In wastewater treatment plants (WWTPs), complex microbial communities process diverse chemical compounds from sewage. Secreted proteins are critical because many are the first to interact with or degrade external (macro)molecules. To better understand microbial functions in WWTPs, we predicted secreted proteomes of WWTP microbiota from more than 1,000 high-quality metagenome-assembled genomes (MAGs) from 23 Danish WWTPs with biological nutrient removal. Focus was placed on examining secreted catabolic exoenzymes that target major classes of macromolecules. We demonstrate that Bacteroidota has a high potential to digest complex polysaccharides, but also proteins and nucleic acids. Poorly understood activated sludge members of Acidobacteriota and Gemmatimonadota also have high capacities for extracellular polysaccharide digestion. Secreted nucleases are encoded by 61% of MAGs indicating an importance for extracellular DNA and/or RNA digestion in WWTPs. Secreted lipases were the least common macromolecule-targeting enzymes predicted, encoded mainly by Gammaproteobacteria and Myxococcota. In contrast, diverse taxa encode extracellular peptidases, indicating that proteins are widely used nutrients. Diverse secreted multi-heme cytochromes suggest capabilities for extracellular electron transfer by various taxa, including some Bacteroidota that encode undescribed cytochromes with >100 heme-binding motifs. Myxococcota have exceptionally large secreted protein complements, probably related to predatory lifestyles and/or complex cell cycles. Many Gammaproteobacteria MAGs (mostly former Betaproteobacteria) encode few or no secreted hydrolases, but many periplasmic substrate-binding proteins and ABC- and TRAP-transporters, suggesting they are mostly sustained by small molecules. Together, this study provides a comprehensive overview of how WWTPs microorganisms interact with the environment, providing new insights into their functioning and niche partitioning.IMPORTANCEWastewater treatment plants (WWTPs) are critical biotechnological systems that clean wastewater, allowing the water to reenter the environment and limit eutrophication and pollution. They are also increasingly important for the recovery of resources. They function primarily by the activity of microorganisms, which act as a \"living sponge,\" taking up and transforming nutrients, organic material, and pollutants. Despite much research, many microorganisms in WWTPs are uncultivated and poorly characterized, limiting our understanding of their functioning. Here, we analyzed a large collection of high-quality metagenome-assembled genomes from WWTPs for encoded secreted enzymes and proteins, with special emphasis on those used to degrade organic material. This analysis showed highly distinct secreted proteome profiles among different major phylogenetic groups of microorganisms, thereby providing new insights into how different groups function and co-exist in activated sludge. This knowledge will contribute to a better understanding of how to efficiently manage and exploit WWTP microbiomes.

Wound healing is an intricate multifactorial process that may alter the extent of scarring left by the wound. A substantial portion of the global population is impacted by non-healing wounds, imposing significant financial burdens on the healthcare system. The conventional dosage forms fail to improve the condition, especially in the presence of other morbidities. Thus, there is a pressing requirement for a type of wound dressing that can safeguard the wound site and facilitate skin regeneration, ultimately expediting the healing process. In this context, Chondroitin sulfate (CS), a sulfated glycosaminoglycan material, is capable of hydrating tissues and further promoting the healing. Thus, this comprehensive review article delves into the recent advancement of CS-based hydrogel/scaffolds for wound healing management. The article initially summarizes the various physicochemical characteristics and sources of CS, followed by a brief understanding of the importance of hydrogel and CS in tissue regeneration processes. This is the first instance of such a comprehensive summarization of CS-based hydrogel/scaffolds in wound healing, focusing more on the mechanistic wound healing process, furnishing the recent innovations and toxicity profile. This contemporary review provides a profound acquaintance of strategies for contemporary challenges and future direction in CS-based hydrogel/scaffolds for wound healing.

Biosensors function as sophisticated devices, converting biochemical reactions into electrical signals. Contemporary emphasis on developing biosensor devices with refined sensitivity and selectivity is critical due to their extensive functional capabilities. However, a significant challenge lies in the binding affinity of biosensors to biomolecules, requiring adept conversion and amplification of interactions into various signal modalities like electrical, optical, gravimetric, and electrochemical outputs. Overcoming challenges associated with sensitivity, detection limits, response time, reproducibility, and stability is essential for efficient biosensor creation. The central aspect of the fabrication of any biosensor is focused towards forming an effective interface between the analyte electrode which significantly influences the overall biosensor quality. Polymers and macromolecular systems are favored for their distinct properties and versatile applications. Enhancing the properties and conductivity of these systems can be achieved through incorporating nanoparticles or carbonaceous moieties. Hybrid composite materials, possessing a unique combination of attributes like advanced sensitivity, selectivity, thermal stability, mechanical flexibility, biocompatibility, and tunable electrical properties, emerge as promising candidates for biosensor applications. In addition, this approach enhances the electrochemical response, signal amplification, and stability of fabricated biosensors, contributing to their effectiveness. This review predominantly explores recent advancements in utilizing macrocyclic and macromolecular conjugated systems, such as phthalocyanines, porphyrins, polymers, etc. and their hybrids, with a specific focus on signal amplification in biosensors. It comprehensively covers synthetic strategies, properties, working mechanisms, and the potential of these systems for detecting biomolecules like glucose, hydrogen peroxide, uric acid, ascorbic acid, dopamine, cholesterol, amino acids, and cancer cells. Furthermore, this review delves into the progress made, elucidating the mechanisms responsible for signal amplification. The Conclusion addresses the challenges and future directions of macromolecule-based hybrids in biosensor applications, providing a concise overview of this evolving field. The narrative emphasizes the importance of biosensor technology advancement, illustrating the role of smart design and material enhancement in improving performance across various domains.

