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Negative air ions (NAIs) have been discovered for more than 100 years and are widely used for air cleaning. Here, we have carried out a comprehensive reviewing on the effects of NAIs on humans/animals, and microorganisms, and plant development. The presence of NAIs is credited for increasing psychological health, productivity, and overall well-being but without consistent or reliable evidence in therapeutic effects and with controversy in anti-microorganisms. Reports also showed that NAIs could help people in relieving symptoms of allergies to dust, mold spores, and other allergens. Particulate matter (PM) is a major air pollutant that affects human health. Experimental data showed that NAIs could be used to high-efficiently remove PM. Finally, we have reviewed the plant-based NAI release system under the pulsed electric field (PEF) stimulation. This is a new NAI generation system which releases a huge amount of NAIs under the PEF treatment. The system may be used to freshen indoor air and reduce PM concentration in addition to enriching oxygen content and indoor decoration at home, school, hospital, airport, and other indoor areas.

The global expansion of rapeseed seed quality has been focused on maintaining glucosinolate (GSL) and erucic acid (EA) contents. However, the influence of seed GSL and EA contents on the germination process under drought stress remains poorly understood. Herein, 114 rapeseed accessions were divided into four groups based on GSL and EA contents to investigate their performance during seed imbibition under drought stress. Our results revealed significant variations in seed germination-related traits, particularly with higher GSL and EA, which exhibited higher germination % (G%) and lower mean germination time (MGT) under drought stress conditions. Moreover, osmoregulation, enzymatic system and hormonal regulation were improved in high GSL and high EA (HGHE) versus low GSL and low EA (LGLE) seeds, indicating the essential protective role of GSL and EA during the germination process in response to drought stress. The transcriptional regulation mechanism for coordinating GSL–EA-related pathways in response to drought stress during seed imbibition was found to involve the differential expression of sugar metabolism-, antioxidant-, and hormone-related genes with higher enrichment in HGHE compared to LGLE seeds. GO enrichment analysis showed higher variations in transcription regulator activity and DNA-binding transcription factors, as well as ATP and microtubule motor activity in GSL–EA-related pathways. Furthermore, KEGG analysis identified cellular processes, environmental information processing, and metabolism categories, with varied gene participation between GSL, EA and GSL–EA-related pathways. For further clarification, QY7 (LGLE) seeds were primed with different concentrations of GSL and EA under drought stress conditions. The results showed that 200 μmol/L of GSL and 400 μmol/L of EA significantly improved G%, MGT, and seedling fresh weight, besides regulating stress and fatty acid responsive genes during the seed germination process under drought stress conditions. Conclusively, exogenous application of GSL and EA is considered a promising method for enhancing the drought tolerance of LGLE seeds. Furthermore, the current investigation could provide a theoretical basis of GSL and EA roles and their underlying mechanisms in stress tolerance during the germination process.

Glycogen in the female lower reproductive tract is a major carbon source for colonization and acidification by common vaginal Lactobacillus species, such as Lactobacillus crispatus. Previously, we identified the amylopullulanase encoding gene pulA of Lactobacillus crispatus to correlate with the ability to autonomously utilize glycogen for growth. Here, we further characterize genetic variation and differential regulation of pulA affecting the presence of its gene product on the outer surface layer. We show that alpha-glucan degrading activity dissipates when Lactobacillus crispatus is grown on glucose, maltose and maltotriose, in agreement with carbon catabolite repression elements flanking the pulA gene. Proteome analysis of the S-layer confirmed that the amylopullulanase protein is highly abundant in an S-layer enriched fraction, but not in a strain with a defective amylopullulanase variant or in an amylopullulanase-sufficient strain grown on glucose. In addition, we provide evidence that Lactobacillus crispatus pulA mutants are relevant in vivo, as they are commonly observed in metagenome datasets of human vaginal microbial communities. Analysis of the largest publicly available dataset of 1507 human vaginal metagenomes indicates that among the 270 samples that contain a Lactobacillus crispatuspulA gene, 62 samples (23%) had a defective variant of this gene. Taken together, these results demonstrate that both environmental, as well as genetic factors explain the variation of Lactobacillus crispatus alpha-glucosidases in the vaginal environment.

Purinergic signaling may be altered in diabetes accounting for endothelial dysfunction. Uridine adenosine tetraphosphate (Up4A), a novel dinucleotide substance, regulates vascular function via both purinergic P1 and P2 receptors (PR). Up4A enhances vascular contraction in isolated arteries of diabetic rats likely through P2R. However, the precise involvement of PRs in endothelial dysfunction and the vasoconstrictor response to Up4A in diabetes has not been fully elucidated. We tested whether inhibition of PRs improved endothelial function and attenuated Up4A-mediated vascular contraction using both aortas and mesenteric arteries of type 2 diabetic (T2D) Goto Kakizaki (GK) rats vs. control Wistar (WT) rats. Endothelium-dependent (EDR) but not endothelium-independent relaxation was significantly impaired in both aortas and mesenteric arteries from GK vs. WT rats. Non-selective inhibition of P1R or P2R significantly improved EDR in aortas but not mesenteric arteries from GK rats. Inhibition of A1R, P2X7R, or P2Y6R significantly improved EDR in aortas. Vasoconstrictor response to Up4A was enhanced in aortas but not mesenteric arteries of GK vs. WT rats via involvement of A1R and P2X7R but not P2Y6R. Depletion of major endothelial component nitric oxide enhanced Up4A-induced aortic contraction to a similar extent between WT and GK rats. No significant differences in protein levels of A1R, P2X7R, and P2Y6R in aortas from GK and WT rats were observed. These data suggest that altered PR sensitivity accounts for endothelial dysfunction in aortas in diabetes. Modulating PRs may represent a potential therapy for improving endothelial function.

Lignin is nature's second most abundant vascular plant biopolymer, playing significant roles in mechanical support, water transport, and stress responses. This study identified 90 lignin biosynthesis genes in rice based on phylogeny and motif constitution, and they belong to PAL , C4H , 4CL , HCT , C3H , CCoAOMT , CCR , F5H , COMT , and CAD families. Duplication events contributed largely to the expansion of these gene families, such as PAL , CCoAOMT , CCR , and CAD families, mainly attributed to tandem and segmental duplication. Microarray data of 33 tissue samples covering the entire life cycle of rice suggested fairly high PAL , HCT , C3H , CCoAOMT , CCR , COMT , and CAD gene expressions and rather variable C4H , 4CL , and F5H expressions. Some members of lignin-related genes ( OsCCRL11 , OsHCT1 / 2 / 5 , OsCCoAOMT1 / 3 / 5 , OsCOMT , OsC3H , OsCAD2, and OsPAL1 / 6 ) were expressed in all tissues examined. The expression patterns of lignin-related genes can be divided into two major groups with eight subgroups, each showing a distinct co-expression in tissues representing typically primary and secondary cell wall constitutions. Some lignin-related genes were strongly co-expressed in tissues typical of secondary cell walls. Combined HPLC analysis showed increased lignin monomer (H, G, and S) contents from young to old growth stages in five genotypes. Based on 90 genes' microarray data, 27 genes were selected for qRT-PCR gene expression analysis. Four genes ( OsPAL9 , OsCAD8C , OsCCR8 , and OsCOMTL4 ) were significantly negatively correlated with lignin monomers. Furthermore, eleven genes were co-expressed in certain genotypes during secondary growth stages. Among them, six genes ( OsC3H , OsCAD2 , OsCCR2 , OsCOMT , OsPAL2 , and OsPAL8 ) were overlapped with microarray gene expressions, highlighting their importance in lignin biosynthesis.

