Splice-switching antisense oligonucleotide controlling tumor suppressor REST is a novel therapeutic medicine for neuroendocrine cancer.

RNA splicing regulation has revolutionized the treatment of challenging diseases. Neuroendocrine cancers, including small cell lung cancer (SCLC) and neuroendocrine prostate cancer (PCa), are highly aggressive, with metastatic neuroendocrine phenotypes, leading to poor patient outcomes. We investigated amido-bridged nucleic acid (AmNA)-based splice-switching oligonucleotides (SSOs) targeting RE1-silencing transcription factor (REST) splicing as a novel therapy. We designed AmNA-based SSOs to alter REST splicing. Tumor xenografts were generated by subcutaneously implanting SCLC or PCa cells into mice. SSOs or saline were intraperitoneally administered and tumor growth was monitored. Blood samples were collected from mice after SSO administration, and serum alanine aminotransferase and aspartate aminotransferase levels were measured to assess hepatotoxicity using a biochemical analyser. In vitro, REST_SSO reduced cancer cell viability. In a tumor xenograft model, it exhibited significant antitumor effects. It repressed REST-controlled RE1-harboring genes and upregulated miR-4516, an SCLC biomarker. Our findings suggest that REST_SSO suppresses tumorigenesis in neuroendocrine cancers by restoring REST function. This novel therapeutic approach holds promise for intractable neuroendocrine cancers such as SCLC and neuroendocrine PCa.

Synthesis and Properties of α-Phosphate-Modified Nucleoside Triphosphates.

This review article is focused on the progress made in the synthesis of 5'-α-P-modified nucleoside triphosphates (α-phosphate mimetics). A variety of α-P-modified nucleoside triphosphates (NTPαXYs, Y = O, S; X = S, Se, BH3, alkyl, amine, N-alkyl, imido, or others) have been developed. There is a unique class of nucleoside triphosphate analogs with different properties. The main chemical approaches to the synthesis of NTPαXYs are analyzed and systematized here. Using the data presented here on the diversity of NTPαXYs and their synthesis protocols, it is possible to select an appropriate method for obtaining a desired α-phosphate mimetic. Triphosphates' substrate properties toward nucleic acid metabolism enzymes are highlighted too. We reviewed some of the most prominent applications of NTPαXYs including the use of modified dNTPs in studies on mechanisms of action of polymerases or in systematic evolution of ligands by exponential enrichment (SELEX). The presence of heteroatoms such as sulfur, selenium, or boron in α-phosphate makes modified triphosphates nuclease resistant. The most distinctive feature of NTPαXYs is that they can be recognized by polymerases. As a result, S-, Se-, or BH3-modified phosphate residues can be incorporated into DNA or RNA. This property has made NTPαXYs a multifunctional tool in molecular biology. This review will be of interest to synthetic chemists, biochemists, biotechnologists, or biologists engaged in basic or applied research.

Construction of a T m-value prediction model and molecular dynamics study of AmNA-containing gapmer antisense oligonucleotide.

RNase H-dependent antisense oligonucleotides (gapmer ASOs) represent a class of nucleic acid therapeutics that bind to target RNA to facilitate RNase H-mediated RNA cleavage, thereby regulating the expression of disease-associated proteins. Integrating artificial nucleic acids into gapmer ASOs enhances their therapeutic efficacy. Among these, amido-bridged nucleic acid (AmNA) stands out for its potential to confer high affinity and stability to ASOs. However, a significant challenge in the design of gapmer ASOs incorporating artificial nucleic acids, such as AmNA, is the accurate prediction of their melting temperature (T m ) values. The T m is a critical parameter for designing effective gapmer ASOs to ensure proper functioning. However, predicting accurate T m values for oligonucleotides containing artificial nucleic acids remains problematic. We developed a T m prediction model using a library of AmNA-containing ASOs to address this issue. We measured the T m values of 157 oligonucleotides through differential scanning calorimetry, enabling the construction of an accurate prediction model. Additionally, molecular dynamics simulations were used to elucidate the molecular mechanisms by which AmNA modifications elevate T m , thereby informing the design strategies of gapmer ASOs.