X-ray crystallography is an established tool to probe the structure of macromolecules with atomic resolution. Compared with alternative techniques such as single-particle cryo-electron microscopy and micro-electron diffraction, X-ray crystallography is uniquely suited to room-temperature studies and for obtaining a detailed picture of macromolecules subjected to an external electric field (EEF). The impact of an EEF on proteins has been extensively explored through single-crystal X-ray crystallography, which works well with larger high-quality protein crystals. This article introduces a novel design for a 3D-printed in situ crystallization plate that serves a dual purpose: fostering crystal growth and allowing the concurrent examination of the effects of an EEF on crystals of varying sizes. The plate\'s compatibility with established X-ray crystallography techniques is evaluated.

We evaluated whether thymol (THY) (30 mg/kg b.wt) could relieve the adverse effects of the neonicotinoid insecticide imidacloprid (IMD) (22.5 mg/kg b.wt) on the liver in a 56-day oral experiment and the probable underlying mechanisms. THY significantly suppressed the IMD-associated increase in hepatic enzyme leakage. Besides, the IMD-induced dyslipidemia was considerably corrected by THY. Moreover, THY significantly repressed the IMD-induced hepatic oxidative stress, lipid peroxidation, DNA damage, and inflammation. Of note, the Feulgen, mercuric bromophenol blue, and PAS-stained hepatic tissue sections analysis declared that treatment with THY largely rescued the IMD-induced depletion of the DNA, total proteins, and polysaccharides. Moreover, THY treatment did not affect the NF-kB p65 immunoexpression but markedly downregulated the Caspase-3 in the hepatocytes of the THY+IMD-treated group than the IMD-treated group. Conclusively, THY could efficiently protect against IMD-induced hepatotoxicity, probably through protecting cellular macromolecules and antioxidant, antiapoptotic, and anti-inflammatory activities.

OBJECTIVE: 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.

Hydraulic fracturing is vital in recovering hydrocarbons from oil and gas reservoirs. It involves injecting a fluid under high pressure into reservoir rock. A significant part of fracturing fluids is the addition of polymers that become gels or gel-like under reservoir conditions. Polymers are employed as viscosifiers and friction reducers to provide proppants in fracturing fluids as a transport medium. There are numerous systems for fracturing fluids based on macromolecules. The employment of natural and man-made linear polymers, and also, to a lesser extent, synthetic hyperbranched polymers, as additives in fracturing fluids in the past one to two decades has shown great promise in enhancing the stability of fracturing fluids under various challenging reservoir conditions. Modern innovations demonstrate the importance of developing chemical structures and properties to improve performance. Key challenges include maintaining viscosity under reservoir conditions and achieving suitable shear-thinning behavior. The physical architecture of macromolecules and novel crosslinking processes are essential in addressing these issues. The effect of macromolecule interactions on reservoir conditions is very critical in regard to efficient fluid qualities and successful fracturing operations. In future, there is the potential for ongoing studies to produce specialized macromolecular solutions for increased efficiency and sustainability in oil and gas applications.

Oral devices, such as foil-type devices, show great potential for the delivery of poorly permeable macromolecules by enabling unidirectional release of the loaded pharmaceutical composition in close proximity to the epithelium in the small intestine or colon. However, one of the primary concerns associated with the use of foil-type devices so far has been the utilization of nonbiodegradable elastomers in the fabrication of the devices. Therefore, research into biodegradable substitute materials with similar characteristics enables drug delivery in a sustainable and environmentally friendly manner. In this study, a biodegradable elastomer, polyoctanediol citrate (POC), was synthesized via a one-pot reaction, with subsequent purification and microscale pattern replication via casting. The microstructure geometry was designed to enable fabrication of foil-type devices with the selected elastomer, which has a high intrinsic surface free energy. The final elastomer was demonstrated to have an elastic modulus ranging up to 2.2 ± 0.1 MPa, with strain at failure up to 110.1 ± 1.5%. Devices were loaded with acetaminophen and enterically coated, demonstrating 100% release at 2.5 h, following dissolution for 1 h in 0.1 M hydrochloric acid and 1.5 h in pH 6.8 phosphate-buffered saline. The elastomer demonstrated promising properties based on mechanical testing, surface free energy evaluation, and degradation studies.

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.

OBJECTIVE: 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.