Amoxicillin (AMX) is utilized in the treatment of several infectious diseases, and its concentration in wastewater has increased quite significantly over the years, posing high health hazards for humans and other living organisms. Investigations are in progress globally to eliminate AMX and other related pollutants using several methods that include adsorption, photolysis, photocatalytic degradation, photoelectrocatalytic degradation, and electrochemical conversion. AMX can be eliminated efficiently from the environment using photodegradation, either by photolysis or a photocatalytic process. Several types of semiconductor NMs have been used to eliminate AMX and other related drugs present in wastewater. This review spans the photodegradation studies conducted during the years 2018-2024 to degrade and eliminate AMX in aquatic systems. Several studies have been reported to eliminate AMX from different water streams. These studies are categorized into TiO 2 -containing and non-TiO 2 -based catalysts for better comparison. A section on photolysis is also included, showing the use of UV alone or with H 2 O 2 or PS without using any nanomaterial. A tabulated summary of both types of catalysts showing the catalysts, reaction conditions, and degradation efficiency is presented. Researchers have used a variety of reaction conditions that include radiation types (UV, solar, and visible), pH of the solution, concentration of AMX, number of nanomaterials, presence of other additives and activators such as H 2 O 2 as oxidant, and the influence of different salts like NaCl and CaCl 2 on the photodegradation efficiency. TiO 2 was the best nanomaterial found that achieved the highest degradation of AMX in ultraviolet irradiation. TiO 2 doped with other nanomaterials showed very good performance under visible light. WO 3 was also used by several investigators and found quite effective for AMX degradation. Other metal oxides used for AMX elimination were derived from molybdenum, zinc, manganese, copper, cerium, silver, etc. Some researchers have used UV and/or visible irradiation or sunlight, without using solid catalysts, in the presence of oxidants such as H 2 O 2 . A summarized description of earlier published reviews is also presented.

The auxin/indoleacetic acid ( Aux/IAA ) family plays a central role in regulating gene expression during auxin signal transduction. Nonetheless, there is limited knowledge regarding this gene family in sugarcane. In this study, 92 members of the IAA family were identified in Saccharum spontaneum , distributed on 32 chromosomes, and classified into three clusters based on phylogeny and motif compositions. Segmental duplication and recombination events contributed largely to the expansion of this superfamily. Additionally, cis-acting elements in the promoters of SsIAAs involved in plant hormone regulation and stress responsiveness were predicted. Transcriptomics data revealed that most SsIAA expressions were significantly higher in stems and basal parts of leaves, and at nighttime, suggesting that these genes might be involved in sugar transport. QRT-PCR assays confirmed that cold and salt stress significantly induced four and five SsIAAs , respectively. GFP-subcellular localization showed that SsIAA23 and SsIAA12a were localized in the nucleus, consistent with the results of bioinformatics analysis. In conclusion, to a certain extent, the functional redundancy of family members caused by the expansion of the sugarcane IAA gene family is related to stress resistance and regeneration of sugarcane as a perennial crop. This study reveals the gene evolution and function of the SsIAA gene family in sugarcane, laying the foundation for further research on its mode of action.

This study investigates the clustering patterns of human β-secretase 1 (BACE-1) inhibitors using complex network methodologies based on various distance functions, including Euclidean, Tanimoto, Hamming, and Levenshtein distances. Molecular descriptor vectors such as molecular mass, Merck Molecular Force Field (MMFF) energy, Crippen partition coefficient (ClogP), Crippen molar refractivity (MR), eccentricity, Kappa indices, Synthetic Accessibility Score, Topological Polar Surface Area (TPSA), and 2D/3D autocorrelation entropies are employed to capture the diverse properties of these inhibitors. The Euclidean distance network demonstrates the most reliable clustering results, with strong agreement metrics and minimal information loss, indicating its robustness in capturing essential structural and physicochemical properties. Tanimoto and Hamming distance networks yield valuable clustering outcomes, albeit with moderate performance, while the Levenshtein distance network shows significant discrepancies. The analysis of eigenvector centrality across different networks identifies key inhibitors acting as hubs, which are likely critical in biochemical pathways. Community detection results highlight distinct clustering patterns, with well-defined communities providing insights into the functional and structural groupings of BACE-1 inhibitors. The study also conducts non-parametric tests, revealing significant differences in molecular descriptors, validating the clustering methodology. Despite its limitations, including reliance on specific descriptors and computational complexity, this study offers a comprehensive framework for understanding molecular interactions and guiding therapeutic interventions. Future research could integrate additional descriptors, advanced machine learning techniques, and dynamic network analysis to enhance clustering accuracy and applicability.

Plant glutamate receptor-like channels (GLRs) are homologs of animal ionotropic glutamate receptors. GLRs are critical in various plant biological functions, yet their genomic features and functions in disease resistance remain largely unknown in many crop species. Here, we report the results on a thorough genome-wide study of the GLR family in oilseed rape ( Brassica napus ) and their role in resistance to the fungal pathogen Sclerotinia sclerotiorum . A total of 61 GLRs were identified in oilseed rape. They comprised three groups, as in Arabidopsis thaliana . Detailed computational analyses, including prediction of domain and motifs, cellular localization, cis -acting elements, PTM sites, and amino acid ligands and their binding pockets in BnGLR proteins, unveiled a set of group-specific characteristics of the BnGLR family, which included chromosomal distribution, motif composition, intron number and size, and methylation sites. Functional dissection employing virus-induced gene silencing of BnGLRs in oilseed rape and Arabidopsis mutants of BnGLR homologs demonstrated that BnGLR35 / AtGLR2.5 positively, while BnGLR12 / AtGLR1.2 and BnGLR53 / AtGLR3.2 negatively, regulated plant resistance to S. sclerotiorum , indicating that GLR genes were differentially involved in this resistance. Our findings reveal the complex involvement of GLRs in B. napus resistance to S. sclerotiorum and provide clues for further functional characterization of BnGLRs .

Complex microbial communities have been reported to be involved in endodontic infections. The microorganisms invade the dental pulp leading to pulpitis and initiating pulp inflammation. Fusobacterium nucleatum is a dominant bacterium implicated in both primary and secondary endodontic infections. Drugs targeting the molecular machinery of F. nucleatum will minimize pulp infection. LpxA and LpxD are early acyltransferases involved in the formation of lipid A, a major component of bacterial membranes. The identification of leads which exhibit preference towards successive enzymes in a single pathway can also prevent the development of bacterial resistance. A stringent screening strategy utilizing physicochemical and pharmacokinetic parameters along with a virtual screening approach identified two compounds, Lomefloxacin and Enoxacin, with good binding affinity towards the early acyltransferases LpxA and LpxD. Lomefloxacin and Enoxacin, members of the fluoroquinolone antibiotic class, exhibit wide-ranging activity against diverse bacterial strains. Nevertheless, their effectiveness in the context of endodontic treatment requires further investigation. This study explored the potential of Lomefloxacin and Enoxacin to manage endodontic infections via computational analysis. Moreover, the compounds identified herein serve as a foundation for devising novel combinatorial libraries with enhanced efficacy for endodontic therapeutic strategies.

Cadmium (Cd), being a highly toxic heavy metal, significantly impacts plant growth and development by altering nutrient uptake and causing oxidative and structural damage, resulting in reduced yield. To combat Cd toxicity and accumulation in wheat, it was hypothesized that co-application of Selenium (Se) and Silicon (Si) can reduce the adverse effect of Cd and regulate Cd resistance while improving Se fortification in wheat. Therefore, this study evaluated the comparative effect of Se and Si on the growth and antioxidant defense systems of wheat plants grown in a hydroponic setup. Briefly, the plants were acclimatized to the hydroponic solution for 1 week and then exposed to 10 µmol Cd. Afterwards, the treatments, including 0.2 mmol Si and 1.5 µmol Se, were applied as a root and foliar application, respectively. Plants supplemented with both Se and Si showed improved biomass and other physiological growth attributes, and this response was associated with improved activity/contents of antioxidants, including glutathione (GSH) content, glutathione reductase (GR), ascorbate peroxidase (APX), and catalase (CAT), with related lowering of hydrogen peroxide, malondialdehyde content, and structural damages. Moreover, by Se + Si supplementation, a decrease in total S levels in plant tissues was observed, whereas an increase in total protein concentration and GSH indicated a different and novel mechanism of Cd tolerance and S homeostasis in the plant. It was observed that Si was more involved in significantly reducing Cd translocation by stabilizing Cd in the root and reducing its content in the soluble fraction in both the root and shoot. Whereas Se was found to play the main role in reducing the oxidative damage caused by Cd, and the effect was more profound in the shoot. In addition, this study also observed a positive correlation between Si and Se for relative uptake, which had not been reported earlier. Our findings show that the Se and Si doses together benefit growth regulation and nutrient uptake; additionally, their combinations support the Cd resistance mechanism in wheat through upregulation of the antioxidant system and control of Cd translocation and subcellular distribution, ultimately contributing to the nutritional quality of wheat produced. Thus, it is concluded that the co-application of Se and Si has improved the nutritional quality while reducing the Cd risk in wheat and therefore needs to be employed as a potential strategy to ensure food safety in a Cd-contaminated environment.

