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[Display omitted] Lipid-based lyotropic liquid crystalline nanoparticles (LCNPs) face stability challenges in biological fluids during clinical translation. Ionic Liquids (ILs) have emerged as effective solvent additives for tuning the structure of LCNP's and enhancing their stability. We investigated the effect of a library of 21 choline-based biocompatible ILs with 9 amino acid anions as well as 10 other organic/inorganic anions during the preparation of phytantriol (PHY)-based LCNPs, followed by incubation in human serum and serum proteins. Small angle X-ray scattering (SAXS) results show that the phase behaviour of the LCNPs depends on the IL concentration and anion structure. Incubation with human serum led to a phase transition from the inverse bicontinuous cubic (Q 2) to the inverse hexagonal (H 2) mesophase, influenced by the specific IL present. Liquid chromatography-mass spectrometry (LC-MS) and proteomics analysis of selected samples, including PHY control and those with choline glutamate, choline hexanoate, and choline geranate, identified abundant proteins in the protein corona, including albumin, apolipoproteins, and serotransferrin. The composition of the protein corona varied among samples, shedding light on the intricate interplay between ILs, internal structure and surface chemistry of LCNPs, and biological fluids. [ABSTRACT FROM AUTHOR]

Cholestatic liver disease is defined as the bile acids (BAs) accumulation in the liver caused by impaired synthesis, and secretion, together with excretion of BAs due to a variety of factors, which, if left untreated, can result in hepatic fibrosis, cholestatic cholangitis, cholestatic cirrhosis, eventually, end-stage liver disease. Currently, modulation of BA metabolism is still a prospective therapeutic strategy for treating the cholestatic diseases. Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor with far-reaching effects on the chronic liver disease. However, its role and mechanism in cholestatic liver damage is still unknown. Therefore, in this work, we explored the impact of AHR on the cholestatic liver injury using AHR overexpression mediated by adeno-associated viral (AAV) vectors. We found that AHR is differentially expressed in different stages of cholestatic liver disease, showing either down-regulation or an increase in protective effects. Overexpression of AHR increased body weight, decreased serum total bilirubin (TBil) and alkaline phosphatase (ALP), reduced porphyrin accumulation in liver tissue, and regulated the bile acid pool in the cholestatic mouse model induced by DDC diet. Overall, our data indicate that AHR attenuated cholestatic liver injury. AHR function indicates that it may have an action in the clinical management of cholestasis. • AHR attenuates initial weight loss by DDC intoxication. • AHR reduced the accumulation of porphyrin caused by the DDC diet. • AHR selectively reduces taurine-conjugated bile acid contents. [ABSTRACT FROM AUTHOR]

[Display omitted] Ions are important to modulate protein properties, including solubility and stability, through specific ion effects. Ionic liquids (ILs) are designer salts with versatile ion combinations with great potential to control protein properties. Although protein-ion binding of common metals is well-known, the IL effect on proteins is not well understood. Here, we employ the model protein lysozyme in dilute and concentrated IL solutions to determine the specific ion binding effect on protein phase behaviour, activity, size and conformational change, aggregation and intermolecular interactions. A combination of spectroscopic techniques, activity assays, small-angle X-ray scattering, and crystallography highlights that ILs, particularly their anions, bind to specific sites in the protein hydration layer via polar contacts on charged, polar and aromatic residues. The specific ion binding can induce more flexible loop regions in lysozyme, while the ion binding in the bulk phase can be more dynamic in solution. Overall, the protein behaviour in ILs depends on the net effect of nonspecific interactions and specific ion binding. Compared to formate, the nitrate anion induced high protein solubility, low activity, elongated shape and aggregation, which is largely owing to its higher propensity for ion binding. These findings provide new insights into protein-IL binding interactions and using ILs to modulate protein properties. [ABSTRACT FROM AUTHOR]

[Display omitted] Globular proteins are well-folded model proteins, where ions can substantially influence their structure and aggregation. Ionic liquids (ILs) are salts in the liquid state with versatile ion combinations. Understanding the IL effect on protein behavior remains a major challenge. Here, we employed small angle X-ray scattering to investigate the effect of aqueous ILs on the structure and aggregation of globular proteins, namely, hen egg white lysozyme (Lys), human lysozyme (HLys), myoglobin (Mb), β-lactoglobulin (βLg), trypsin (Tryp) and superfolder green fluorescent protein (sfGFP). The ILs contain ammonium-based cations paired with the mesylate, acetate or nitrate anion. Results showed that only Lys was monomeric, whereas the other proteins formed small or large aggregates in buffer. Solutions with over 17 mol% IL resulted in significant changes in the protein structure and aggregation. The Lys structure was expanded at 1 mol% but compact at 17 mol% with structural changes in loop regions. HLys formed small aggregates, with the IL effect similar to Lys. Mb and βLg mostly had distinct monomer and dimer distributions depending on IL type and IL concentration. Complex aggregation was noted for Tryp and sfGFP. While the anion had the largest ion effect, changing the cation also induced the structural expansion and protein aggregation. [ABSTRACT FROM AUTHOR]

Head and neck tumors (HNTs) constitute a multifaceted ensemble of pathologies that primarily involve regions such as the oral cavity, pharynx, and nasal cavity. The intricate anatomical structure of these regions poses considerable challenges to efficacious treatment strategies. Despite the availability of myriad treatment modalities, the overall therapeutic efficacy for HNTs continues to remain subdued. In recent years, the deployment of artificial intelligence (AI) in healthcare practices has garnered noteworthy attention. AI modalities, inclusive of machine learning (ML), neural networks (NNs), and deep learning (DL), when amalgamated into the holistic management of HNTs, promise to augment the precision, safety, and efficacy of treatment regimens. The integration of AI within HNT management is intricately intertwined with domains such as medical imaging, bioinformatics, and medical robotics. This article intends to scrutinize the cutting-edge advancements and prospective applications of AI in the realm of HNTs, elucidating AI's indispensable role in prevention, diagnosis, treatment, prognostication, research, and inter-sectoral integration. The overarching objective is to stimulate scholarly discourse and invigorate insights among medical practitioners and researchers to propel further exploration, thereby facilitating superior therapeutic alternatives for patients. [ABSTRACT FROM AUTHOR]