Chirality Sensing of Amino Acid Esters by S-2-Methylbutanamido-Substituted m-Phthalic Diamide-Linked Zinc Bisporphyrinate.

To understand the role of an additional coordination site in the linker in chirality sensing, we designed and synthesized an S-2-methylbutanamido-substituted m-phthalic diamide-linked zinc bisporphyrinate, [Zn2(S-MAABis)] and investigated its ability to sense the chirality of amino acid esters. The 1H NMR spectra and the crystal structure showed that the amido oxygen adjacent to the chiral carbon was coordinated with zinc. NMR and UV-vis titration showed that the binding of [Zn2(S-MAABis)] to amino acid esters occurred via two equilibria, forming 1:1 and 1:2 host-guest complexes. The CD spectra suggested that [Zn2(S-MAABis)] can effectively recognize the absolute configuration of amino acid esters. The sign of the CD spectra remained unchanged during the titration, indicating that the corresponding 1:1 and 1:2 host-guest complexes had the same chirality. This is different from previously studied amino-substituted m-phthalic diamide-linked zinc bisporphyrinate [Zn2(AmBis)], which showed chirality inversion during titration. Theoretical calculations indicated that the additional coordination sites (amido or amino) in the 1:1 host-guest complexes played different roles, leading to differences in chirality. Our studies suggest that the introduction of a coordination site can influence the chirality transfer process, but the results of chirality transfers are dependent on the specific binding modes.

A stain with all the fixing's - Enhancement of fingermarks in blood using a combined fixative and aqueous protein stain.

The use of protein stains to enhance fingermark ridge detail in blood is a common technique used by forensic practitioners around the world. Amido Black is one of the most favoured protein stains due to its strong staining ability. The most common formulation of Amido Black is methanol based, with an ability to simultaneously fix and stain the blood impression, however methanol is toxic and can disrupt some surfaces, potentially compromising fingermark detail. If the surface is suspected of being a material that is impacted by methanol, there is an alternative aqueous formulation, which requires a fixative step to set the blood prior to staining so as not to wash away potential ridge detail. The multi-step process of aqueous protein stains is tedious and numerous studies have been conducted to improve the formula to achieve a combined fixing/staining solution that performs like the methanolic reagent. A combined fixative and stain formulation of aqueous based Amido Black was compared to a multi-step formulation with a separate sulfosalicylic acid fixative. Of the 243 split fingermark impressions analysed the majority (63.5 %) showed no preference to either treatment, with a marginally greater proportion of the remaining marks slightly favouring the combined fixative and stain formulation. Given that the new combined formulation performed broadly similarly to the existing multi step formulation, the potential time savings of this simpler approach may be beneficial to implement into operational use.

Tuning Energetics of 2 e-/2H+ PCET Properties with Model Ru-bisamido Complexes.

Most redox processes that break/form bonds involve net 2e- changes, and many are coupled to protons. Yet most proton-coupled electron transfer (PCET) studies focus on 1e-/1H+ reactions. Reported here is a family of molecular models that undergo tunable 2e-/2H+ redox changes. Complexes [(X2bpy)RuII(en*)2](PF6)2 and [(X2bpy)RuIV(en*-H)2](PF6)2 have been synthesized with bpy=2,2'-bipyridine with 4,4'-subtitutions X=-NMe2, -OMe, -Me, -H, -CF3; and en*=2,3-dimethyl-2,3-butanediamine. They have been characterized by IR, UV-vis, and NMR spectroscopies, XRD, electrochemistry, mass spectrometry, DFT and (TD)DFT computations. The introduction of electron-withdrawing and donating groups at the 4,4'-position of the bpy ligand affects the complexes' redox potentials, pKa's, and Bond Dissociation Free Energies (BDFEs) of the N-H bonds in the en* ligands. The average BDFEs for the overall 2e-/2H+ PCET span over 5 kcal/mol. Notably, these complexes all show marked potential inversion over an extended range, ΔpKa>25 units and ΔE0>1.4 V. Potential inversion remains despite the electronic influence of bpy's substitutions which regulate N-H properties several bonds apart by trans-effect over dπ-molecular orbitals at the Ru center. The experimental and computational results presented in this work support the presence of strong coupling between electrons and protons, for modelling insights of 2e-/2H+ transfer reactivity.