Aside from its importance in human and animal health, low levels of foliar-applied selenate (SeO 4 ) can be advantageous in the presence of sulfur (S), contributing to improved growth, nutrient uptake, and crop quality. A hydroponic experiment in a growth chamber explored the interactive influence of Se and S on micronutrients and several quality indices, such as soluble sugars, organic acids, and total protein concentrations in spinach ( Spinacia oleracea L.). Three levels of S (deprivation, adequate, and excessive) with varying quantities of Se (deficient, moderate, and higher) were examined in combination. Under S starvation and along with S nourishment in plant parts, Se treatments were found to cause noticeable variations in plant biomass and the concentrations of the examined elements and other quality parameters. Both Se levels promoted S accumulation in S-treated plants. Although the Se treatment had the opposite effect in shoots, it had a favorable impact on minerals (apart from Mn) in roots grown under S-limiting conditions. The S and Se relationship highlighted beneficial and/or synergistic effects for Mn and Fe in edible spinach portions. Reducing sugars were synergistically boosted by adequate S and moderate Se levels in roots, while in shoots, they were accumulated under moderate-or-higher Se and excessive S. Furthermore, the concentration of the quantified organic acids under S-deficient conditions was aided by various Se levels. In roots, moderate Se under high S application enhanced both malic acid and citric acid, while in the edible parts, higher Se under both adequate and elevated S levels were found to be advantageous in malic acid accumulation. Moreover, by elevating S levels in plant tissues, total protein concentration increased, whereas both moderate and high Se levels (Se1 and Se2) did not alter total protein accumulation in high S-applied roots and shoots. Our findings show that the high S and medium Se dose together benefit nutrient uptake; additionally, their combinations support soluble sugars and organic acids accumulation, contributing ultimately to the nutritional quality of spinach plants. Moreover, consuming 100 g of fresh red spinach shoot enriched with different Se and S levels can contribute to humans' daily micronutrients intake.

Forebrain ischemia-reperfusion (IR) injury causes neurological impairments due to decreased cerebral autoregulation, hypoperfusion, and edema in the hours to days following the restoration of spontaneous circulation. This study aimed to examine the protective and/or therapeutic effects of cerebrolysin (CBL) in managing forebrain IR injury and any probable underlying mechanisms. To study the contribution of reperfusion to forebrain injury, we developed a transient dual carotid artery ligation (tDCAL/IR) mouse model. Five equal groups of six BLC57 mice were created: Group 1: control group (no surgery was performed); Group 2: sham surgery (surgery was performed without IR); Group 3: tDCAL/IR (surgery with IR via permanently ligating the left CA and temporarily closing the right CA for 30 min, followed by reperfusion for 72 h); Group 4: CBL + tDCAL/IR (CBL was given intravenously at a 60 mg/kg BW dose 30 min before IR); and Group 5: tDCAL/IR + CBL (CBL was administered i.v. at 60 mg/kg BW three hours after IR). At 72 h following IR, the mice were euthanized. CBL administration 3 h after IR improved neurological functional recovery, enhanced anti-inflammatory and antioxidant activities, alleviated apoptotic neuronal death, and inhibited reactive microglial and astrocyte activation, resulting in neuroprotection after IR injury in the tDCAL/IR + CBL mice group as compared to the other groups. Furthermore, CBL reduced the TLRs/NF-kB/cytokines while activating the Keap1/Nrf2/antioxidant signaling pathway. These results indicate that CBL may improve neurologic function in mice following IR.

Cryodamage affects the normal physiological functions and survivability of boar sperm during cryopreservation. Lysine acetylation is thought to be an important regulatory mechanism in sperm functions. However, little is known about protein acetylation and its effects on cryotolerance or cryodamage in boar sperm. In this study, the characterization and protein acetylation dynamics of boar sperm during cryopreservation were determined using liquid chromatography-mass spectrometry (LC-MS). A total of 1440 proteins were identified out of 4705 modified proteins, and 2764 quantifiable sites were elucidated. Among the differentially modified sites, 1252 were found to be upregulated compared to 172 downregulated sites in fresh and frozen sperms. Gene ontology indicated that these differentially modified proteins are involved in metabolic processes and catalytic and antioxidant activities, which are involved in pyruvate metabolism, phosphorylation and lysine degradation. In addition, the present study demonstrated that the mRNA and protein expressions of SIRT5, IDH2, MDH2 and LDHC, associated with sperm quality parameters, are downregulated after cryopreservation. In conclusion, cryopreservation induces the acetylation and deacetylation of energy metabolism-related proteins, which may contribute to the post-thawed boar sperm quality parameters.

Heparin, a class of glycosaminoglycans (GAGs), is widely used to induce sperm capacitation and fertilization. How heparin induces sperm capacitation remains unclear. Olfactory receptors (ORs) which are G protein-coupled receptors, have been proposed to be involved in sperm capacitation. However, the interaction between ORs and odor molecules and the molecular mechanism of ORs mediating sperm capacitation are still unclear. The present study aimed to explore the underlying interaction and mechanism between heparin and ORs in carrying out the boar sperm capacitation. The results showed that olfactory receptor 2C1 (OR2C1) is a compulsory unit which regulates the sperm capacitation by recognizing and binding with heparin, as determined by Dual-Glo Luciferase Assay and molecular docking. In addition, molecular dynamics (MD) simulation indicated that OR2C1 binds with heparin via a hydrophobic cavity comprises of Arg3, Ala6, Thr7, Asn171, Arg172, Arg173, and Pro287. Furthermore, we demonstrated that knocking down OR2C1 significantly inhibits sperm capacitation. In conclusion, we highlighted a novel olfactory receptor, OR2C1, in boar sperm and disclosed the potential binding of heparin to Pro287, a conserved residue in the transmembrane helices region 7 (TMH7). Our findings will benefit the further understanding of ORs involved in sperm capacitation and fertilization.

In the current study, the reversed-phased high-pressure liquid chromatography (RP-HPLC) method was proposed for the estimation of lignocaine hydrochloride (LIG), hydrocortisone (HYD) and Ketoprofen (KET) according to International Conference for Harmonization (ICH) Q2 R1 guidelines, in a gel formulation. The chromatographic evaluation was executed using Shimadzu RP-HPLC, equipped with a C8 column and detected using UV at 254 nm wavelength, using acetonitrile and buffer (50:50) as a mobile phase and diluent, at flow rate 1 mL/min and n injection volume of 20 μL. The retention time for LIG, HYD, and KET were 1.54, 2.57, and 5.78 min, correspondingly. The resultant values of analytical recovery demonstrate accuracy and precision of the method and was found specific in identification of the drugs from dosage form and marketed products. The limit of detection (LOD) for LIG, HYD, and KET were calculated to be 0.563, 0.611, and 0.669 ppm, while the limit of quantification (LOQ) was estimated almost at 1.690, 1.833, and 0.223 ppm, respectively. The AGREE software was utilized to evaluate the greenness score of the proposed method, and it was found greener in score (0.76). This study concluded that the proposed method was simple, accurate, precise, robust, economical, reproducible, and suitable for the estimation of drugs in transdermal gels.

The hydrangea ( Hydrangea macrophylla (Thunb). Ser.), an ornamental plant, has good marketing potential and is known for its capacity to change the colour of its inflorescence depending on the pH of the cultivation media. The molecular mechanisms causing these changes are still uncertain. In the present study, transcriptome and targeted metabolic profiling were used to identify molecular changes in the RNAome of hydrangea plants cultured at two different pH levels. De novo assembly yielded 186,477 unigenes. Transcriptomic datasets provided a comprehensive and systemic overview of the dynamic networks of the gene expression underlying flower colour formation in hydrangeas. Weighted analyses of gene co-expression network identified candidate genes and hub genes from the modules linked closely to the hyper accumulation of Al 3+ during different stages of flower development. F3'5'H , ANS , FLS , CHS , UA3GT , CHI , DFR , and F3H were enhanced significantly in the modules. In addition, MYB , bHLH , PAL6 , PAL9 , and WD40 were identified as hub genes. Thus, a hypothesis elucidating the colour change in the flowers of Al 3+ -treated plants was established. This study identified many potential key regulators of flower pigmentation, providing novel insights into the molecular networks in hydrangea flowers.