In this work, we study the long time behavior of a coupled PDEs' system consisting of one wave equation and one degenerate heat equation in two connected regions. The coupling between these two different components occurs at the interface with certain transmission conditions. For the system on rectangular domain, by frequency domain analysis, the explicit polynomial decay rate of the solutions to the system is obtained, which only depends on the degree of degeneration of the diffusion coefficient of the heat equation near the interface line. Specifically, a clear relationship between the decay rate and the degeneration parameter of the diffusion coefficient is identified. Moreover, the explicit decay rate of the solutions to such a system on one-dimensional domain is also further estimated. Especially, these two obtained decay rates are consistent with the optimal ones for the systems on rectangular domain and one-dimensional domain with constant-diffusion coefficient, obtained by Batty et al. [7] and Zhang and Zuazua [23] , respectively. From this view, the obtained decay rates can all be considered as sharp ones for such kind of degenerate systems. [ABSTRACT FROM AUTHOR]

[Display omitted] Ionic liquids (ILs) have been used in solvents for proteins in many applications, including biotechnology, pharmaceutics, and medicine due to their tunable physicochemical and biological properties. Protein aggregation is often undesirable, and predominantly occurs during bioprocesses, while the aggregation process can be reversible or irreversible and the aggregates formed can be native/non-native and soluble/insoluble. Recent studies have clearly identified key properties of ILs and IL-water mixtures related to protein performance, suggesting the use of the tailorable properties of ILs to inhibit protein aggregation, to promote protein crystallization, and to control protein aggregation pathways. This review discusses the critical properties of IL and IL-water mixtures and presents the latest understanding of the protein aggregation pathways and the development of IL systems that affect or control the protein aggregation process. Through this feature article, we hope to inspire further advances in understanding and new approaches to controlling protein behavior to optimize bioprocesses. [ABSTRACT FROM AUTHOR]

[Display omitted] Proteins generally tend to aggregate with less desirable properties in numerous solvents, which is one of the major challenges in the development of solvents for functional proteins. This work aims to utilize fluorescence spectroscopy and small angle X-ray scattering (SAXS) to understand the effects of ionic liquids (ILs) on the fluorescence and aggregation behavior of superfolder green fluorescent protein (sfGFP). The studied ILs consisted of four different anions coupled with primary, tertiary and quaternary ammonium cations. The results show that the chromophore fluorescence was generally maintained in 1 mol% IL-water mixtures, then decreased with increasing IL concentration. We primarily employed the pseudo-radius of gyration (pseudo-R g) to evaluate sfGFP aggregation. The sfGFP was less aggregated with nitrate-based ILs compared to in buffer, and more aggregated in the mesylate-based ILs. Further, we show that the polyol additives of glycerol and glucose in IL-water mixtures slightly decreased the sfGFP propensity to aggregate. Size-exclusion chromatography (SEC)-SAXS was used to characterize the monomeric sfGFP in ethylammonium nitrate (EAN) and triethylammonium mesylate (TEAMs)-water mixtures. The presence of 1 mol% TEAMs maintained the sfGFP fluorescence, promoted the compact structure, but slightly increased the amount of large aggregates, which contrasted with that of EAN. [ABSTRACT FROM AUTHOR]

In this paper, we prove that ζ cannot be a solution to any nontrivial algebraic differential equation whose coefficients are polynomials in Γ , Γ (n) and Γ (ℓ n) over the ring of polynomials in C , where ℓ , n ≥ 1 are positive integers. [ABSTRACT FROM AUTHOR]

Solvents that support protein functionality are important for biochemical applications, and new solvents are required. Here we employ FTIR and fluorescence spectroscopies, small angle X-ray scattering (SAXS) and X-ray crystallography to understand conformational changes of lysozyme with ionic liquids (ILs) added. Spectroscopic techniques identified that the secondary structure of lysozyme was maintained at the lower IL concentrations of 1 and 5 mol%, though the Tryptophan environment was significantly altered with nitrate-based ILs present. SAXS experiments indicated that the radius of gyration of lysozyme increased with 1 mol% IL present, and then decreased with increasing IL concentrations. The tertiary structure, particularly the loop regions, changed as a function of IL concentration, and this depended on the IL type. The crystallographic structure of lysozyme with the IL of ethylammonium nitrate present confirmed the loop region was extended, and identified three specific binding sites with nitrate ions, and that the positively charged areas were IL sensitive regions. This work provides a detailed understanding of lysozyme conformational changes in the presence of ILs. This approach can be extended to other functionally-important proteins. [ABSTRACT FROM AUTHOR]

The impact of the urban morphology on greenhouse gas emission is one of the key issues on global climate change. Since the urban form is directly related to the spatial distribution of urban land use, it is necessary to investigate the relation between carbon emission and different land use categories. In this paper, the city of Eindhoven (230,000 inhabitants) was used as a case study. According to the main road network, the entire city is divided into 6754 irregular patterns. Agglomerative cluster analysis was conducted to classify the patterns into 14 valid land use categories based on their land use function and land cover composition namely: agriculture, transport, retail trade, green space (with 3 sub-categories), residential (with 7 sub-categories), and others. The random forest algorithm was applied to select the significant features and to measure the relation between land use and carbon emission. The results have shown the importance of various landscape metrics on the carbon emission in each land use category. The most significant landscape metric is selected to describe the impact of spatial attributes on carbon emission. The outcomes show the carbon emission distribution of each land use category in the city. The retail trade and residential land use categories contribute a large proportion of carbon emission, terrace houses produce more carbon emission than other residential building categories. The combination of mid-rise buildings and low-rise buildings has a higher probability to produce more carbon emission. The assessment results can provide important support for the low carbon city spatial planning. • Statistics of landscape metrics shows high reliability on land use classification. • Random forest and hierarchical clustering improve classification performance. • CO 2 emission in the residential area is significantly influenced by building layout. • Knowledge of the relation of land use and CO 2 emission supports fine scale plan. [ABSTRACT FROM AUTHOR]