Design, synthesis, and biological evaluation of novel 1-amido-2-one-4-thio-deoxypyranose as potential antitumor agents for multiple myeloma.

This study reported the design and synthesis of novel 1-amido-2-one-4-thio-deoxypyranose as inhibitors of potential drug target TRIP13 for developing new mechanism-based therapeutic agents in the treatment of multiple myeloma (MM). In comparison with the positive control DCZ0415, the most active compounds C16, C18, C20 and C32 exhibited strong anti-proliferative activity against human MM cell lines (ARP-1 and NCI-H929) with IC50 values of 1 âˆ¼ 2 µM. While the surface plasmon resonance (SPR) and ATPase activity assays demonstrated that the representative compound C20 is a potent inhibitor of TRIP13, C20 also showed good antitumor activity in vivo on BALB/c nude mice xenografted with MM tumor cells. An initial structure-activity study showed that the carbonyl group is crucial for anticancer activity. Overall, this study provided novel 1-amido-2-one-4-thio-deoxypyranoses, which are entirely different from previously reported potent inhibitor structures of TRIP13, and thus would aid the development of carbohydrate-based novel agents in MM pharmacotherapy.

Nickel-Catalyzed Electrochemical Cross-Electrophile C(sp2)-C(sp3) Coupling via a NiII Aryl Amido Intermediate.

Cross-electrophile coupling (XEC) between aryl halides and alkyl halides is a streamlined approach for C(sp2)-C(sp3) bond construction, which is highly valuable in medicinal chemistry. Based on a key NiII aryl amido intermediate, we developed a highly selective and scalable Ni-catalyzed electrochemical XEC reaction between (hetero)aryl halides and primary and secondary alkyl halides. Experimental and computational mechanistic studies indicate that an amine secondary ligand slows down the oxidative addition process of the Ni-polypyridine catalyst to the aryl bromide and a NiII aryl amido intermediate is formed in situ during the reaction process. The relatively slow oxidative addition is beneficial for enhancing the selectivity of the XEC reaction. The NiII aryl amido intermediate stabilizes the NiII-aryl species to prevent the aryl-aryl homo-coupling side reactions and acts as a catalyst to activate the alkyl bromide substrates. This electrosynthesis system provides a facile, practical, and scalable platform for the formation of (hetero)aryl-alkyl bonds using standard Ni catalysts under mild conditions. The mechanistic insights from this work could serve as a great foundation for future studies on Ni-catalyzed cross-couplings.

Protonated amine and pyrene co-functionalized sodium alginate templated on reduced graphene oxide for highly efficient removal of formaldehyde and acid pollutants.

Indoor formaldehyde pollution can cause inestimable harm to human health and even cancers, thus studies on the removal of formaldehyde attract extensive attentions. In this paper, an environmentally friendly and low-cost biomass material, sodium alginate (SA) was utilized to prepare pyrene functionalized amido-amine-alginic acid (AmAA-Py) by acidification and two-step amidation, which is subsequently self-assembled on reduced graphene oxide (rGO) by π-π stacking interaction, and the final composites were acidified to afford a highly porous composite material for chemical removal of formaldehyde. The formaldehyde chemical removal performance of composite is evaluated at different conditions and find that 1.0 g of acidified alginate derivatives and graphene composites (HCl·AmAA-Py-rGO) can adsorb 69.2 mg of HCHO. Simultaneously, amino groups in amido-amine derivative of acidified sodium alginate (AmAA) can react with acidic pollutants such as H2S and HCl via forming ionic bonding without generating any other by-products, which enables efficient and environment-friendly removal of acidic pollutants. The subtle design of the highly porous composite material utilizing low-cost SA and rGO with large specific surface area opens up a new methodology for fabricating highly porous materials for efficient removal of formaldehyde and other indoor hazardous pollutants.