Oil palm ( Elaeis guineensis Jacq.) is an economically important tropical oil crop widely cultivated in tropical zones worldwide. Being a tropical crop, low-temperature stress adversely affects the oil palm. However, integrative leaf transcriptomic and proteomic analyses have not yet been conducted on an oil palm crop under cold stress. In this study, integrative omics transcriptomic and iTRAQ-based proteomic approaches were employed for three oil palm varieties, i.e., B × E (Bamenda × Ekona), O × G ( E. oleifera × Elaeis guineensis ), and T × E (Tanzania × Ekona), in response to low-temperature stress. In response to low-temperature stress at (8 °C) for 5 days, a total of 5175 up- and 2941 downregulated DEGs in BE-0_VS_BE-5, and a total of 3468 up- and 2443 downregulated DEGs for OG-0_VS_OG-5, and 3667 up- and 2151 downregulated DEGs for TE-0_VS_TE-5 were identified. iTRAQ-based proteomic analysis showed 349 up- and 657 downregulated DEPs for BE-0_VS_BE-5, 372 up- and 264 downregulated DEPs for OG-0_VS_OG-5, and 500 up- and 321 downregulated DEPs for TE-0_VS_TE-5 compared to control samples treated at 28 °C and 8 °C, respectively. The KEGG pathway correlation of oil palm has shown that the metabolic synthesis and biosynthesis of secondary metabolites pathways were significantly enriched in the transcriptome and proteome of the oil palm varieties. The correlation expression pattern revealed that TE-0_VS_TE-5 is highly expressed and BE-0_VS_BE-5 is suppressed in both the transcriptome and proteome in response to low temperature. Furthermore, numerous transcription factors (TFs) were found that may regulate cold acclimation in three oil palm varieties at low temperatures. Moreover, this study identified proteins involved in stresses (abiotic, biotic, oxidative, and heat shock), photosynthesis, and respiration in iTRAQ-based proteomic analysis of three oil palm varieties. The increased abundance of stress-responsive proteins and decreased abundance of photosynthesis-related proteins suggest that the TE variety may become cold-resistant in response to low-temperature stress. This study may provide a basis for understanding the molecular mechanism for the adaptation of oil palm varieties in response to low-temperature stress in China.

Fruit color is one of the most critical characteristics of pepper. In this study, pepper ( Capsicum baccatum L.) fruits with four trans-coloring periods were used as experimental materials to explore the color conversion mechanism of pepper fruit. By transcriptome and metabolome analysis, we identified a total of 307 flavonoid metabolites, 68 carotenoid metabolites, 29 DEGs associated with flavonoid biosynthesis, and 30 DEGs related to carotenoid biosynthesis. Through WGCNA (weighted gene co-expression network analysis) analysis, positively correlated modules with flavonoids and carotenoids were identified, and hub genes associated with flavonoid and carotenoid synthesis and transport were anticipated. We identified Pinobanksin, Naringenin Chalcone, and Naringenin as key metabolites in the flavonoid biosynthetic pathway catalyzed by the key genes chalcone synthase ( CHS CQW23_29123 , CQW23_29380 , CQW23_12748 ), cinnamic acid 4-hydroxylase ( C4H CQW23_16085 , CQW23_16084 ), cytochrome P450 ( CYP450 CQW23_19845 , CQW23_24900 ). In addition, phytoene synthase ( PSY CQW23_09483 ), phytoene dehydrogenase ( PDS CQW23_11317 ), zeta-carotene desaturase ( ZDS CQW23_19986 ), lycopene beta cyclase ( LYC CQW23_09027 ), zeaxanthin epoxidase ( ZEP CQW23_05387 ), 9-cis-epoxycarotenoid dioxygenase ( NCED CQW23_17736 ), capsanthin/capsorubin synthase ( CCS CQW23_30321 ) are key genes in the carotenoid biosynthetic pathway, catalyzing the synthesis of key metabolites such as Phytoene, Lycopene, β-carotene and ε-carotene. We also found that transcription factor families such as p450 and NBARC could play important roles in the biosynthesis of flavonoids and carotenoids in pepper fruits. These results provide new insights into the interaction mechanisms of genes and metabolites involved in the biosynthesis of flavonoids and carotenoids in pepper fruit leading to color changes in pepper fruit.

The increasing prevalence of obesity has become a demanding issue in both high-income and low-income countries. Treating obesity is challenging as the treatment options have many limitations. Recently, diet modification has been commonly applied to control or prevent obesity and its risks. In this study, we investigated novel therapeutic approaches using a combination of a potential probiotic source with prebiotics. Forty-eight adult male Sprague-Dawley rats were selected and divided into seven groups (eight rats per group). The first group was fed a high-fat diet, while the second group was a negative control. The other five groups were orally administered with a probiotic, Lactiplantibacillus plantarum ( L. plantarum ), and potential prebiotics sources (chia seeds, green tea, and chitosan) either individually or in combination for 45 days. We collected blood samples to analyze the biochemical parameters and dissected organs, including the liver, kidney, and pancreas, to evaluate obesity-related injuries. We observed a more significant decrease in the total body weight by combining these approaches than with individual agents. Moreover, treating the obese rats with this combination decreased serum catalase, superoxide dismutase, and liver malondialdehyde levels. A histopathological examination revealed a reduction in obesity-related injuries in the liver, kidney, and pancreas. Further docking studies indicated the potential role of chia seeds and green tea components in modulating obesity and its related problems. Therefore, we suggest that the daily administration of a pre- and probiotic combination may reduce obesity and its related problems.

Nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and viral hepatitis are the main causes of morbidity and mortality related to chronic liver diseases (CLDs) worldwide. New therapeutic approaches to prevent or reverse these liver disorders are thus emerging. Although their etiologies differ, these CLDs all have in common a significant dysregulation of liver metabolism that is closely linked to the perturbation of the hepatic endocannabinoid system (eCBS) and inflammatory pathways. Therefore, targeting the hepatic eCBS might have promising therapeutic potential to overcome CLDs. Experimental models of CLDs and observational studies in humans suggest that cannabis and its derivatives may exert hepatoprotective effects against CLDs through diverse pathways. However, these promising therapeutic benefits are not yet fully validated, as the few completed clinical trials on phytocannabinoids, which are thought to hold the most promising therapeutic potential (cannabidiol or tetrahydrocannabivarin), remained inconclusive. Therefore, expanding research on less studied phytocannabinoids and their derivatives, with a focus on their mode of action on liver metabolism, might provide promising advances in the development of new and original therapeutics for the management of CLDs, such as NAFLD, ALD, or even hepatitis C-induced liver disorders.

Light is the key factor affecting the synthesis of anthocyanins in pepper. In this study, pepper fruit under different light days was used as experimental material to explore the synthesis of anthocyanins in purple pepper. A total of 38 flavonoid metabolites were identified in the purple pepper germplasm HNUCA21 by liquid chromatography-tandem mass spectrometry (LC-MS/MS), of which 30 belong to anthocyanins. The detected anthocyanin with the highest content was Delphinidin-3-O-glucoside (17.13 µg/g), which reached the maximum after 168 h of light treatment. Through weighted gene co-expression network analysis (WGCNA), the brown module was identified to be related to the early synthesis of anthocyanins. This module contains many structural genes related to flavonoid synthesis, including chalcone synthase ( CHS 107871256, 107864266), chalcone isomerase ( CHI 107871144, 107852750), dihydroflavonol 4-reductase ( DFR 107860031), flavonoid 3' 5'-hydroxylase ( F3'5'H 107848667), flavonoid 3'-monooxygenase ( F3M 107862334), leucoanthocyanidin dioxygenase ( LDOX 107866341), and trans-cinnamate 4-monooxygenase ( TCM 107875406, 107875407). The module also contained some genes related to anthocyanin transport function, such as glutathione S-transferase ( GST 107861273), anthocyanidin 3-O-glucosyltransferase ( UDPGT 107861697, 107843659), and MATE (107863234, 107844661), as well as some transcription factors, such as EGL1 (107865400), basic helix-loop-helix 104 ( bHLH104 107864591), and WRKY44 (107843538, 107843524). The co-expression regulatory network indicated the involvement of CHS , DFR , CHI , and EGL1 , as well as two MATE and two WRKY 44 genes in anthocyanin synthesis. The identified genes involved in early, middle, and late light response provided a reference for the further analysis of the regulatory mechanism of anthocyanin biosynthesis in pepper.