Previous studies showed that Nel-like molecule-1 (Nell-1) can positively regulate odontoblastic differentiation and dentin formation. Intriguingly, our group found that Nell-1 is co-expressed with neural markers. The purpose of this study was to investigate whether Nell-1 protein plays a regulatory role in the differentiation of dental pulp cells into neural-like cells by in vivo and in vitro studies. The expression patterns of Nell-1 and dental pulp neural markers were observed by double immunofluorescence staining in normal dental pulp tissue sections of Wistar rat. Collagen sponge containing Nell-1 protein was added into the pulp cavity of rat molars in order to observe the expression patterns of neural markers in rat dental pulp repair and regeneration model by immunohistochemical staining. Moreover, human dental pulp stem cells (hDPSCs) were cultured, and different concentrations of Nell-1 protein were added for 12 h, 24 h, and 72h. The expression of neural markers was detected by using quantitative real-time polymerase chain reaction and Western blot. Nell-1 was co-expressed with neural markers including substance P (SP) and Nestin in rat dental pulp tissue. The expression of neural markers including SP, neuron-specific enolase (NSE), and Nestin was increased obviously in rat dental pulp tissues stimulated with Nell-1 protein. In cultured hDPSCs induced by Nell-1 protein, the expression of neural markers including glial fibrillary acidic protein (GFAP), Nestin, and β-III tubulin was increased. Nell-1 plays a positive role in inducing the differentiation of DPSCs into neural-like cells. • Nell-1 is co-expressed with neural markers in pulp, which indicates that Nell-1 might be expressed in dental pulp nerve. • The expression levels of neural markers were increased in rat pulp and in cultured hDPSCs stimulated with Nell-1 protein. • This is the first study to demonstrate the effect of Nell-1 on dental pulp cells neural-like differentiation. [ABSTRACT FROM AUTHOR]

Abstract As one of the mucosal lymphatic tissues, the gill is an important immune organ in fish. Water environmental pollutants enter fish body through the gill. Therefore, the gill is the initial site where pollutants produce toxic effects in water. Chlorpyrifos (CPF), a broad-spectrum organophosphate insecticide, is widely used for agricultural pests and causes river pollution. In the present study, we investigated histopathological effect, oxidative stress indexes (SOD, GSH, T-AOC, and MDA), and apoptosis-related genes (P53, PUMA, Bax, Bcl-2, Apaf-1, Caspase-9, and Caspase-3) in the gills of common carp exposed to CPF. The results indicated that CPF exposure decreased SOD, T-AOC, and GSH; increased MDA; decreased Bcl-2 mRNA expression; and increased P53, PUMA, Bax, Apaf-1, Caspase-9, and Caspase-3 mRNA expressions in common carp gills. Our results proved that CPF exposure caused oxidative stress and apoptosis in common carp gills; CPF exposure destroyed the structural integrity and affected the immune function through oxidative stress and apoptosis in common carp gills. These will provide evidence for the toxic effects of water environmental pollutants on immune function and structural integrity in fish gills. Graphical abstract Image 1 Highlights • CPF caused oxidative stress in common carp gills. • CPF caused apoptosis via P53-mitochondria-Caspase-3 pathway in common carp gills. • Oxidative stress was involved in CPF-caused apoptosis in carp gills. • CPF destroyed structural integrity and affected immune function in carp gills. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), one of the widely known endocrine-disrupting chemicals, can be effectively degraded by advanced oxidation processes in water because of the powerful reactive oxygen species. In this study, Fenton, UV/Fenton, and metal ion/peroxymonosulfate (PMS) processes were compared to investigate BPA degradation efficiency and pathways initiated by hydroxyl radicals and sulfate radicals. In contrast to the Fenton system, which only degraded 60% of BPA within 15 min, the UV/Fenton system could degrade greater than 80% of BPA, because more hydroxyl radicals (•OH) were generated under the reduction of Fe3+ to Fe2+. The optimized parameters of the UV/Fenton system were as follows: 8 μmol/L of Fe2+, 80 μmol/L of H 2 O 2 , and a pH value of 3.0. As for the metal ion/PMS system, the BPA degradation efficiency was closely associated with the applied metal ions, and the order was as follows: Co2+/PMS (∼100%) > Fe2+/PMS (∼80%) > Cu2+/PMS (∼79%). The degradation pathways of BPA were theoretically interpreted through density functional theory prediction and degradation products during various processes. Two major initial reaction sites (4C and 6C) for •OH initiated using the UV/Fenton system and one initial reaction site (4C) for sulfate radicals (SO 4 •−) using the metal ion/PMS system were recognized for BPA degradation processes. The degradation products by •OH showed a larger average molecular weight than those by SO 4 •−. These studies are instructive for the application of different advanced oxidation systems in the treatment process of BPA in wastewater. •The degradation behaviors of BPA by various advanced oxidation methods were investigated. •BPA degradation mechanisms by.•OH and SO 4 •− were comprehensively investigated. •DFT theoretical calculations were used to estimate BPA degradation pathways. [ABSTRACT FROM AUTHOR]

Deriving knowledge and learning from past experiences is essential for the successful adoption of Nature-Based Solutions (NBS) as novel integrative solutions that involve many uncertainties. Past experiences in implementing NBS have been collected in a number of repositories; however, it is a major challenge to derive knowledge from the huge amount of information provided by these repositories. This calls for information systems that can facilitate the knowledge extraction process. This paper introduces the NBS Case-Based System (NBS-CBS), an expert system that uses a hybrid architecture to derive information and recommendations from an NBS experience repository. The NBS-CBS combines a 'black-box' artificial neural networks model with a 'white-box' case-based reasoning model to deliver an intelligent, adaptive, and explainable system. Experts have tested this system to assess its functionality and accuracy. Accordingly, the NBS-CBS appears to provide inspirational recommendations and information for the NBS planning and design process. • Learning from experience is essential for enhancing the uptake of NBS. • A case-based system (NBS-CBS) is developed and tested in a Dutch city. • NBS-CBS integrates an artificial neural network with a case-based reasoning model. • NBS-CBS supports the extraction of knowledge from an NBS repository. • NBS-CBS recommends NBS measures and accordingly finds relevant past experiences. [ABSTRACT FROM AUTHOR]