Selective cross-metathesis of cellobiose derivatives with amido-functionalized olefinic structures: A model study for synthesis of cellulosic diblock copolymers.

This work describes a model study for synthesis of cellulose-based block copolymers, investigating selective coupling of peracetyl ß-d-cellobiose and perethyl ß-d-cellobiose at their reducing-ends by olefin cross-metathesis (CM). Herein we explore suitable pairs of ω-alkenamides that permit selective, quantitative coupling by CM. Condensation reactions of hepta-O-acetyl-ß-d-cellobiosylamine or hepta-O-ethyl-ß-d-cellobiosylamine with acyl chlorides afforded the corresponding N-(ß-d-cellobiosyl)-ω-alkenamide derivatives with an aromatic olefin or linear olefinic structures. Among the introduced olefinic structures, CM of the undec-10-enamide (Type I olefin) and the acrylamide (Type II olefin) gave the hetero-block tetramers, N-(hepta-O-ethyl-ß-d-cellobiosyl)-N'-(hepta-O-acetyl-ß-d-cellobiosyl)-alkene-α,ω-diamides, with >98 % selectivity. Moreover, selectivity was not influenced by the cellobiose substituents when a Type I olefin with a long alkyl tether was used. Although the amide carbonyl group could chelate the ruthenium atom and reduce CM selectivity, the results indicated that such chelation is suppressed by sterically hindered pyranose rings or the long alkyl chain between the amido group and the double bond. Based on this model study, selective end-to-end coupling of tri-O-ethyl cellulose and acetylated cellobiose was accomplished, proving the concept that this model study with cellobiose derivatives is a useful signpost for selective synthesis of polysaccharide-based block copolymers.

Crystal structure of tetra-phenyl phosphate tetra-kis-[dimethyl (2,2,2-tri-chloro-acet-yl)phos-pho-ramidato]lutetium(III), PPh4[LuL4].

A lutetium(III) complex based on the anion of the ligand dimethyl (2,2,2-tri-chloro-acet-yl)phospho-ramidate (HL) and tetra-phenylphosphonium, of composition PPh4[LuL 4] (L = CAPh = carbacyl-amido-phosphate), or (C24H20)[Lu(C4H6Cl3NO4P)4], has been synthesized and structurally characterized. The X-ray diffraction study of the compound revealed that the lutetium ion is surrounded by four bis-chelating CAPh ligands, forming the complex anion [LuL 4]- with a coordination number of 8[O] for LuIII, while PPh4 + serves as a counter-ion. The coordination geometry around the Lu3+ ion was determined to be a nearly perfect triangular dodeca-hedron. The complex crystallizes in the monoclinic crystal system, space group P21/c, with four mol-ecules in the unit cell. Weak hydrogen bonds O⋯HC(Ph), Cl⋯HC(Ph) and N⋯HC(Ph) are formed between the cations and anions. For a comparative study, HL-based structures were retrieved from the Cambridge Structural Database (CSD) and their geometries and conformations are discussed. A Hirshfeld surface analysis was also performed.

A hydrogel-based ratiometric fluorescent sensor relying on rhodamine B labelled AIE-featured hyperbranched poly(amido amine) for heparin detection.

The fluorescent flexible sensor for point-of-care quantification of clinical anticoagulant drug, Heparin (Hep), is still an urgent need of breakthrough. In this research, a hyperbranched poly(amido amine) (HPA) was decorated with tetraphenylethene (TPE) and Rhodamine B (RhB), constructing a ratiometric fluorescent sensor (TR-HPA) for Hep. When the sensor was exposed to Hep, the TPE units within the probe skeleton would aggregate, resulting in an increasing fluorescent emission at 483 nm. The 580 nm of fluorescence came from RhB enhance, simultaneously, due to the fluorescence resonance energy transfer. As a result, there are two good linear correlation between the fluorescence emission ratio (E483/E580) of TR-HPA and the Hep concentration over a range of 0-1.0 µM, with a low limit of detection of 3.0 nM. Furthermore, we incorporate the TR-HPA probe into a polyvinyl alcohol (PVA) hydrogel matrix to create a flexible fluorescent sensing system platform, denoted as TR-HPA/PVA. This approach offers a straightforward visual detection method by causing a fluorescence color change from pink to blue when trace amounts of Hep are present. The hydrogel-based fluorescent sensor streamlines the detection procedures for Hep in biomedical applications. It shows great potential in rapid and point-of-care human blood clotting condition monitoring, making it suitable for next-generation wearable medical devices.

