrolyte components and isolate the Zn anode from H2 O molecules. The α-CD provides abundant electrons to the Zn (002) crystallographic plane, which induces charge density redistribution. Such an effect relieves the reduction and aggregation of Zn2+ cations while protecting the Zn metal anode from water molecules. Finally, a small amount of α-CD additive (0.01 M) can enhance the performance of Zn significantly in Zn||Cu cells (1980 cycles with 99.45% average CE) and Zn||Zn cells (8000 h ultra-long cycle life). The excellent practical applicability was further verified in Zn||MnO2 cells.

BioSAXS at European Synchrotron Radiation Facility - Extremely Brilliant Source: BM29 with an upgraded source, detector, robot, sample environment, data collection and analysis software.

As part of its Extremely Brilliant Source (EBS) upgrade project, the ESRF's BM29 BioSAXS beamline was subject to a significant upgrade and refurbishment. In addition to the replacement of the beamline's original bending magnet source by a two-pole wiggler, leading to an increase in brilliance by a factor of 60, the sample environment of the beamline was almost completely refurbished: a vacuum-compatible Pilatus3 X 2M with a sensitive area of 253.7 mm × 288 mm and frame rates up to 250 Hz was installed, increasing the active area available and thus the q-scaling of scattering images taken; the sample changer was replaced with an upgraded version, allowing more space for customizable sample environments and the installation of two new sample exposure units; the software associated with the beamline was also renewed. In addition, the layout and functionality of the BSXCuBE3 (BioSAXS Customized Beamline Environment) data acquisition software was redesigned, providing an intuitive `user first' approach for inexperienced users, while at the same time maintaining more powerful options for experienced users and beamline staff. Additional features of BSXCuBE3 are queuing of samples; either consecutive sample changer and/or SEC-SAXS (size-exclusion chromatography small-angle X-ray scattering) experiments, including column equilibration were also implemented. Automatic data processing and analysis are now managed via Dahu, an online server with upstream data reduction, data scaling and azimuthal integration built around PyFAI (Python Fast Azimuthal Integration), and data analysis performed using the open source FreeSAS. The results of this automated data analysis pipeline are displayed in ISPyB/ExiSAXS. The upgraded BM29 has been in operation since the post-EBS restart in September 2020, and here a full description of its new hardware and software characteristics together with examples of data obtained are provided.

Feasibility and implications of using subject-specific macromolecular spectra to model short echo time magnetic resonance spectroscopy data.

Expert consensus recommends linear-combination modeling (LCM) of 1 H MR spectra with sequence-specific simulated metabolite basis function and experimentally derived macromolecular (MM) basis functions. Measured MM basis functions are usually derived from metabolite-nulled spectra averaged across a small cohort. The use of subject-specific instead of cohort-averaged measured MM basis functions has not been studied widely. Furthermore, measured MM basis functions are not widely available to non-expert users, who commonly rely on parameterized MM signals internally simulated by LCM software. To investigate the impact of the choice of MM modeling, this study, therefore, compares metabolite level estimates between different MM modeling strategies (cohort-mean measured; subject-specific measured; parameterized) in a lifespan cohort and characterizes its impact on metabolite-age associations. 100 conventional (TE = 30 ms) and metabolite-nulled (TI = 650 ms) PRESS datasets, acquired from the medial parietal lobe in a lifespan cohort (20-70 years of age), were analyzed in Osprey. Short-TE spectra were modeled in Osprey using six different strategies to consider the MM baseline. Fully tissue- and relaxation-corrected metabolite levels were compared between MM strategies. Model performance was evaluated by model residuals, the Akaike information criterion (AIC), and the impact on metabolite-age associations. The choice of MM strategy had a significant impact on the mean metabolite level estimates and no major impact on variance. Correlation analysis revealed moderate-to-strong agreement between different MM strategies (r > 0.6). The lowest relative model residuals and AIC values were found for the cohort-mean measured MM. Metabolite-age associations were consistently found for two major singlet signals (total creatine (tCr])and total choline (tCho)) for all MM strategies; however, findings for metabolites that are less distinguishable from the background signals associations depended on the MM strategy. A variance partition analysis indicated that up to 44% of the total variance was related to the choice of MM strategy. Additionally, the variance partition analysis reproduced the metabolite-age association for tCr and tCho found in the simpler correlation analysis. In summary, the inclusion of a single high signal-to-noise ratio MM basis function (cohort-mean) in the short-TE LCM leads to more lower model residuals and AIC values compared with MM strategies with more degrees of freedom (Gaussian parametrization) or subject-specific MM information. Integration of multiple LCM analyses into a single statistical model potentially allows to identify the robustness in the detection of underlying effects (e.g., metabolite vs. age), reduces algorithm-based bias, and estimates algorithm-related variance.

Flavor profile and role of macromolecules in the flavor generation of shrimp meat and valorization of shrimp by-products as a source of flavor compounds: a review.

Shrimps are a widely cultivated species among crustaceans worldwide due to their nutritional profile and delicacy. Because of their unique flavor, shrimp-based food products are gaining consumer demand, so there is a need to understand the flavor chemistry of shrimp meat. Further, the processing and macromolecules of shrimp meat play a significant role in flavor generation and suggest a focus on their research. However, shrimp processing generates a large amount of solid and liquid waste, creating disposal problems and environmental hazards. To overcome this, utilizing these waste products, a rich source of valuable flavor compounds is necessary. This review comprehensively discusses the nutritional aspects, flavor profile, and role of macromolecules in the flavor generation of shrimp meat. Besides, recent trends in analyzing the aroma profile of shrimp and the benefits of shrimp by-products as a source of flavor compounds have been addressed. The delicious flavor of shrimp meat is due to its volatile and nonvolatile flavor compounds. Proteins play a major role in the textural and flavor adsorption properties of shrimp meat-based products. Green extraction technologies, especially ultrasonication, are recommended for valorizing shrimp by-products as a source of flavor compounds, which have enormous applications in the food and flavor industries.

Valorization of environmental-burden waste towards microalgal metabolites production.

The present study develops a novel concept of using waste media as an algal nutrient resource compared to the usual growth media with the aid of growth kinetics study and metabolite production abilities. Food- and agri-compost wastes are compact structures with elemental compounds for microbial media. As a part of the study, environ-burden wastes (3:1) as a food source for photosynthetic algae as a substitute for the costly nutrient media were proposed. The environment-burden waste was also envisaged for macromolecule production, i.e., 99200 µg/ml lipid, 112.5 µg/ml protein, and 8.75 µg/ml carbohydrate with different dilutions of agri-waste, bold basal media (BBM), and Food waste, respectively. The fabricated growth kinetics and dynamics showcased the unstructured models of different photosynthetic algal growth phases and the depiction of productivity and kinetic parameters. The theoretical maximum biomass concentration (Xp) was found to be more (0.871) with diluted agricompost media than the usual BBM (0.697). The XLim values were found to be 0.362, 0.323 and 0.209 for BBM, diluted agri-compost media and diluted food waste media, respectively. Overall, the study proposes a cleaner approach of utilizing the wastes as growth media through a circular economy approach which eventually reduces the growth media cost with integrated macromolecule production capabilities.