Ammonia (NH 3) is a hazardous substance to human and animal health. Selenium (Se) is an essential micronutrient with multiple health benefits. The present study aimed to verify whether and how Se supplementation has a protective role against NH 3 mediated-nephrotoxicity in pigs. A Se-NH 3 interaction model was established in pigs and the kidney samples were collected after a 30-day treatment period. The results showed that NH 3 exposure inhibited the PI3K/AKT/mTOR pathway and enhanced the secretion of inflammatory cytokines to induce autophagy and inflammation. Se can regulate the PI3K/AKT/mTOR pathway and attenuate the secretion of inflammatory cytokines altered by NH 3 to reduce autophagy and inflammation. In addition, Se co-treatment inhibited ROS production, elevated the activities of antioxidant systems, and increased the expression of 13 selenoproteins in pig kidneys caused by NH 3 exposure. These results implied that L -selenomethionine can moderate NH 3 -induced nephrotoxicity in pigs. Our study gives new ideas for the specific mechanism of NH 3 nephrotoxicity and provides a reference for comparative medicine and clinical medication. [Display omitted] • Excess NH 3 induced inflammatory damage in pig kidneys. • NH 3 led to autophagy through inhibition of PI3K/AKT/mTOR pathway. • 0.50 mg/kg of Se showed a nephroprotective effect against NH 3. • Selenoproteins contributed to the detoxification of NH 3 by Se. [ABSTRACT FROM AUTHOR]

Carboxymethyl chitosan has anti-bacterial activity and good coating forming ability, and glutathione has antioxidant and browning-inhibiting capacity. This study investigated the effects of carboxymethyl chitosan-based coatings alone (1% carboxymethyl chitosan) or loaded with glutathione (1% carboxymethyl chitosan + 0.2% glutathione) on the refrigeration of harvested enoki mushrooms (Flammulina velutipes) for preservation. Compared with the control group, all the treated samples exhibited decreased total viable count, respiratory rate, weight loss and browning degree and increased soluble solid content and sensory overall likeness after 12 days of refrigeration (P < 0.05). Additionally, carboxymethyl chitosan-based coatings incorporated with glutathione were more efficient for the preservation of enoki mushrooms than carboxymethyl chitosan-based coatings alone. Therefore, treatment with carboxymethyl chitosan-based coatings could be a promising preservation method for harvested enoki mushrooms. • Chitosan coatings reduced total viable count in mushrooms. • Chitosan coatings decreased respiratory rate and weight loss of mushrooms. • Chitosan coatings increased soluble solid content in mushrooms. • Chitosan inhibited browning in mushrooms. • Chitosan coatings improved overall likeness of mushrooms. [ABSTRACT FROM AUTHOR]

In this short paper we study the Sobolev function property of the Rayleigh 's quotient δ ( q ) = inf u ∈ E 1 , p ( U ) ⁡ ‖ u ‖ ∇ p ‖ u ‖ q , ∂ U p as a function of q ∈ [ 1 , p ⁎ ] for p ⁎ = p ( N − 1 ) N − p when p ∈ ( 1 , N ) , as well as the asymptotic behavior of positive solutions with minimal energy of the following problem − Δ p u = 0 in U , subject to | ∇ u | p − 2 ∂ u ∂ ν = λ | u | q − 2 u on ∂ U to the first p -harmonic Steklov eigenpair on an exterior region U ⊊ R N when N ≥ 3 . [ABSTRACT FROM AUTHOR]

Despite the obvious clinical interest, our understanding of how developmental mechanisms are redeployed during degeneration and regeneration after brain and spinal cord injuries remains quite rudimentary. In animal models of spinal cord injury, although spontaneous regeneration of descending axons is limited, compensation by intact corticospinal axons, descending tracts from the brainstem, and local intrinsic spinal networks all contribute to the recovery of motor function. Here, we investigated spontaneous motor compensation and plasticity that occur in the absence of corticospinal tract, using Celsr3|Emx1 mice in which the corticospinal tract is completely and specifically absent as a consequence of Celsr3 inactivation in the cortex. Mutant mice had no paresis, but displayed hyperactivity in open-field, and a reduction in skilled movements in food pellet manipulation tests. The number of spinal motoneurons was reduced and their terminal arbors at neuromuscular junctions were atrophic, which was reflected in electromyography deficits. Rubrospinal projections, calretinin-positive propriospinal projections, afferent innervation of motoneurons by calretinin-positive segmental interneurons, and terminal ramifications of monoaminergic projections were significantly increased. Contrary to control animals, mutants also developed a severe and persistent disability of forelimb use following the section of the rubrospinal tract at the C4 spinal level. These observations demonstrate for the first time that the congenital absence of the corticospinal tract induces spontaneous plasticity, both at the level of the motor spinal cord and in descending monoaminergic and rubrospinal projections. Such compensatory mechanisms could be recruited in case of brain or spinal cord lesion or degeneration. [ABSTRACT FROM AUTHOR]

Abstract: This paper treats some variational principles for solutions of inhomogeneous p-Laplacian boundary value problems on exterior regions with dimension . Existence-uniqueness results when are provided in a space of functions that contains . Functions in are required to decay at infinity in a measure theoretic sense. Various properties of this space are derived, including results about equivalent norms, traces and an -imbedding theorem. Also an existence result for a general variational problem of this type is obtained. [Copyright &y& Elsevier]