Design and Synthesis of 6-amido-3-carboxypyridazine Derivatives as Potent T3SS Inhibitors of Salmonella enterica Serovar Typhimurium.

BACKGROUND: Salmonella enterica (S. enterica) serovar Typhimurium, an anaerobic enteric pathogene, could cause human and animal diseases ranging from mild gastroenteritis to whole body serious infections. OBJECTIVE: The goal of this paper was to synthesize new 6-amido-3-carboxypyridazine derivatives with different lengths of side chains with the aim of getting potent antibacterial agents. METHODS: Synthesized compounds were analyzed by analytical techniques, such as 1H NMR, 13C NMR spectra, and mass spectrometry. We designed a series of novel 6-amido-3-carboxypyridazines using FA as the lead compound with the scaffold hopping strategy and their inhibitory activity against the effectors of type III secretion system (T3SS) using SDS-PAGE and western blot analysis for two rounds. Also, the preliminary mechanism of action of this series of compounds on T3SS was performed using real-time qPCR. RESULTS: Nine 6-amido-3-carboxypyridazines was synthesized. The inhibitory activities evaluated showed that compound 2i was the most potent T3SS inhibitor, which demonstrated potent inhibitory activities on the secretion of the T3SS SPI-1 effectors in a dose-dependent manner. The transcription of SPI-1 may be affected by compound 2i through the SicA/InvF regulatory pathway. CONCLUSION: The novel synthetic 6-amido-3-carboxypyridazines could act as potent leads for the development of novel antibacterial agents.

A Linear Two-Coordinate Cr(II) Complex: Synthesis, Characterization, and Reactivity.

The synthesis and characterization of a linear two-coordinate Cr(II) amido complex, Cr{N(t Bu)Dipp}2 (Dipp=2,6-diisopropylphenyl), from the reaction of 1 molar equivalent (equiv) of CrCl2 and 2 equiv. of LiN(t Bu)Dipp is reported. Single-crystal X-ray diffractometry (SC-XRD) analysis revealed that it has a short Cr-N bond distance of 1.8878(9) Å, which could be attributed to the relatively less bulky nature of the amido ligand compared with reported systems. Furthermore, the oxidation reaction of the two-coordinate Cr(II) complex was explored. The oxidation reaction of Cr{N(t Bu)Dipp}2 with the one-electron oxidants AgOTf and [FeCp2 ][BArF 4 ] (BArF 4 - =[B{C6 H3 -3,5-(CF3 )2 }4 ]- ) afforded the trigonal planar three- and bent two-coordinate Cr(III) complexes Cr{N(t Bu)Dipp}2 (OTf) and [Cr{N(t Bu)Dipp}2 ][BArF 4 ], respectively. The reaction of Cr{N(t Bu)Dipp}2 with 1 equiv. of the organic azides AdN3 (Ad=1-adamantyl) and PhN3 afforded the three-coordinate Cr(IV) imido complexes Cr{N(t Bu)Dipp}2 (NAd) and Cr{N(t Bu)Dipp}2 (NPh), respectively. The reaction of Cr{N(t Bu)Dipp}2 and two equiv. of Me3 NO afforded the Cr(VI) dioxo complex Cr{N(t Bu)Dipp}2 (O)2 . The reaction of Cr{N(t Bu)Dipp}2 with 1 equiv. of CyN=C=NCy resulted in the insertion of the carbodiimide into the Cr-N bond, with the formation of a three-coordinate Cr(II) complex. Finally, density functional theory (DFT) calculations were used to elucidate the electronic structure of these complexes.

Preparation and characterization of hemicellulose films reinforced with amino polyhedral oligomeric silsesquioxane for biodegradable packaging.

