From antioxidant defense to genotoxicity: Deciphering the tissue-specific impact of AgNPs on marine clam Ruditapes philippinarum.

The escalating use of silver nanoparticles (AgNPs) across various sectors for their broad-spectrum antimicrobial capabilities, has raised concern over their potential ecotoxicological effects on aquatic life. This study explores the impact of AgNPs (50 µg/L) on the marine clam Ruditapes philippinarum, with a particular focus on its gills and digestive glands. We adopted an integrated approach that combined in vivo exposure, biochemical assays, and transcriptomic analysis to evaluate the toxicity of AgNPs. The results revealed substantial accumulation of AgNPs in the gills and digestive glands of R. philippinarum, resulting in oxidative stress and DNA damage, with the gills showing more severe oxidative damage. Transcriptomic analysis further highlights an adaptive up-regulation of peroxisome-related genes in the gills responding to AgNP-induxed oxidative stress. Additionally, there was a noteworthy enrichment of differentially expressed genes (DEGs) in key biological processes, including ion binding, NF-kappa B signaling and cytochrome P450-mediated metabolism of xenobiotics. These insights elucidate the toxicological mechanisms of AgNPs to R. philippinarum, emphasizing the gill as a potential sensitive organ for monitoring emerging nanopollutants. Overall, this study significantly advances our understanding of the mechanisms driving nanoparticle-induced stress responses in bivalves and lays the groundwork for future investigations into preventing and treating such pollutants in aquaculture.

Isolation and identification of Chryseobacterium indologenes and its pathological changes in Pelodiscus sinensis.

The Chinese revered a species of aquatic reptile known as Pelodiscus sinensis as both an edible and medicinal species. When artificially breeding, many deaths occurred at the farmed P. sinensis, mainly due to excessive breeding density, water contamination, and turtles biting each other secondary to bacterial infections. In this study, an isolate of gram-negative bacteria WH0623 was isolated from the liver and kidney of diseased P. sinensis to trace the potential pathogen of this disease. Based on biochemical characteristics and 16S rRNA gene sequencing analyses, this isolated strain of WH0623 was identified as Chryseobacterium indologenes. The strain's median lethal dose (LD50 ) was 3.3 × 105 colony-forming units (CFU)/g per fish weight tested using artificial infection. Histopathological analysis revealed pathological changes, including cell swelling, hyperaemia, and necrosis in many tissues. Antibiotic susceptibility tests revealed that the bacteria WH0623 was susceptible to doxycycline, sulphonamides, ceftazidime, norfloxacin, and ciprofloxacin. These antibiotics could treat the disease. In conclusion, the pathogen causing the death of farmed P. sinensis was isolated and identified, and a drug-sensitive test was conducted. Our findings contribute to the future diagnosis and treatment of the disease.

Triazole-modified Ru-carbene complexes: A valid olefin metathesis pre-catalyst for dynamic covalent chemistry via C=C bond formation.

The 1,2,3-triazole coordinated ruthenium carbene complexes (TA-Ru) were reported for the first time as a new class of modified Grubbs catalyst to achieve challenging olefin metathesis at higher temperatures without catalyst decomposition. Previously reported N-tethered Ru-carbene complexes all suffered from rapid cis/trans isomerization, causing significantly reduced catalyst reactivity. These new TA-Ru complexes hold the active trans-dichloro conformation even at 80 °C, allowing effective olefin metathesis for challenging substrates. With this new TA-Ru catalyst, cross-metathesis (CM), ring-closing metathesis (RCM) and dynamic covalent chemistry (DCvC) were achieved. Excitingly, the reactivity of TA-Ru prevails all previously reported N-coordinated Ru-carbene precatalysts, Grubbs II, and Hoveyda-Grubbs, making the TA-Ru a transformative catalytic system in olefin catalysis.

Seawater quality criteria and ecotoxicity risk assessment of zinc oxide nanoparticles based on data of resident marine organisms in China.