Protoplasts, which lack cell walls, are ideal research materials for genetic engineering. They are commonly employed in fusion (they can be used for more distant somatic cell fusion to obtain somatic hybrids), genetic transformation, plant regeneration, and other applications. Cotton is grown throughout the world and is the most economically important crop globally. It is therefore critical to study successful extraction and transformation efficiency of cotton protoplasts. In the present study, a cotton callus protoplast extraction method was tested to optimize the ratio of enzymes (cellulase, pectinase, macerozyme R-10, and hemicellulase) used in the procedure. The optimized ratio significantly increased the quantity and activity of protoplasts extracted. We showed that when enzyme concentrations of 1.5% cellulase and 1.5% pectinase, and either 1.5% or 0.5% macerozyme and 0.5% hemicellulase were used, one can obtain increasingly stable protoplasts. We successfully obtained fluorescent protoplasts by transiently expressing fluorescent proteins in the isolated protoplasts. The protoplasts were determined to be suitable for use in further experimental studies. We also studied the influence of plasmid concentration and transformation time on protoplast transformation efficiency. When the plasmid concentration reaches 16 µg and the transformation time is controlled within 12-16 h, the best transformation efficiency can be obtained. In summary, this study presents efficient extraction and transformation techniques for cotton protoplasts., Competing Interests: The authors declare no conflict of interest.

Circular ribonucleic acids (circRNAs) are novel non-coding RNAs that emanate from alternative splicing of precursor mRNA in reversed order across exons. Despite the abundant presence of circRNAs in human genes and their involvement in diverse physiological processes, the functionality of most circRNAs remains a mystery. Like other non-coding RNAs, sub-cellular localization knowledge of circRNAs has the aptitude to demystify the influence of circRNAs on protein synthesis, degradation, destination, their association with different diseases, and potential for drug development. To date, wet experimental approaches are being used to detect sub-cellular locations of circular RNAs. These approaches help to elucidate the role of circRNAs as protein scaffolds, RNA-binding protein (RBP) sponges, micro-RNA (miRNA) sponges, parental gene expression modifiers, alternative splicing regulators, and transcription regulators. To complement wet-lab experiments, considering the progress made by machine learning approaches for the determination of sub-cellular localization of other non-coding RNAs, the paper in hand develops a computational framework, Circ-LocNet, to precisely detect circRNA sub-cellular localization. Circ-LocNet performs comprehensive extrinsic evaluation of 7 residue frequency-based, residue order and frequency-based, and physio-chemical property-based sequence descriptors using the five most widely used machine learning classifiers. Further, it explores the performance impact of K-order sequence descriptor fusion where it ensembles similar as well dissimilar genres of statistical representation learning approaches to reap the combined benefits. Considering the diversity of statistical representation learning schemes, it assesses the performance of second-order, third-order, and going all the way up to seventh-order sequence descriptor fusion. A comprehensive empirical evaluation of Circ-LocNet over a newly developed benchmark dataset using different settings reveals that standalone residue frequency-based sequence descriptors and tree-based classifiers are more suitable to predict sub-cellular localization of circular RNAs. Further, K-order heterogeneous sequence descriptors fusion in combination with tree-based classifiers most accurately predict sub-cellular localization of circular RNAs. We anticipate this study will act as a rich baseline and push the development of robust computational methodologies for the accurate sub-cellular localization determination of novel circRNAs.

Gold nanoparticles (AuNPs) are becoming increasingly popular as drug carriers due to their unique properties such as size tenability, multivalency, low toxicity and biocompatibility. AuNPs have physical features that distinguish them from bulk materials, small molecules and other nanoscale particles. Their unique combination of characteristics is just now being fully realized in various biomedical applications. In this review, we focus on the research accomplishments and new opportunities in this field, and we describe the rising developments in the use of monodisperse AuNPs for diagnostic and therapeutic applications. This study addresses the key principles and the most recent published data, focusing on monodisperse AuNP synthesis, surface modifications, and future theranostic applications. Moving forward, we also consider the possible development of functionalized monodisperse AuNPs for theranostic applications based on these efforts. We anticipate that as research advances, flexible AuNPs will become a crucial platform for medical applications.

Cold stress, triggered by particularly low temperatures, is one of the most severe forms of abiotic stress in pepper plants and a major constraint to the global pepper industry, threatening crop production and food security. To acclimatize to extreme conditions, the plant undergoes numerous modifications, including genetic and metabolic modulations. A thorough study of both the genetic and metabolic alterations of plants in response to cold stress is vital to understanding and developing the cold stress resistance mechanism. This study implemented transcriptome and metabolome analyses to evaluate the cold stress response in cold-tolerant and cold-sensitive pepper species. The weighted gene co-expression network revealed three significant modules related to cold stress tolerance in Capsicum pubescens . We identified 17 commonly enriched genes among both species at different time points in 10 different comparisons, including the AP2 transcription factor, LRR receptor-like serine, hypersensitivity-related 4-like protein, and uncharacterized novel.295 and novel.6172 genes. A pathway enrichment analysis indicated that these DEGs were mainly associated with the MAPK signaling pathway, hormone signaling pathway, and primary and secondary metabolism. Additionally, 21 significantly differentially accumulated metabolites (DAMs) were identified in both species after 6 h of cold stress. A transcriptome and metabolome integrated analysis revealed that 54 genes correlated with metabolites enriched in five different pathways. Most genes and metabolites involved in carbohydrate metabolism, the TCA cycle, and flavonoid biosynthesis pathways were upregulated in cold-tolerant plants under cold stress. Together, the results of this study provide a comprehensive gene regulatory and metabolic network in response to cold stress and identified some key genes and metabolic pathways involved in pepper cold tolerance. This study lays a foundation for the functional characterization and development of pepper cultivars with improved cold tolerance.

In the present study, the effects of foliar application of salicylic acid (100 μM), cerium oxide (50 mg L -1 ), and cerium oxide:salicylic acid nanoparticles (CeO 2 : SA-nanoparticles, 50 mg L -1 + 100 μM) on the growth and physiological responses of purslane ( Portulaca oleracea L.) were examined in non-saline and saline conditions (50 and 100 mM NaCl salinity). Foliar applications mitigated salinity-induced adverse effects, and the highest plant height and N, P, Mg, and Mn content were recorded in the variant with non-saline × foliar use of CeO 2 : SA-nanoparticles. The highest values of fresh and dry weight were noted in the treatment with no-salinity × foliar use of CeO 2 :SA-nanoparticles. The highest number of sub-branches was observed in the foliar treatments with CeO 2 -nanoparticles and CeO 2 :SA-nanoparticles without salinity stress, while the lowest number was noted in the 100 mM NaCl treatment. Moreover, the foliar application of CeO 2 :SA-nanoparticles and cerium-oxide nanoparticles improved the total soluble solid content, K, Fe, Zn, Ca, chlorophyll a, and oil yield in the plants. The salinity of 0 and 50 mM increased the K content, 1000-seed weight, total soluble solid content, and chlorophyll b content. The use of 100 mM NaCl with no-foliar spray increased the malondialdehyde, Na, and H 2 O 2 content and the Na + /K + ratio. No-salinity and 50 mM NaCl × CeO 2 : SA-nanoparticle interactions improved the anthocyanin content in plants. The phenolic content was influenced by NaCl 100 and the foliar use of CeO 2 :SA-nanoparticles. The study revealed that the foliar treatment with CeO 2 :SA-nanoparticles alleviated the side effects of salinity by improving the physiological responses and growth-related traits of purslane plants.

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge, as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and the encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer, presents novel nanomedicine therapeutics aimed at improving the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for the clinical application of nanomedicine in the management of LC resistance.

Umami ingredients have been identified as important factors in food seasoning and production. Traditional experimental methods for characterizing peptides exhibiting umami sensory properties (umami peptides) are time-consuming, laborious, and costly. As a result, it is preferable to develop computational tools for the large-scale identification of available sequences in order to identify novel peptides with umami sensory properties. Although a computational tool has been developed for this purpose, its predictive performance is still insufficient. In this study, we use a feature representation learning approach to create a novel machine-learning meta-predictor called UMPred-FRL for improved umami peptide identification. We combined six well-known machine learning algorithms (extremely randomized trees, k-nearest neighbor, logistic regression, partial least squares, random forest, and support vector machine) with seven different feature encodings (amino acid composition, amphiphilic pseudo-amino acid composition, dipeptide composition, composition-transition-distribution, and pseudo-amino acid composition) to develop the final meta-predictor. Extensive experimental results demonstrated that UMPred-FRL was effective and achieved more accurate performance on the benchmark dataset compared to its baseline models, and consistently outperformed the existing method on the independent test dataset. Finally, to aid in the high-throughput identification of umami peptides, the UMPred-FRL web server was established and made freely available online. It is expected that UMPred-FRL will be a powerful tool for the cost-effective large-scale screening of candidate peptides with potential umami sensory properties.