Biomass is one of the powerful alternatives to petroleum-based packaging materials. Herein, carboxymethyl hemicellulose (CMH) based films (CPF) were prepared using a convenient strategy. The chains of CMH provided the necessary supporting matrix, and the aminopropyl polyhedral oligomeric silsesquioxane (POSS-NH2) regulated the thermal and barrier properties of the CPF. The secondary amide groups and hydrogen bond were appeared in chemical structure, and SEM-EDS results indicated the preferable dispersion and compatibility of POSS-NH2 in CPFs. The thermal degradation temperature (Tonset > 260 °C), the coefficient of linear thermal expansion and glass transition temperature (Tg > 130 °C) have been improved by introduction of POSS-NH2. The tensile strength of CPF showed a higher level of 39.43 MPa with the POSS-NH2 loading of 20 wt%, which was 18.8 % higher than that of CMH film. More importantly, water vapor barrier property of films almost improved by two times, and its value is reduced to 18.82 g m-2 h-1. The shelf life of blueberry was effectively extended by the CPF coating for one week compared with commercial PE film. Therefore, CPF films displayed effective thermal performances, water vapor barrier characteristic and biodegradability, which might be exploited in packaging material for food application.

Evaluation of different Starch Binders on physical quality of fish feed pellets

Abstract Binders are the products that are used to bind, glue or hold the various feed ingredients together in order to maintain pellet integrity. For aqua-culturists, feed manufacturing is an expensive exercise due to the high cost of ingredients along with traditional artificial binders. The use of grain starches as aqua feed binders have advantages which include availability of that binder, nutritional contribution, and minimization of feed cost. A research trial was conducted to test physical properties such as palatability, water stability, dustiness, friability, settling velocity and floatation time of locally available starch i.e. wheat gluten, pea starch and guar gum and to assist their incorporation in on-farm aqua feed. Results revealed that among these three starch, the starch from pea source was proved superior over other two (wheat gluten and guar gum) as all physical quality parameters (dustiness, water stability and friability) revealed better performance of pea starch except pelletability in which guar gum performed best. Although not a single diet proved best in case of flotation time (Tf) and settling velocity (Vset) at varying lengths (6mm, 9mm and 12 mm). This finding indicates the significance of suitable binders for optimal water pollution and sustainable aquaculture. The use of these binders i.e. wheat gluten, pea starch and guar gum in fish feed pellets may also reduce dependence on synthetic binders and minimizes cost.

Resumo Aglutinantes são produtos usados para unir, colar ou manter juntos os vários ingredientes da ração, a fim de conservar a integridade do pellet. Para os aquicultores, a fabricação de ração é uma atividade difícil e cara por causa do alto preço dos aglutinantes artificiais tradicionais. O uso de amidos de grãos como aglutinantes de rações aquáticas tem vantagens que incluem acessibilidade, disponibilidade, contribuição nutricional e minimização do custo da ração. Um ensaio de pesquisa foi conduzido para testar propriedades físicas, como palatabilidade, estabilidade em água, pulverulência, friabilidade, velocidade de sedimentação e tempo de flutuação de amido disponível localmente, ou seja, glúten de trigo, amido de ervilha e goma de guar, e para auxiliar sua incorporação em rações aquáticas. Os resultados revelaram que, entre esses três amidos, o amido de ervilha se mostrou superior aos outros dois (glúten de trigo e goma de guar), pois todos os parâmetros de qualidade física (pulverulência, estabilidade da água e friabilidade) obtiveram melhor desempenho, exceto peletabilidade, em que a goma de guar se destacou. Nenhuma dieta se mostrou melhor no caso de tempo de flotação (Tf) e velocidade de sedimentação em comprimentos variados (6 mm, 9 mm e 12 mm). Essa descoberta indica a importância de aglutinantes adequados para a poluição ótima da água e a aquicultura sustentável. O uso desses aglutinantes, ou seja, glúten de trigo, amido de ervilha e goma de guar, em pellets de ração para peixes também pode reduzir a dependência de aglutinantes sintéticos e minimizar o custo.