Water quality criteria (WQC) for zinc oxide nanoparticles (ZnO NPs) are crucial due to their extensive industrial use and potential threats to marine organisms. This study conducted toxicity tests using marine organisms in China, revealing LC50 or EC50 values for ZnO NPs ranging from 0.36 to 95.6 mg/L across seven species, among which the salinity lake crustacean zooplankton Artemia salina exhibited the highest resistance, while diatom Phaeodactylum tricornutum the most sensitive. Additionally, the EC10 or maximum acceptable toxicant concentration (MATC) values for ZnO NPs were determined for five species, ranging from 0.03 to 2.82 mg/L; medaka Oryzias melastigma demonstrated the highest tolerance, while mysis shrimp Neomysis awatschensis the most sensitive. Based on the species sensitivity distribution (SSD) method, the derived short-term and long-term WQC for ZnO NPs were 138 µg/L and 8.37 µg/L, respectively. These values were further validated using the sensitive species green algae Chlorella vulgaris, confirming effective protection. There is no environmental risk observed in Jiaozhou Bay, Yellow River Estuary and Laizhou Bay in the northern coastal seas of China. This study provides important reference data for the establishment of water quality standards for nanoparticles.

Gold-Catalyzed Amine Cascade Addition to Diyne-Ene: Enantioselective Synthesis of 1,2-Dihydropyridines.

With the well-documented chemical and biological applications, piperidine and pyridine are among the most important N-heterocycles, and a new synthetic strategy, especially one with an alternative bond-forming design, is of general interest. Using the gold-catalyzed intermolecular condensation of amine and diyne-ene, we report herein the first example of enantioselective 1,2-dihydropyridine synthesis through a formal [3+2+1] fashion (up to 95 % yield, up to 99 % e.e.).

Carboxylic-Phosphoric Anhydrides as Direct Electrophiles for Decarbonylative Hirao Cross-Coupling of Carboxylic Acids: DFT Investigation of Mechanistic Pathway.

In this anniversary issue, we present a DFT study of the mechanism of decarbonylative Hirao cross-coupling of carboxylic-phosphoric anhydrides to afford aryl phosphonates. Traditionally, the direct activation of carboxylic acids to participate in decarbonylative couplings is performed in the presence of carboxylic acid anhydride activators. We discovered that direct dehydrogenative decarbonylative phosphorylation of benzoic acid can be performed in high yield via dehydrogenative and decarbonylative coupling in the presence of phosphite as dual activating and nucleophilic reagent, enabling direct decarbonylative phosphorylation. Control studies demonstrated that carboxylic-phosphoric anhydride (acyl phosphate) is an intermediate in this process. DFT studies were conducted to gain insight into this decarbonylative process and compare the selectivity of C-O and P-O bond activations. Considering the utility of ubiquitous carboxylic acids, this alternative activation pathway may find applications in decarbonylative coupling of carboxylic acids for the synthesis of valuable molecules in organic synthesis.

Identification of Alkoxy Radicals as Hydrogen Atom Transfer Agents in Ce-Catalyzed C-H Functionalization.

The intermediacy of alkoxy radicals in cerium-catalyzed C-H functionalization via H-atom abstraction has been unambiguously confirmed. Catalytically relevant Ce(IV)-alkoxide complexes have been synthesized and characterized by X-ray diffraction. Operando electron paramagnetic resonance and transient absorption spectroscopy experiments on isolated pentachloro Ce(IV) alkoxides identified alkoxy radicals as the sole heteroatom-centered radical species generated via ligand-to-metal charge transfer (LMCT) excitation. Alkoxy-radical-mediated hydrogen atom transfer (HAT) has been verified via kinetic analysis, density functional theory (DFT) calculations, and reactions under strictly chloride-free conditions. These experimental findings unambiguously establish the critical role of alkoxy radicals in Ce-LMCT catalysis and definitively preclude the involvement of chlorine radical. This study has also reinforced the necessity of a high relative ratio of alcohol vs Ce for the selective alkoxy-radical-mediated HAT, as seemingly trivial changes in the relative ratio of alcohol vs Ce can lead to drastically different mechanistic pathways. Importantly, the previously proposed chlorine radical-alcohol complex, postulated to explain alkoxy-radical-enabled selectivities in this system, has been examined under scrutiny and ruled out by regioselectivity studies, transient absorption experiments, and high-level calculations. Moreover, the peculiar selectivity of alkoxy radical generation in the LMCT homolysis of Ce(IV) heteroleptic complexes has been analyzed and back-electron transfer (BET) may have regulated the efficiency and selectivity for the formation of ligand-centered radicals.