Hashimoto thyroiditis (HT) is a common autoimmune disorder with a strong genetic background. Several genetic factors have been suggested, yet numerous genetic contributors remain to be fully understood in HT pathogenesis. MicroRNAs (miRs) are gene expression regulators critically involved in biological processes, of which polymorphisms can alter their function, leading to pathologic conditions, including autoimmune diseases. We examined whether miR-499 rs3746444 polymorphism is associated with susceptibility to HT in an Iranian subpopulation. Furthermore, we investigated the potential interacting regulatory network of the miR-499. This case-control study included 150 HT patients and 152 healthy subjects. Genotyping of rs3746444 was performed by the PCR-RFLP method. Also, target genomic sites of the polymorphism were predicted using bioinformatics. Our results showed that miR-499 rs3746444 was positively associated with HT risk in heterozygous (OR = 3.32, 95%CI = 2.00-5.53, p < 0.001, CT vs. TT), homozygous (OR = 2.81, 95%CI = 1.30-6.10, p = 0.014, CC vs. TT), dominant (OR = 3.22, 95%CI = 1.97-5.25, p < 0.001, CT + CC vs. TT), overdominant (OR = 2.57, 95%CI = 1.62-4.09, p < 0.001, CC + TT vs. CT), and allelic (OR = 1.92, 95%CI = 1.37-2.69, p < 0.001, C vs. T) models. Mapping predicted target genes of miR-499 on tissue-specific-, co-expression-, and miR-TF networks indicated that main hub-driver nodes are implicated in regulating immune system functions, including immunorecognition and complement activity. We demonstrated that miR-499 rs3746444 is linked to HT susceptibility in our population. However, predicted regulatory networks revealed that this polymorphism is contributing to the regulation of immune system pathways.

Accurate identification of bitter peptides is of great importance for better understanding their biochemical and biophysical properties. To date, machine learning-based methods have become effective approaches for providing a good avenue for identifying potential bitter peptides from large-scale protein datasets. Although few machine learning-based predictors have been developed for identifying the bitterness of peptides, their prediction performances could be improved. In this study, we developed a new predictor (named iBitter-Fuse) for achieving more accurate identification of bitter peptides. In the proposed iBitter-Fuse, we have integrated a variety of feature encoding schemes for providing sufficient information from different aspects, namely consisting of compositional information and physicochemical properties. To enhance the predictive performance, the customized genetic algorithm utilizing self-assessment-report (GA-SAR) was employed for identifying informative features followed by inputting optimal ones into a support vector machine (SVM)-based classifier for developing the final model (iBitter-Fuse). Benchmarking experiments based on both 10-fold cross-validation and independent tests indicated that the iBitter-Fuse was able to achieve more accurate performance as compared to state-of-the-art methods. To facilitate the high-throughput identification of bitter peptides, the iBitter-Fuse web server was established and made freely available online. It is anticipated that the iBitter-Fuse will be a useful tool for aiding the discovery and de novo design of bitter peptides.

Age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is a degenerative disease of the macula, where retinal pigment epithelium (RPE) cells are damaged in the early stages of the disease, and chronic inflammatory processes may be involved. Besides aging and lifestyle factors as drivers of AMD, a strong genetic association to AMD is found in genes of the complement system, with a single polymorphism in the complement factor H gene ( CFH ), accounting for the majority of AMD risk. However, the exact mechanism of CFH dysregulation confers such a great risk for AMD and its role in RPE cell homeostasis is unclear. To explore the role of endogenous CFH locally in RPE cells, we silenced CFH in human hTERT-RPE1 cells. We demonstrate that endogenously expressed CFH in RPE cells modulates inflammatory cytokine production and complement regulation, independent of external complement sources, or stressors. We show that loss of the factor H protein (FH) results in increased levels of inflammatory mediators (e.g., IL-6, IL-8, GM-CSF) and altered levels of complement proteins (e.g., C3, CFB upregulation, and C5 downregulation) that are known to play a role in AMD. Moreover, our results identify the NF-κB pathway as the major pathway involved in regulating these inflammatory and complement factors. Our findings suggest that in RPE cells, FH and the NF-κB pathway work in synergy to maintain inflammatory and complement balance, and in case either one of them is dysregulated, the RPE microenvironment changes towards a proinflammatory AMD-like phenotype.

Apart from protein-coding Ribonucleic acids (RNAs), there exists a variety of non-coding RNAs (ncRNAs) which regulate complex cellular and molecular processes. High-throughput sequencing technologies and bioinformatics approaches have largely promoted the exploration of ncRNAs which revealed their crucial roles in gene regulation, miRNA binding, protein interactions, and splicing. Furthermore, ncRNAs are involved in the development of complicated diseases like cancer. Categorization of ncRNAs is essential to understand the mechanisms of diseases and to develop effective treatments. Sub-cellular localization information of ncRNAs demystifies diverse functionalities of ncRNAs. To date, several computational methodologies have been proposed to precisely identify the class as well as sub-cellular localization patterns of RNAs). This paper discusses different types of ncRNAs, reviews computational approaches proposed in the last 10 years to distinguish coding-RNA from ncRNA, to identify sub-types of ncRNAs such as piwi-associated RNA, micro RNA, long ncRNA, and circular RNA, and to determine sub-cellular localization of distinct ncRNAs and RNAs. Furthermore, it summarizes diverse ncRNA classification and sub-cellular localization determination datasets along with benchmark performance to aid the development and evaluation of novel computational methodologies. It identifies research gaps, heterogeneity, and challenges in the development of computational approaches for RNA sequence analysis. We consider that our expert analysis will assist Artificial Intelligence researchers with knowing state-of-the-art performance, model selection for various tasks on one platform, dominantly used sequence descriptors, neural architectures, and interpreting inter-species and intra-species performance deviation.

Due to similar coordination chemistry of palladium and platinum, a large number of palladium compounds as well have been investigated for their anticancer activity. In the present study, we describe synthesis, characterization, and anticancer activity of palladium complex [Bis(1,8-quinolato)palladium (II)], coded as NH3 against seven different cancer cell lines. NH3 is found to have higher antitumor activity than cisplatin against both parent ovarian A2780 cell line and cisplatin-resistant cell lines. Also, NH3 has the lower IC 50 value in HT-29 colorectal cancer cell line. The higher antitumor activity of NH3 is due to the presence of bulky 8-Hydroxyquinoline ligand, thus reducing its reactivity. Proteomic study has identified significantly expressed proteins which have been validated through bioinformatics. NH3 has been found to be less toxic than cisplatin at 2.5 mg/kg and 5 mg/kg dosages on mice models. Binary combinations of NH3 with curcumin and epigallocatechin gallate (EGCG) have demonstrated dose and sequence-dependent synergism in ovarian and colorectal cancer models. All of the preclinical studies indicate promising therapeutic potential of NH3 [Bis(1,8-quinolato)palladium (II)] as an anticancer drug.

The use of experimental relations to approximate the efficient thermophysical properties of a nanofluid (NF) with Cu nanoparticles (NPs) and hybrid nanofluid (HNF) with Cu-SWCNT NPs and subsequently model the two-dimensional pulsatile Casson fluid flow under the impact of the magnetic field and thermal radiation is a novelty of the current study. Heat and mass transfer analysis of the pulsatile flow of non-Newtonian Casson HNF via a Darcy-Forchheimer porous channel with compliant walls is presented. Such a problem offers a prospective model to study the blood flow via stenosed arteries. A finite-difference flow solver is used to numerically solve the system obtained using the vorticity stream function formulation on the time-dependent governing equations. The behavior of Cu-based NF and Cu-SWCNT-based HNF on the wall shear stress (WSS), velocity, temperature, and concentration profiles are analyzed graphically. The influence of the Casson parameter, radiation parameter, Hartmann number, Darcy number, Soret number, Reynolds number, Strouhal number, and Peclet number on the flow profiles are analyzed. Furthermore, the influence of the flow parameters on the non-dimensional numbers such as the skin friction coefficient, Nusselt number, and Sherwood number is also discussed. These quantities escalate as the Reynolds number is enhanced and reduce by escalating the porosity parameter. The Peclet number shows a high impact on the microorganism's density in a blood NF. The HNF has been shown to have superior thermal properties to the traditional one. These results could help in devising hydraulic treatments for blood flow in highly stenosed arteries, biomechanical system design, and industrial plants in which flow pulsation is essential.