Zein possesses strong self-assembly ability due to its amphiphilicity. To investigate the effect of solvent polarity on both the flexibility of zein and the formation of flexible zein nanoparticles, various ethanol aqueous solutions were chosen. Alkaline modification was applied to improve the flexibility of the zein and a liquid-liquid method was used to produce zein nanoparticles. Solvent polarity plays a positive role in improving the flexibility of zein. Furthermore, native and flexible zein nanoparticles were formed from native zein and flexible zein, respectively. However, nanoparticles could not form from highly flexible zein due to their strong adaptability to changes in solvent. Compared with the emulsifying activity index (EAI) and emulsifying stability index (ESI) of native zein nanoparticles, a higher EAI and ESI of flexible zein nanoparticles were acquired. These results may be attributed to the strong adaptability of flexible zein to the medium changing through changing their secondary structure. Furthermore, the adaptability of flexible zein nanoparticles significantly depended on the initial polarity of the solvent. The deamidation reaction of zein was responsible for the change in zein flexibility. These findings thus provide clear evidence of the relationship between the solvent polarity and structural flexibility of modified zein. [Display omitted] • Effects of complex factors on formation of flexible zein nanoparticles were explored. • Strong polarity of solvent promoted the improvement of zein molecular flexibility. • Too high molecular flexibility inhibited the formation of zein nanoparticles. • Appropriate flexibility of zein molecule was positive to form nanoparticles. • The flexible zein nanoparticles have good environmental adaptability. [ABSTRACT FROM AUTHOR]

Ammonia (NH 3) emission is a common threat to farm animals. Selenium (Se) is known for its antioxidant property and can resist several stressors affecting farm animals. The aims of this study were (Ⅰ) to determine how excess NH 3 exert nephrotoxic effects in pigs and (Ⅱ) to investigate whether selenomethionine has an alleviative effect on NH 3 toxicity. Two diets supplemented with different doses of Se (0.22 mg/kg or 0.50 mg/kg) and two concentrations of NH 3 (< 5 mg/m3 or 89.8 mg/m3) were used in a 2 × 2 factorial design trial for a period of 30 days. The results showed that NH 3 exposure caused apoptosis and increased the number of apoptotic cells in pig kidneys. Further, the activities of antioxidant enzymes were decreased, and the transcriptional and translational levels of endoplasmic reticulum stress-related genes, Bcl-2 and Caspase family members were increased under NH 3 exposure. In addition, Wnt/β-catenin signaling pathway was suppressed after NH 3 treatment. Dietary supplement with selenomethionine appears to offer protection against NH 3 -induced kidney injury in pigs and the pathologic changes above were alleviated. Our findings provide additional insight into the mechanism of NH 3 toxicity in pigs while elucidating the role of Se as a potential antidote against NH 3 poisoning. [Display omitted] • Excess NH 3 induced apoptosis in pig kidneys. • ER stress, Bcl-2 and Caspase family members participated in apoptosis. • Selenomethionine had an alleviative effect on NH 3 toxicity. • Antioxidant and Wnt/β-catenin pathway linked with detoxification effect of Se. [ABSTRACT FROM AUTHOR]

The process of replacing animal proteins with plant-based proteins is still faced with the uncertain structural and processing properties of the isolated plant proteins. This study evaluated pea proteins obtained by dry (air classification combined with electromagnetic separation) and wet (isoelectric point precipitation) separation at the process-function-product level. The results showed that there was a significant difference in the purity of the isolated pea proteins obtained by dry (72.3 ± 0.7 g/100 g) and wet (89.2 ± 0.5 g/100 g) separation. High performance liquid chromatography, SDS gel electrophoresis and fluorescence analysis techniques showed that the dry-separated proteins maintained their native structure and presented excellent solubility and water absorption property, which lead to a porous and soft meat analogue. Although the wet separation resulted in denaturation of the protein, the essential amino acids contents were closer to the recommended level. Due to its higher purity, wet-separated proteins had better emulsification and foaming properties, and the resulting dough was more solid-like with higher hardness than dry-separated proteins. This study allowed a deeper understanding of pea proteins obtained by dry and wet separation and their potential use in the development of meat analogues. [Display omitted] • Wet separation improves the ratio of essential amino acids in pea proteins. • Dry separation maintains the natural structure and composition of the proteins. • Dry protein concentrate has high solubility and water holding capacity. • High purity wet protein isolate has better emulsification and foaming properties. • The meat analogues prepared by dry protein concentrate are soft and juicy. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a typical pollutant and carcinogen in environment. Exposure assessment of contaminants is an important component of occupational and environmental epidemiological studies. Early studies of Cd have focused on aquatic animals, chickens and rats. However, toxicological evaluation of Cd in pigs has not been reported. Therefore, twelve pigs were randomly divided into two groups (n = 6): the control group and the Cd group (Cd content: 15 ± 0.242 mg/kg feed) in this study, the experimental period was 30 d, and the toxic effects of Cd on the liver of weanling piglets were examined by antioxidant function, liver function, Cd content, histological examination and transcriptomics. The results showed that the changes of antioxidant function, liver function and Cd content were significant in the liver. Transcriptional profiling results showed that 399 differentially expressed genes (DEGs) were significantly up-regulated while 369 DEGs were remarkably down-regulated in Cd group, and which were concentrated in three ontologies: molecular function, cellular component and biological processes. Interestingly, significant changes in some genes of the cytochrome P450 enzyme (CYP450) and solute carrier (SLC) families have been observed and were consistent with qRT-PCR results. In conclusion, Cd could cause liver injury in weanling piglets and change the transcriptomic characteristics of liver. CYP450 and SLC families play an indispensable role in Cd-mediated hepatotoxicity. Importantly, changes in mRNA levels of CYP2B22, CYP7A1, CYP8B1, SLC26A8, SLC11A1, SLC27A2 and SLC22A7 induced by Cd have been reported for the first time. Our findings will provide a new insight for better assessing the mechanism of Cd toxicity to the liver. ga1 • Cadmium (Cd) exposure can cause liver damage in weaned piglets. • Cd exposure changed transcriptomic characteristics of liver in weanling piglets. • CYP450 and SLC families play an indispensable role in Cd-mediated hepatotoxicity. • Cd can cause the changes of CYP2B22, CYP7A1, and CYP8B1. • Our study proves for the first time that Cd causes the changes in SLC family genes. [ABSTRACT FROM AUTHOR]