Chemoselective Transamidation of Thioamides by Transition-Metal-Free N-C(S) Transacylation.

Thioamides represent highly valuable isosteric in the strictest sense "single-atom substitution" analogues of amides that have found broad applications in chemistry and biology. A long-standing challenge is the direct transamidation of thioamides, a process which would convert one thioamide bond (R-C(S)-NR1 R2 ) into another (R-C(S)-NR3 N4 ). Herein, we report the first general method for the direct transamidation of thioamides by highly chemoselective N-C(S) transacylation. The method relies on site-selective N-tert-butoxycarbonyl activation of 2° and 1° thioamides, resulting in ground-state-destabilization of thioamides, thus enabling to rationally manipulate nucleophilic addition to the thioamide bond. This method showcases a remarkably broad scope including late-stage functionalization (>100 examples). We further present extensive DFT studies that provide insight into the chemoselectivity and provide guidelines for the development of transamidation methods of the thioamide bond.

Effects of electrostatic drag on the velocity of hydrogen migration - pre- and post-transition state enthalpy/entropy compensation.

Ab initio molecular dynamics calculations were used to explore the underlying factors that modulate the velocity of hydrogen migration for 1,2 hydrogen shifts in carbocations in which different groups interact noncovalently with the migrating hydrogen. Our results indicate that stronger electrostatic interactions between the migrating hydrogen and nearby π-systems lead to slower hydrogen migration, an effect tied to entropic contributions from the hydrogen + neighboring group substructures.

Phytochemical identification of Lithocarpus polystachyus extracts by ultra-high-performance liquid chromatography-quadrupole time-of-flight-MS and their protein tyrosine phosphatase 1B and α-glucosidase activities.

Lithocarpus polystachyus leaves exhibit antidiabetic activity and is consumed as a herbal tea in China. In this study, phytochemical profiles of L. polystachyus leaves were identified and characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight-MS in both positive and negative ion modes. A total of 17 compounds were tentatively characterized and identified by accurate mass and characteristic fragment ions. The total phenolic contents in the leaf extracts ranged from 9.0 to 13.4 g gallic acid equivalents/100 g of dry weight (DW). In addition, the effect of these extracts on inhibiting the activities of α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) were evaluated. L. polystachyus extracts demonstrated significant inhibition of α-glucosidase (more than 88.1% at a concentration of 1.25 mg/mL) and acarbose (93.6% at a concentration of 5 mg/mL) while the PTP1B inhibition rate was over 84.3%. The antioxidant capacities of the leaf extracts were determined using 2,2-diphenyl-1-picrylhydrazyl, ABTS, and ferric reducing ability of plasma methods and ranged from 50.5 to 72.5 g trolox, from 43.2 to 77.7 g trolox, and from 5.0 to 10.6 g butylated hydroxytoluene (BHT; equaling trolox or BHT per 100 g of DW), respectively. Based on these results, L. polystachyus can be considered as a functional food owing to its antidiabetic and antioxidative activities, which are attributed to its rich phenolic and dihydrochalcone contents.

A Computational Mechanistic Study of Pd(II)-Catalyzed Enantioselective C(sp3)-H Borylation: Roles of APAO Ligands.

A computational mechanistic study has been performed on Pd(II)-catalyzed enantioselective reactions involving acetyl-protected aminomethyl oxazolines (APAO) ligands that significantly improved reactivity and selectivity in C(sp3)-H borylation. The results support a mechanism including initiation of C(sp3)-H bond activation generating a five-membered palladacycle and ligand exchange, followed by HPO42--promoted transmetalation. These resulting Pd(II) complexes further undergo sequential reductive elimination by coordination of APAO ligands and protonation to afford the enantiomeric products and deliver Pd(0) complexes, which will then proceed by oxidation and deprotonation to regenerate the catalyst. The C(sp3)-H activation is found to be the rate- and enantioselectivity-determining step, in which the APAO ligand acts as the proton acceptor to form the two enantioselectivity models. The results demonstrate that the diverse APAO ligands control the enantioselectivity by differentiating the distortion and interaction between the major and minor pathways.