Nitrotyrosine, which is generated by numerous reactive nitrogen species, is a type of protein post-translational modification. Identification of site-specific nitration modification on tyrosine is a prerequisite to understanding the molecular function of nitrated proteins. Thanks to the progress of machine learning, computational prediction can play a vital role before the biological experimentation. Herein, we developed a computational predictor PredNTS by integrating multiple sequence features including K-mer, composition of k-spaced amino acid pairs (CKSAAP), AAindex, and binary encoding schemes. The important features were selected by the recursive feature elimination approach using a random forest classifier. Finally, we linearly combined the successive random forest (RF) probability scores generated by the different, single encoding-employing RF models. The resultant PredNTS predictor achieved an area under a curve (AUC) of 0.910 using five-fold cross validation. It outperformed the existing predictors on a comprehensive and independent dataset. Furthermore, we investigated several machine learning algorithms to demonstrate the superiority of the employed RF algorithm. The PredNTS is a useful computational resource for the prediction of nitrotyrosine sites. The web-application with the curated datasets of the PredNTS is publicly available.

Organic cation transporters (OCT) 1, 2 and 3 and novel organic cation transporters (OCTN) 1 and 2 of the solute carrier 22 (SLC22) family are involved in the cellular transport of endogenous compounds such as neurotransmitters, l-carnitine and ergothioneine. OCT/Ns have also been implicated in the transport of xenobiotics across various biological barriers, for example biguanides and histamine receptor antagonists. In addition, several drugs used in the treatment of respiratory disorders are cations at physiological pH and potential substrates of OCT/Ns. OCT/Ns may also be associated with the development of chronic lung diseases such as allergic asthma and chronic obstructive pulmonary disease (COPD) and, thus, are possible new drug targets. As part of the Special Issue "Physiology, Biochemistry and Pharmacology of Transporters for Organic Cations", this review provides an overview of recent findings on the (patho)physiological and pharmacological functions of organic cation transporters in the lung.

Allotetraploid cotton ( Gossypium hirsutum and Gossypium barbadense ) are cultivated worldwide for its white fiber. For centuries, conventional breeding approaches increase cotton yield at the cost of extensive erosion of natural genetic variability. Sea Island cotton ( G. barbadense ) is known for its superior fiber quality, but show poor adaptability as compared to Upland cotton. Here, in this study, we use ethylmethanesulfonate (EMS) as a mutagenic agent to induce genome-wide point mutations to improve the current germplasm resources of Sea Island cotton and develop diverse breeding lines with improved adaptability and excellent economic traits. We determined the optimal EMS experimental procedure suitable for construction of cotton mutant library. At M 6 generation, mutant library comprised of lines with distinguished phenotypes of the plant architecture, leaf, flower, boll, and fiber. Genome-wide analysis of SNP distribution and density in yellow leaf mutant reflected the better quality of mutant library. Reduced photosynthetic efficiency and transmission electron microscopy of yellow leaf mutants revealed the effect of induced mutations at physiological and cellular level. Our mutant collection will serve as the valuable resource for basic research on cotton functional genomics, as well as cotton breeding.

Reactive oxygen species are a byproduct of aerobic metabolic processes but are also produced by plants in defense against pathogens. In addition, they can function as signaling molecules that control various aspects of plant life, ranging from developmental processes to responses to abiotic and biotic stimuli. In plants, reactive oxygen species can be produced by respiratory burst oxidase homologues. Arabidopsis contains 10 genes for respiratory burst oxidase homologues that are involved in different aspects of plant life. Plant pathogenic cyst nematodes such as Heterodera schachtii induce a syncytium in the roots of host plants that becomes a feeding site which supplies nutrients throughout the life of the nematode. In line with this function, the transcriptome of the syncytium shows drastic changes. One of the genes that is most strongly downregulated in syncytia codes for respiratory burst oxidase homologue B. This gene is root-specific and we confirm here the downregulation in nematode feeding sites with a promoter::GUS (β-glucuronidase) line. Overexpression of this gene resulted in enhanced resistance against nematodes but also against leaf-infecting pathogens. Thus, respiratory burst oxidase homologue B has a role in resistance. The function of this gene is in contrast to respiratory burst oxidase homologues D and F, which have been found to be needed for full susceptibility of Arabidopsis to H. schachtii. However, our bioinformatic analysis did not find differences between these proteins that could account for the opposed function in the interaction with nematodes.

Arabidopsis contains 34 genes for glycosylphosphatidylinositol (GPI)-anchored LTPg proteins. A motif analysis has placed these into four groups. With one exception, all are produced with a signal peptide and are most likely attached to the cell membrane via the GPI anchor. Several of the LTPg genes across the four groups are downregulated in syncytia induced by the beet cyst nematode Heterodera schachtii . We have here studied At3g22600 encoding LTPg5, which is the most strongly downregulated LTPg gene. It is mainly expressed in roots, and a promoter::GUS line was used to confirm the downregulation in syncytia and also showed downregulation in galls of the root knot nematode Meloidogyne incognita . In contrast, infection with bacteria ( Pseudomonas syringae ) and fungi ( Botrytis cinerea ) led to the induction of the gene in leaves. This diverse regulation of LTPg5 indicated a role in resistance, which we confirmed with overexpression lines and a T-DNA mutant. The overexpression lines were more resistant to both nematode species and to P. syringae and B. cinerea , while a knock-out mutant was more susceptible to H. schachtii and P. syringae . Thus, LTPg5 encoded by At3g22600 is part of the Arabidopsis resistance mechanism against pathogens. LTPg5 has probably no direct antimicrobial activity but could perhaps act by associating with a receptor-like kinase, leading to the induction of defense genes such as PR1 .

The human zinc transporter 8 (hZnT8) plays important roles in the storage of insulin in the secretory vesicles of pancreatic β cells. hZnT8 consists of a transmembrane domain, with its N- and C-termini protruding into the cytoplasm. Interestingly, the exchange of arginine to tryptophan at position 325 in the C-terminal domain (CTD) increases the risk of developing type 2 diabetes mellitus (T2D). In the present study, the CTDs of hZnT8 (the wild-type (WT) and its disease risk variant (R325W)) were expressed, purified, and characterized in their native forms by biophysical techniques. The data reveal that the CTDs form tetramers which are stabilized by zinc binding, and exhibit negligible differences in their secondary structure content and zinc-binding affinities in solution. These findings provide the basis for conducting further structural studies aimed at unravelling the molecular mechanism underlying the increased susceptibility to develop T2D, which is modulated by the disease risk variant.

Proximal tubular epithelial cells (PTEC) are key players in the progression of kidney diseases. PTEC studies to date have primarily used mouse models and transformed human PTEC lines. However, the translatability of these models to human kidney disease has been questioned. In this study, we investigated the phenotypic and functional response of human primary PTEC to oxidative stress, an established driver of kidney disease. Furthermore, we examined the functional contribution of the underlying histopathology of the cortical tissue used to generate our PTEC. We demonstrated that human primary PTEC from both histologically 'normal' and 'diseased' cortical tissue responded to H 2 O 2 -induced oxidative stress with significantly elevated mitochondrial superoxide levels, DNA damage, and significantly decreased proliferation. The functional response of 'normal' PTEC to oxidative stress mirrored the reported pathogenesis of human kidney disease, with significantly attenuated mitochondrial function and increased cell death. In contrast, 'diseased' PTEC were functionally resistant to oxidative stress, with maintenance of mitochondrial function and cell viability. This selective survival of 'diseased' PTEC under oxidizing conditions is reminiscent of the in vivo persistence of maladaptive PTEC following kidney injury. We are now exploring the impact that these differential PTEC responses have in the therapeutic targeting of oxidative stress pathways.

Calcium-dependent protein kinase (CPKs) is a key player in the calcium signaling pathway to decode calcium signals into various physiological responses. cDNA sequences of 9 Zm CPK genes were successfully cloned from all four phylogenetic groups in maize. qRT-PCR analysis showed the expression variation of these selected genes under abscisic acid (ABA) and calcium chloride (CaCl 2 ) treatment. Due to the presence of N-myristoylation/palmitoylation sites, the selected Zm CPK members were localized in a plasma membrane. To clarify whether Zm CPK, a key player in calcium signaling, interacts with key players of ABA, protein phosphatase 2Cs (PP2Cs) and the SNF1-related protein kinase 2s (SnRK2s) and mitogen-activated protein kinase (MAPK) signaling pathways in maize, we examined the interaction between 9 CPKs, 8 PP2Cs, 5 SnRKs, and 20 members of the MPK family in maize by using yeast two-hybrid assay. Our results showed that three Zm CPKs interact with three different members of Zm SnRKs while four Zm CPK members had a positive interaction with 13 members of Zm MPKs in different combinations. These four Zm CPK proteins are from three different groups in maize. These findings of physical interactions between Zm CPKs, Zm SnRKs, and Zm MPKs suggested that these signaling pathways do not only have indirect influence but also have direct crosstalk that may involve the defense mechanism in maize. The present study may improve the understanding of signal transduction in plants.