Ammonia (NH 3), an environmental pollutant, poses a serious threat to human and avian health. Although previous studies have showed that NH 3 caused kidney injury, the molecular mechanisms of nephrotoxicity induced by NH 3 remain unclear. To explore the mechanisms of NH 3 nephrotoxicity, a total of 36 broiler chicks at one day of age were exposed to NH 3. After 42 days of exposure, blood samples were collected to determine creatinine and uric acid; and kidney samples were weighted and then collected to detect ultrastructural changes, oxidative stress parameters, ATPases, necroptosis- and mitochondrial dynamics-related genes. The results showed that chickens exposed to NH 3 showed lower relative kidney weight and an increase concentration in serum creatinine and uric acid. NH 3 exposure caused nephrocyte necrosis and increased the expression of necroptosis-related genes (TNF-α, RIPK1, RIPK3, MLKL, and JNK). Besides, the activities of antioxidant systems (SOD, CAT, GSH-Px, and T-AOC) were reduced, whereas the concentrations of H 2 O 2 and MDA were elevated. Lower activities of ATPases were obtained in NH 3 treatment groups. Furthermore, the mitochondrial fission-related genes drp1 and mff were activated, and mitochondrial fusion-related genes opa1, mfn1 and mfn2 were suppressed after NH 3 exposure. Based on the above results, we conclude that NH 3 caused-oxidative stress and mitochondrial dysfunction mediated nephrocyte necroptosis in chickens. This study may provide new insight into NH 3 nephrotoxicity. Image 1 • Excess NH 3 results in tissue damage and necrosis in chicken kidneys. • NH 3 induces nephrocyte necroptosis through RIP1-RIP3-MLKL pathway. • Oxidative stress and mitochondrial dysfunction co-contribute to necroptosis. [ABSTRACT FROM AUTHOR]

Cities increasingly have to find innovative ways to address challenges arising from climate change and urbanization. Nature-based solutions (NBS) have been gaining attention as multifunctional solutions that may help cities to address these challenges. However, the adoption and implementation of these solutions have been limited due to various barriers. This study aims to identify a taxonomy of dominant barriers to the uptake and implementation of NBS and their relationships. Fifteen barriers are identified from the literature and expert interviews and then ranked through a questionnaire. Interpretive Structural Modeling (ISM) serves to identify the mutual interdependencies among these barriers, which results in a structural model of six levels. Subsequently, Cross-impact matrix multiplication applied to classification (MICMAC analysis) is used to classify the barriers into four categories. The results suggest that political, institutional and knowledge-related barriers are the most dominant barriers to NBS. Cities that intend to apply NBS can draw on these findings, especially by more effectively prioritizing and managing their actions. • Barriers to the uptake and implementation of NBS are highly interdependent. • Identifying the interdependencies is essential for addressing barriers strategically. • The six-level ISM model illustrates the interdependencies among barriers. • Political, institutional and knowledge barriers are the most influential ones. • To spur the adoption of NBS, more engagement of policymakers is needed. [ABSTRACT FROM AUTHOR]

Ammonia (NH 3) is considered as environmental pollutant and toxic agent for animals and humans including poultry. Previous reports demonstrated that NH 3 suppressed broilers immunity. However, the harmful effects of NH 3 on broilers bursa of fabricius (BF) is still unknown. Functionally, apoptosis is very important for many physiological processes including homeostasis of lymphocyte population. Therefore, the present study was aimed to investigate the underlying mechanisms of NH 3 toxicity in the broilers BF. Histological observation showed lymphocyte accumulation, cavities and increased interstitial cells in BF. Ultrastructural observation indicated mitochondrial vacuoles, deformation and disappearance of mitochondrial membranes. Oxidative stress markers (CAT, MDA, H 2 O 2 , GGT, GSH-Px and GSH) showed that NH 3 -induced oxidative stress in BF. Meanwhile, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed increased apoptotic cells. In addition, the mRNA and protein expression of dynamin-related protein 1 (Drp1), mitochondrial fission factor (Mff), mitofusin 1 and 2 (Mfn1 and Mfn2), optic atrophy 1 (Opa1) indicated imbalance between mitochondrial inner and outer membrane and results in mitochondrial dysfunction in broilers BF. The mRNA and protein expression of apoptosis-related genes including Caspase-3, Caspase-9, Caspase-8, Cytochrome-C (Cyt-C), p53, B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) were significantly altered in broilers BF. Conclusively, these results displayed that excessive NH 3 causes BF damage and mitochondrial dysfunction through oxidative stress and apoptosis in BF and could affect immune function of BF. These findings provide possible therapeutic targets to prevent NH 3 induced toxicity in the BF of broilers. • The effects of ammonia (NH 3)-induced toxicity in broilers BF were investigated. • NH 3 -induced abnormal morphological and ultrastructural changes in the BF of broilers. • NH 3 inhalation causes a significant increase in oxidative stress and induced apoptosis. • The study provide possible therapeutic targets to prevent NH 3 -induced immune toxicity. [ABSTRACT FROM AUTHOR]

In this paper, we study the existence and multiplicity results of nontrivial positive solutions to the following quasilinear elliptic equation on R N , when N ≥ 2 , − Δ p u = λ K (x) u r − 1 − V (x) u q − 1. Here, K (x) , V (x) > 0 are suitable potentials, 1 < p < r < q < ∞ , and λ > 0 is a parameter. To study this problem, some compact embedding results regarding M V q , p (R N) ↪ L K r (R N) are proved that unify and extend some recent results of the author [12–14]. [ABSTRACT FROM AUTHOR]

• cdc55 null mutant grows slowly as pseudohyphae with some cells lacking the nucleus. • rts1 null mutant cells are round and enlarged and seem to undergo incomplete cell separation producing multinucleated cells. • Strong chitin deposition occurs at the septum of cdc55 null mutant cells and on the surface of rts1 null mutant cells. • Deletion of cdc55 exhibits severe defects in hyphal and biofilm formation, while deletion of rts1 is partially defective. • cdc55 and rts1 null mutants show reduced virulence in mice. Protein phosphatase-2A (PP2A) is a heterotrimeric enzyme composed of a catalytic subunit, a regulatory subunit, and a structural subunit. In Candida albicans , Cdc55 and Rts1 have been identified as possible regulatory subunits of PP2A containing the catalytic subunit Pph21 and structural subunit Tpd3. The Tpd3-Pph21 phosphatase regulates cell morphogenesis and division. However, the functions of Cdc55 and Rts1 remain unclear. Here, we constructed cdc55 Δ/Δ and rts1 Δ/Δ mutants and found that they exhibit different defects in multiple phenotypes although both show similar hyperphosphorylation of the septin Sep7 and aberrant septin organization. Under yeast growth conditions, the cdc55 Δ/Δ mutant grows slowly as pseudohyphae with some cells lacking the nucleus, while rts1 Δ/Δ cells are round and enlarged and seem to undergo incomplete cell separation producing multinucleated cells. Strong chitin deposition occurs at the septum of cdc55 Δ/Δ cells and on the surface of rts1 Δ/Δ cells, which likely contributes to increased susceptibility to caspofungin. Also, cdc55 Δ/Δ exhibits severe defects in hyphal and biofilm formation, while rts1 Δ/Δ is partially defective. Both mutants show reduced virulence in mice, suggesting that PP2A-B subunits could serve as potential antifungal targets. [ABSTRACT FROM AUTHOR]