Enhanced Oral Bioavailability of Celecoxib Nanocrystalline Solid Dispersion based on Wet Media Milling Technique: Formulation, Optimization and In Vitro/In Vivo Evaluation.

Celecoxib (CLX), a selective COX-2 inhibitor, is a biopharmaceutics classification system (BCS) class II drug with its bioavailability being limited by thepoor aqueoussolubility. The purpose of this study was to develop and optimize CLX nanocrystalline(CLX-NC) solid dispersion prepared by the wet medium millingtechnique combined with lyophilizationto enhance oral bioavailability. In formulation screening, the resulting CLX-NC usingpolyvinylpyrrolidone (PVP) VA64 and sodiumdodecyl sulfate (SDS) as combined stabilizers showed the minimum particle size and a satisfactory stability. The formulation and preparation processwere further optimized by central composite experimentaldesign with PVP VA64 concentration (X1), SDS concentration (X2) and milling times (X3) as independent factors and particle size (Y1), polydispersity index (PDI, Y2) and zeta potential (Y3) as response variables. The optimal condition was determined as a combination of 0.75% PVP VA64, 0.11% SDS with milling for 90 min.The particle size, PDI and zeta potential of optimized CLX-NC were found to be 152.4 ± 1.4 nm, 0.191 ± 0.012 and -34.4 ± 0.6 mV, respectively. The optimized formulation showed homogeneous rod-like morphology as observed by scanning electron microscopy and was in a crystalline state as determined by differential scanning calorimetry and powder X-ray diffraction. In a storage stability study, optimized CLX-NC exhibited an excellent physical stability during six months' storage at both the refrigeration and room conditions. In vivo pharmacokinetic research in Sprague-Dawley ratsdisplayed that Cmax and AUC0-∞ of CLX-NC were increased by 2.9 and 3.1 fold, compared with physical mixture. In this study, the screening and optimizing strategy of CLX-NC formulation represents a commercially viable approach forenhancing the oral bioavailability of CLX.

Mechanistic Exploration of Cp*CoIII/RhIII-Catalyzed Carboamination/Olefination of N-Phenoxyacetamides with Alkenes.

A computational study of Cp*CoIII/RhIII-catalyzed carboamination/olefination of N-phenoxyacetamides with alkenes was carried out to elucidate the catalyst-controlled chemoselectivity. The reaction of the two catalysts shares a similar process that involves N-H and C-H activation as well as alkene insertion. Then the reaction bifurcates at the generated seven-membered metallacycle. For Cp*CoIII catalyst, the resulting metallacycle undergoes oxidation addition, reductive elimination, and protonation to yield the carboamination product exclusively. However, the Cp*RhIII catalyst could promote the subsequent olefination pathway via sequential ß-H elimination, reductive elimination, oxidation addition, and protonation, which enables the experimentally observed mixtures of both carboamination and olefination products. Our results uncover that the higher propensity for the ß-H-elimination of the Cp*RhIII than the Cp*CoIII catalyst in the olefination pathway could be responsible for the different selectivity and reactivity of the two catalysts.

Mechanistic Exploration of the Competition Relationship between a Ketone and C═C, C═N, or C═S Bond in the Rh(III)-Catalyzed Carbocyclization Reactions.

The introduction of a C═O, C═C, C═S, or C═N bond has emerged as an effective strategy for carbocycle synthesis. A computational mechanistic study of Rh(III)-catalyzed coupling of alkynes with enaminones, sulfoxonium ylides, or α-carbonyl-nitrones was carried out. Our results uncover the roles of dual directing groups in the three substrates and confirm that the ketone acts as the role of the directing group while the C═C, C═N, or C═S bond serves as the cyclization site. By comparing the coordination of the ketone versus the C═C, C═N, or C═S bond, as well as the chemoselectivity concerning the six- versus five-membered formation, a competition relationship is revealed within the dual directing groups. Furthermore, after the alkyne insertion, instead of the originally proposed direct reductive elimination mechanism, the ketone enolization is found to be essential prior to the reductive elimination. The following C(sp2)-C(sp2) reductive elimination is more favorable than the C(sp3)-C(sp2) formation, which can be explained by the aromaticity difference in the corresponding transition states. The substituent effect on controlling the selectivity was also discussed.