Evaluation of different Starch Binders on physical quality of fish feed pellets / Avaliação de diferentes aglutinantes de amido na qualidade física de rações para peixes

Binders are the products that are used to bind, glue or hold the various feed ingredients together in order to maintain pellet integrity. For aqua-culturists, feed manufacturing is an expensive exercise due to the high cost of ingredients along with traditional artificial binders. The use of grain starches as aqua feed binders have advantages which include availability of that binder, nutritional contribution, and minimization of feed cost. A research trial was conducted to test physical properties such as palatability, water stability, dustiness, friability, settling velocity and floatation time of locally available starch i.e. wheat gluten, pea starch and guar gum and to assist their incorporation in on-farm aqua feed. Results revealed that among these three starch, the starch from pea source was proved superior over other two (wheat gluten and guar gum) as all physical quality parameters (dustiness, water stability and friability) revealed better performance of pea starch except pelletability in which guar gum performed best. Although not a single diet proved best in case of flotation time (Tf) and settling velocity (Vset) at varying lengths (6mm, 9mm and 12 mm). This finding indicates the significance of suitable binders for optimal water pollution and sustainable aquaculture. The use of these binders i.e. wheat gluten, pea starch and guar gum in fish feed pellets may also reduce dependence on synthetic binders and minimizes cost.

Aglutinantes são produtos usados para unir, colar ou manter juntos os vários ingredientes da ração, a fim de conservar a integridade do pellet. Para os aquicultores, a fabricação de ração é uma atividade difícil e cara por causa do alto preço dos aglutinantes artificiais tradicionais. O uso de amidos de grãos como aglutinantes de rações aquáticas tem vantagens que incluem acessibilidade, disponibilidade, contribuição nutricional e minimização do custo da ração. Um ensaio de pesquisa foi conduzido para testar propriedades físicas, como palatabilidade, estabilidade em água, pulverulência, friabilidade, velocidade de sedimentação e tempo de flutuação de amido disponível localmente, ou seja, glúten de trigo, amido de ervilha e goma de guar, e para auxiliar sua incorporação em rações aquáticas. Os resultados revelaram que, entre esses três amidos, o amido de ervilha se mostrou superior aos outros dois (glúten de trigo e goma de guar), pois todos os parâmetros de qualidade física (pulverulência, estabilidade da água e friabilidade) obtiveram melhor desempenho, exceto peletabilidade, em que a goma de guar se destacou. Nenhuma dieta se mostrou melhor no caso de tempo de flotação (Tf) e velocidade de sedimentação em comprimentos variados (6 mm, 9 mm e 12 mm). Essa descoberta indica a importância de aglutinantes adequados para a poluição ótima da água e a aquicultura sustentável. O uso desses aglutinantes, ou seja, glúten de trigo, amido de ervilha e goma de guar, em pellets de ração para peixes também pode reduzir a dependência de aglutinantes sintéticos e minimizar o custo.

A plant virus protein, NIa-pro, interacts with Indole-3-acetic acid-amido synthetase, whose levels positively correlate with disease severity.

Potato virus Y (PVY) is an economically important plant pathogen that reduces the productivity of several host plants. To develop PVY-resistant cultivars, it is essential to identify the plant-PVY interactome and decipher the biological significance of those molecular interactions. We performed a yeast two-hybrid (Y2H) screen of Nicotiana benthamiana cDNA library using PVY-encoded NIa-pro as the bait. The N. benthamiana Indole-3-acetic acid-amido synthetase (IAAS) was identified as an interactor of NIa-pro protein. The interaction was confirmed via targeted Y2H and bimolecular fluorescence complementation (BiFC) assays. NIa-pro interacts with IAAS protein and consequently increasing the stability of IAAS protein. Also, the subcellular localization of both NIa-pro and IAAS protein in the nucleus and cytosol was demonstrated. By converting free IAA (active form) to conjugated IAA (inactive form), IAAS plays a crucial regulatory role in auxin signaling. Transient silencing of IAAS in N. benthamiana plants reduced the PVY-mediated symptom induction and virus accumulation. Conversely, overexpression of IAAS enhanced symptom induction and virus accumulation in infected plants. In addition, the expression of auxin-responsive genes was found to be downregulated during PVY infection. Our findings demonstrate that PVY NIa-pro protein potentially promotes disease development via modulating auxin homeostasis.