[Display omitted] Understanding protein behaviour is crucial for developing functional solvent systems. Ionic liquids (ILs) are designer salts with versatile ion combinations, where some suppress unfavourable protein behaviour. This work utilizes small angle X-ray scattering (SAXS) to investigate the size and shape changes of model protein hen egg white lysozyme (HEWL) in 137 IL and salt solutions. Guinier, Kratky, and pair distance distribution analysis were used to evaluate the protein size, shape, and aggregation changes in these solvents. At low IL and salt concentration (1 mol%), HEWL remained monodispersed and globular. Most ILs increased HEWL size compared to buffer, while the nitrate and mesylate anions induced the most significant size increases. IL cation branching, hydroxyl groups, and longer alkyl chains counteracted this size increase. Common salts exhibited specific ion effects, while the IL effect varied with concentration due to complex ion-pairing. Protein aggregation and unfolding occurred at 10 mol% IL, altering the protein shape, especially for ILs with multiple alkyl chains on the cation, or with a mesylate/nitrate anion. This study highlights the usefulness of adopting a high-throughput SAXS strategy for understanding IL effects on protein behaviour and provides insights on controlling protein aggregation and unfolding with ILs. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • PAH1 deletion increases cell death in Candida albicans. • pah1 null mutant exhibits increased stress sensitivity and defects in hyphal growth. • PAH1 deletion decreases the expression levels of EFG1 , FLO8 and CPH1. • PAH1 deletion increases intracellular ROS and high levels of ROS inhibit the hyphal growth. • PAH1 deletion attenuates C. albicans virulence in mice. Abstract Phosphatidate phosphatases play essential roles in lipid metabolism by converting phosphatidic acid to diacylglycerol. Here, we have investigated the roles of a phosphatidate phosphatase, Pah1, in the fungal pathogen Candida albicans. Deleting PAH1 causes multiple phenotypes, especially severe hyphal defects, increased sensitivity to cell wall stress, and reduced virulence in mice. By qPCR, we detected a significant downregulation of hyphal-specific genes including two key hyphal-promoting genes UME6 and HGC1. Overexpression of UME6 in pah1 Δ/Δ cells largely restored the hyphal growth, indicating that the reduced expression of UME6 is primarily responsible for the hyphal defects. We also detected decreased expression of three hyphal-promoting transcription factors EFG1 , FLO8, and CPH1 in pah1 mutants, consistent with the reduced expression of UME6. Furthermore, the pah1 Δ/Δ mutant exhibited increased sensitivity to cell wall stress. During systemic infection of mice, the mutant showed significantly impaired ability to colonize the kidney and to kill the host. Together, C. albicans PAH1 plays an important role in hyphal growth, adaptability to environmental stresses, and virulence. Thus, Pah1 could be targeted for the development of new antifungal drugs. [ABSTRACT FROM AUTHOR]

Pediococcus pentosaceus , Lactobacillus curvatus , Lactobacillus sakei and Staphylococcus xylosus were evaluated to determine their roles in the lipolysis and lipid oxidation in Harbin dry sausages and their relation to flavour development. The free fatty acid (FFA) contents of both muscle and fat tissues were higher in the inoculated sausages than those of the non-inoculated control, especially with mixed strains ( P < 0.05). The predominant FFAs in both tissues at the end of the fermentation were palmitic acid, stearic acid and oleic acid. The inoculation of dry sausages with bacterial strains, especially mixed strains, significantly decreased the peroxide value and thiobarbituric acid reactive substances ( P < 0.05). Furthermore, a lower level of volatile compounds related to lipid-oxidation, such as aldehydes, ketones and hydrocarbons, was observed in the inoculated sausage ( P < 0.05). The results demonstrate that Harbin dry sausage can be inoculated with a starter culture mixture of P. pentosaceus , L. curvatus and S. xylosus to promote lipid hydrolysis, inhibit lipid autoxidation and improve fermented flavour development. [ABSTRACT FROM AUTHOR]