We employed dielectrophoresis to a yeast cell suspension containing amyloid-beta proteins (Aβ) in a microfluidic environment. The Aβ was separated from the cells and characterized using the gradual dissolution of Aβ as a function of the applied dielectrophoretic parameters. We established the gradual dissolution of Aβ under specific dielectrophoretic parameters. Further, Aβ in the fibril form at the tip of the electrode dissolved at high frequency. This was perhaps due to the conductivity of the suspending medium changing according to the frequency, which resulted in a higher temperature at the tips of the electrodes, and consequently in the breakdown of the hydrogen bonds. However, those shaped as spheroidal monomers experienced a delay in the Aβ fibril transformation process. Yeast cells exposed to relatively low temperatures at the base of the electrode did not experience a positive or negative change in viability. The DEP microfluidic platform incorporating the integrated microtip electrode array was able to selectively manipulate the yeast cells and dissolve the Aβ to a controlled extent. We demonstrate suitable dielectrophoretic parameters to induce such manipulation, which is highly relevant for Aβ-related colloidal microfluidic research and could be applied to Alzheimer's research in the future.

The process of coagulation and precipitation affect the fate and mobility of antimony (Sb) species in drinking water. Moreover, the solubility and physico-chemical properties of the precipitates may be affected by the media chemistry. Accordingly, the present study aimed to investigate the removal of Sb(III, V) species by ferric chloride coagulation under various water chemistry influences with a particular focus on the role of the properties of the precipitates. The results indicated that the amount of Sb(III) removed increased with increasing solution pH, showing the insignificant effects of the hydrodynamic diameter (HDD) and ζ-potential of the precipitates. However, no Sb(V) removal occurred at alkaline pH values, while a highly negative ζ-potential and the complete dissolution of precipitates were observed in the aqueous solution. The solution pH was also useful in determining the dominant coagulation mechanisms, such as co-precipitation and adsorption. The Fe solubility substantially affects the Sb removal at a certain pH range, while the HDD of the precipitates plays an insignificant role in Sb removal. The presence of divalent cations brings the ζ-potential of the precipitates close to point of zero charge (pzc), thus enhancing the Sb(V) removal at alkaline pH conditions. Pronounced adverse effects of humic acid were observed on Sb removal, ζ-potential and HDD of the precipitates. In general, this study may provide critical information to a wide group of researchers dealing with environmental protection from heavy metal pollution.

Besides its key role in neural development, brain-derived neurotrophic factor (BDNF) is important for long-term potentiation and neurogenesis, which makes it a critical factor in learning and memory. Due to the important role of BDNF in synaptic function and plasticity, an in-house epigenetic library was screened against human neural progenitor cells (HNPCs) and WS1 human skin fibroblast cells using Cell-to-Ct assay kit to identify the small compounds capable of modulating the BDNF expression. In addition to two well-known hydroxamic acid-based histone deacetylase inhibitors (hb-HDACis), SAHA and TSA, several structurally similar HDAC inhibitors including SB-939, PCI-24781 and JNJ-26481585 with even higher impact on BDNF expression, were discovered in this study. Furthermore, by using well-developed immunohistochemistry assays, the selected compounds were also proved to have neurogenic potential improving the neurite outgrowth in HNPCs-derived neurons. In conclusion, we proved the neurogenic potential of several hb-HDACis, alongside their ability to enhance BDNF expression, which by modulating the neurogenesis and/or compensating for neuronal loss, could be propitious for treatment of neurological disorders.

Grain quality improvement is a key target for rice breeders, along with yield. It is a multigenic trait that is simultaneously influenced by many factors. Over the past few decades, breeding for semi-dwarf cultivars and hybrids has significantly contributed to the attainment of high yield demands but reduced grain quality, which thus needs the attention of researchers. The availability of rice genome sequences has facilitated gene discovery, targeted mutagenesis, and revealed functional aspects of rice grain quality attributes. Some success has been achieved through the application of molecular markers to understand the genetic mechanisms for better rice grain quality; however, researchers have opted for novel strategies. Genomic alteration employing genome editing technologies (GETs) like clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) for reverse genetics has opened new avenues of research in the life sciences, including for rice grain quality improvement. Currently, CRISPR/Cas9 technology is widely used by researchers for genome editing to achieve the desired biological objectives, because of its simple targeting. Over the past few years many genes that are related to various aspects of rice grain quality have been successfully edited via CRISPR/Cas9 technology. Interestingly, studies on functional genomics at larger scales have become possible because of the availability of GETs. In this review, we discuss the progress made in rice by employing the CRISPR/Cas9 editing system and its eminent applications. We also elaborate possible future avenues of research with this system, and our understanding regarding the biological mechanism of rice grain quality improvement.

Cereal cyst nematodes (CCNs) are among the most important nematode pests that limit production of small grain cereals like wheat and barley. These nematodes alone are estimated to reduce production of crops by 10% globally. This necessitates a huge enhancement of nematode resistance in cereal crops against CCNs. Nematode resistance in wheat and barley in combination with higher grain yields has been a preferential research area for cereal nematologists. This usually involved the targeted genetic exploitations through natural means of classical selection breeding of resistant genotypes and finding quantitative trait luci (QTLs) associated with resistance genes. These improvements were based on available genetic diversity among the crop plants. Recently, genome-wide association studies have widely been exploited to associate nematode resistance or susceptibility with particular regions of the genome. Use of biotechnological tools through the application of various transgenic strategies for enhancement of nematode resistance in various crop plants including wheat and barley had also been an important area of research. These modern approaches primarily include the use of gene silencing, exploitation of nematode effector genes, proteinase inhibitors, chemodisruptive peptides and a combination of one or more of these approaches. Furthermore, the perspective genome editing technologies including CRISPR-Cas9 could also be helpful for improving CCN resistance in wheat and barley. The information provided in this review will be helpful to enhance resistance against CCNs and will attract the attention of the scientific community towards this neglected area., Competing Interests: The authors declare no conflict of interest.

A new series of 1,3,4-oxadiazoles derivatives was synthesized, characterized, and evaluated for their in vitro and in vivo anti-thrombotic activity. Compounds ( 3a ⁻ 3i ) exhibited significant clot lysis with respect to reference drug streptokinase (30,000 IU), and enhanced clotting time (CT) values (130⁻342 s) than heparin (110 s). High affinity towards 1NFY with greater docking score was observed for the compounds ( 3a , 3i , 3e , 3d , and 3h ) than the control ligand RPR200095. In addition, impressive inhibitory potential against factor Xa (F-Xa) was observed with higher docking scores (5612⁻6270) with Atomic Contact Energy (ACE) values (-189.68 to -352.28 kcal/mol) than the control ligand RPR200095 (Docking score 5192; ACE -197.81 kcal/mol). In vitro, in vivo, and in silico results proposed that these newly synthesized compounds might be used as anticoagulant agents.

To successfully invade and infect their host plants, plant parasitic nematodes (PPNs) need to evolve molecular mechanisms to overcome the defense responses from the plants. Nematode-associated molecular patterns (NAMPs), including ascarosides and certain proteins, while instrumental in enabling the infection, can be perceived by the host plants, which then initiate a signaling cascade leading to the induction of basal defense responses. To combat host resistance, some nematodes can inject effectors into the cells of susceptible hosts to reprogram the basal resistance signaling and also modulate the hosts' gene expression patterns to facilitate the establishment of nematode feeding sites (NFSs). In this review, we summarized all the known signaling pathways involved in plant⁻nematode interactions. Specifically, we placed particular focus on the effector proteins from PPNs that mimic the signaling of the defense responses in host plants. Furthermore, we gave an updated overview of the regulation by PPNs of different host defense pathways such as salicylic acid (SA)/jasmonic acid (JA), auxin, and cytokinin and reactive oxygen species (ROS) signaling to facilitate their parasitic successes in plants. This review will enhance the understanding of the molecular signaling pathways involved in both compatible and incompatible plant⁻nematode interactions.