Preparation of Eco-Friendly Chelating Resins and Their Applications for Water Treatment.

In the present study, two chelating resins were prepared and used for simultaneous adsorption of toxic metal ions, i.e., Cr3+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Pb2+ (MX+). In the first step, chelating resins were prepared starting with styrene-divinylbenzene resin, a strong basic anion exchanger Amberlite IRA 402(Cl-) with two chelating agents, i.e., tartrazine (TAR) and amido black 10B (AB 10B). Key parameters such as contact time, pH, initial concentration, and stability were evaluated for the obtained chelating resins (IRA 402/TAR and IRA 402/AB 10B). The obtained chelating resins show excellent stability in 2M HCl, 2M NaOH, and also in ethanol (EtOH) medium. The stability of the chelating resins decreased when the combined mixture (2M HCl:EtOH = 2:1) was added. The above-mentioned aspect was more evident for IRA 402/TAR compared to IRA 402/AB 10B. Taking into account the higher stability of the IRA 402/TAR and IRA 402/AB 10B resins, in a second step, adsorption studies were carried out on complex acid effluents polluted with MX+. The adsorption of MX+ from an acidic aqueous medium on the chelating resins was evaluated using the ICP-MS method. The following affinity series under competitive analysis for IRA 402/TAR was obtained: Fe3+(44 µg/g) > Ni2+(39.8 µg/g) > Cd2+(34 µg/g) > Cr3+(33.2 µg/g) > Pb2+(32.7 µg/g) > Cu2+ (32.5 µg/g) > Mn2+(31 µg/g) > Co2+(29 µg/g) > Zn2+ (27.5 µg/g). While for IRA 402/AB 10B, the following behavior was observed: Fe3+(58 µg/g) > Ni2+(43.5 µg/g) > Cd2+(43 µg/g) > Cu2+(38 µg/g) > Cr3+(35 µg/g) > Pb2+(34.5 µg/g) > Co2+(32.8 µg/g) > Mn2+(33 µg/g) > Zn2+(32 µg/g), consistent with the decreasing affinity of MX+ for chelate resin. The chelating resins were characterized using TG, FTIR, and SEM analysis. The obtained results showed that the chelating resins prepared have promising potential for wastewater treatment in the context of the circular economy approach.

Polyamidoamine dendrimer decorated graphene oxide as a pH-sensitive nanocarrier for the delivery of hydrophobic anticancer drug quercetin: a remedy for breast cancer.

OBJECTIVES: The aim of this study was to investigate the potential of poly(amido amine) (PAMAM) dendrimer decorated graphene oxide (GO) based nanocarrier for targeted delivery of a hydrophobic anticancer drug, quercetin (QSR). METHODS: GO-PAMAM was successfully synthesized by covalent bonding between GO and NH2-terminated PAMAM dendrimer (zero generation). To investigate drug loading performance, QSR was loaded on the surface of GO as well as GO-PAMAM. Further, the release behaviour of QSR-loaded GO-PAMAM was studied. Finally, an in-vitro sulforhodamine B assay was performed in HEK 293T epithelial cells and MDA MB 231 breast cancer cells. KEY FINDINGS: It was observed that GO-PAMAM shows higher QSR loading capacity compared to GO. Also, synthesized nanocarrier exhibits controlled as well as pH-responsive release of QSR and the amount of QSR released at pH 4 was approximately two times higher than the release at pH 7.4. Furthermore, GO-PAMAM was found to be biocompatible for HEK 293T cells, and a high cytotoxic effect was observed for QSR-loaded GO-PAMAM on MDA MB 231 cells. CONCLUSIONS: The present investigation highlights the potential application of synthesized hybrid materials as a nanocarrier with excellent loading and controlled releasing efficiency for the delivery of the hydrophobic anticancer drug.