Nel-like molecule 1 (Nell-1) is an essential positive regulator of tooth development and odontoblast differentiation. However, its precise mechanism remains undetermined. This study aims to explore the possible receptor or binding protein of Nell-1. Results showed that Nell-1 and Apoptosis related protein 3(APR3) expression levels were high in odontoblasts and inversely correlated. Endogenous Nell-1 co-immunoprecipitated with APR3, and this co-IP was reciprocal. Double immunofluorescence staining revealed that Nell-1 and APR3 colocalized on the nuclear envelope of human dental pulp cells. Nell-1 inhibited the proliferation of these cells co-infected with APR3 through Cyclin D1 downregulation. The interaction of Nell-1 with APR3 stimulated alkaline phosphatase (ALP) activity and promoted the expression and mineralization of DSPP, ALP, OPN, and BSP. The shRNA of APR3 decreased cell differentiation and mineralization. Nell-1 could reciprocally interact with APR3 and stimulate the differentiation and mineralization of human dental pulp cells. Future studies should explore the potential functional connection and the molar mechanism of such interaction. • Nell-1 as a secreted protein stimulates human dental pulp cells proliferation and differentiation and induces teeth formation and regeneration. • Nell-1 and APR3, which were both expressed in the dental pulp stem cells, had similar spatiotemporal expression patterns. Nell-1 and APR3 proteins were primarily present in the cytosol. • Nell-1 could reciprocally interact with APR3 and stimulate the differentiation and mineralization of human dental pulp cells. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) can cause locomotor dysfunctions and sensory deficits. Evidence shows that functional nanodrugs can regulate macrophage polarization and promote anti-inflammatory cytokine expression, which is feasible in SCI immunotherapeutic treatments. Molybdenum disulfide (MoS 2) nanomaterials have garnered great attention as potential carriers for therapeutic payload. Herein, we synthesize MoS 2 @PEG (MoS 2 = molybdenum disulfide, PEG = poly (ethylene glycol)) nanoflowers as an effective carrier for loading etanercept (ET) to treat SCI. We characterize drug loading and release properties of MoS 2 @PEG in vitro and demonstrate that ET-loading MoS 2 @PEG obviously inhibits the expression of M1-related pro-inflammatory markers (TNF-α, CD86 and iNOS), while promoting M2-related anti-inflammatory markers (Agr1, CD206 and IL-10) levels. In vivo , the mouse model of SCI shows that long-circulating ET-MoS 2 @PEG nanodrugs can effectively extravasate into the injured spinal cord up to 96 h after SCI, and promote macrophages towards M2 type polarization. As a result, the ET-loading MoS 2 @PEG administration in mice can protect survival motor neurons, thus, reducing injured areas at central lesion sites, and significantly improving locomotor recovery. This study demonstrates the anti-inflammatory and neuroprotective activities of ET-MoS 2 @PEG and promising utility of MoS 2 nanomaterial-mediated drug delivery. [ABSTRACT FROM AUTHOR]

Although overexpression of eukaryotic translation initiation factor 4E (eIF4E) is associated with enhanced growth and poor prognosis in nasopharyngeal carcinoma (NPC), the function of eIF4E in NPC response to chemotherapy has not been revealed. In this work, we demonstrate that eIF4E inhibition using both ribavirin and siRNA targets NPC cells and enhances the efficacy of 5-fluorouracil (5-FU). Mechanism studies indicate that 5-FU treatment increases phosphorylation of eIF4E in NPC cells, and this is dependent on ERK activation. eIF4E inhibition thus significantly sensitizes NPC cell response to 5-FU. Of note, ribavirin is a clinically available anti-viral drug. We show that ribavirin exhibits preferential toxicity to NPC with normal nasopharyngeal epithelial cells largely unaffected. Ribavirin acts on NPC cells via inhibiting eIF4E/Akt signaling, and the suppression of eIF4E by ribavirin are not the consequence of inhibition of eIF4E upstream signaling: Mnk and mTOR. In two independent NPC xenograft mouse models, ribavirin at well-tolerated dose that significantly inhibited NPC growth as single drug alone and its combination with 5-FU completely arrests tumor growth throughout the whole duration of treatment, without causing toxicity in mice. Our findings provide the better understanding on the role of eIF4E in NPC in response to 5-FU and preclinical rationale to explore ribavirin as a sensitizing strategy to treat NPC, particularly in those who develop 5-FU resistance. • Ribavirin targets NPC in vitro and in vivo , and acts synergistically with 5-FU. • Ribavirin acts on NPC via inhibiting eIF4E/Akt. • Chemotherapy activates eIF4E in NPC cells in an Erk-dependent manner. • Ribavirin sensitizes NPC to 5-FU via inhibiting 5-FU-induced eIF4E activation. [ABSTRACT FROM AUTHOR]

The poor freeze-thaw stability of konjac glucomannan (KG) hydrogel will greatly affect its application in the frozen prepared foods. In this study, the filling effects of natural tapioca starch (TS) and corn starch (CS) on the properties of freeze-thaw KG hydrogel were evaluated. The addition of starches significantly improved the gel strength and water holding capacity and inhibited the freeze-induced syneresis of composite hydrogels, where CS is superior to TS. These beneficial effects could be the results of concurrent effects of the decrease of frequency dependence/freezing point, the formation of dense microstructure and the reinforced hydrogen bonds and hydrophobic interactions of composite hydrogels. The foregoing results suggested the potential feasibility of low-cost natural starches to improve the textural properties and freeze-thaw stability of KG hydrogels. • Strong interactions occurred between the konjac glucomannan and starches. • Addition of starch decreased the freezing-induced syneresis of composite gel. • Konjac glucomannan/starch composite gel exhibited well-arranged network structure. • Corn starch was superior to tapioca in improving the properties of the composite gel. [ABSTRACT FROM AUTHOR]

Recovery from spinal cord injury (SCI) and other central nervous system (CNS) trauma is hampered by limits on axonal regeneration in the CNS. Regeneration is restricted by the lack of neuron-intrinsic regenerative capacity and by the repressive microenvironment confronting damaged axons. To address this challenge, we have developed a therapeutic strategy that co-targets kinases involved in both extrinsic and intrinsic regulatory pathways. Prior work identified a kinase inhibitor (RO48) with advantageous polypharmacology (co-inhibition of targets including ROCK2 and S6K1), which promoted CNS axon growth in vitro and corticospinal tract (CST) sprouting in a mouse pyramidotomy model. We now show that RO48 promotes neurite growth from sensory neurons and a variety of CNS neurons in vitro, and promotes CST sprouting and/or regeneration in multiple mouse models of spinal cord injury. Notably, these in vivo effects of RO48 were seen in several independent experimental series performed in distinct laboratories at different times. Finally, in a cervical dorsal hemisection model, RO48 not only promoted growth of CST axons beyond the lesion, but also improved behavioral recovery in the rotarod, gridwalk, and pellet retrieval tasks. Our results provide strong evidence for RO48 as an effective compound to promote axon growth and regeneration. Further, they point to strategies for increasing robustness of interventions in pre-clinical models. • Kinase inhibitor RO48 targets both intrinsic and extrinsic axon-inhibitory pathways. • RO48 promotes neurite outgrowth in multiple neuronal types, including human neurons. • RO48 promotes corticospinal axon growth in injury models when delivered to cortex. • Axon growth induced by RO48 does not require an acute injury. • Results from distinct laboratories suggest that in vivo effects of RO48 are robust. [ABSTRACT FROM AUTHOR]