Highly sensitive and selective detection of Pd2+ ions using a ferrocene-rhodamine conjugate triple channel receptor in aqueous medium and living cells.

Herein, a novel ferrocene-rhodamine receptor conjugated with an allylimine bridge was facilely synthesized. This triple channel receptor can selectively and sensitively monitor Pd2+ ions through chromogenic, fluorogenic and electrochemical assays in aqueous medium with a low detection limit (8.46 × 10-9 M) and a fast response (<8 min). It can be applied as a fluorescent probe for effective survey of Pd2+ ions in living cells. Moreover, a plausible recognition mode was proposed and rationalized by theoretical calculations.

Complexity analysis of EEG under magnetic stimulation on acupoint of Guangming(GB37).

Changes in electroencephalogram (EEG) signals under repetitive magnetic stimulation at the acupoint of Guangming (GB37) were analyzed using nonlinear dynamics complexity. C0 complexity is a statistical indicators which can quantify time dynamics of EEG signals. The study compared the C0 complexity under magnetic stimulation at GB37 with those at a mock point, as well as the C0 complexity under visual stimulation before and after magnetic stimulation at GB37. The results showed that the C0 complexity values of EEG signals in the electrode F3,Cz,C4 and P3 were different depending on whether magnetic stimulation was at the GB37 or a mock point (P <; 0.05),and the C0 complexity of magnetic stimulation on GB37 was generally higher than that on mock point. Moreover, EEG signals from visual stimulation before magnetic stimulation at GB37 were significantly different from those after magnetic stimulation at GB37 in two electrodes which were C4 and P3(P <; 0.05). The conclusion of the study is that magnetic stimulation at GB37 has a significant impact on EEG signals. First, EEG complexity during magnetic stimulation at GB37 was significantly higher than that at the mock point in frontal area, central area and parietal area (electrodes F3, Cz, C4 and P3). Second, EEG signals in central area and parietal area (electrodes C4 and P3) resulting from visual stimulation differed depending on whether magnetic stimulation at GB37 was given. The study has important significance for the application of magnetic stimulation on acupoints.

The underlying factors controlling the Pd-catalyzed site-selective alkenylation of aliphatic amines.

The Pd(ii)-catalyzed site-selective δ-C(sp3)-H alkenylation in the presence of more accessible γ-C(sp3)-H bonds is investigated by DFT calculations. Migratory insertion is found to be both the rate-limiting and the selectivity-determining step. The origin of the unusual site-selectivity is originally attributed to the different steric repulsion between the alkyne and palladacycle; however, our theoretical results reveal that the inherent electronic effect instead of steric repulsion determines the site-selectivity. The proposal is further validated by model calculations involving the less sterically hindered 1,2-dimethyl acetylene and acetylene. In addition, a novel HCO3--assisted N-H activation mechanism is reported, and the origin of the regioselectivity of an unsymmetrical alkyne is also studied.

Solvent Mediating a Switch in the Mechanism for Rhodium(III)-Catalyzed Carboamination/Cyclopropanation Reactions between N-Enoxyphthalimides and Alkenes.

Recently, a new synthetic methodology of rhodium-catalyzed carboamination/cyclopropanation from the same starting materials at different reaction conditions has been reported. It provides an efficient strategy for the stereospecific formation of both carbon- and nitrogen-based functionalities across an alkene. Herein we carried out a detailed theoretical mechanistic exploration for the reactions to elucidate the switch between carboamination and cyclopropanation as well as the origin of the chemoselectivity. Instead of the experimentally proposed RhIII-RhI-RhIII catalytic mechanism, our results reveal that the RhIII-RhV-RhIII mechanism is much more favorable in the two reactions. The chemoselectivity is attributed to a combination of electronic and steric effects in the reductive elimination step. The interactions between alkene and the rhodacycle during the alkene migration insertion control the stereoselectivity in the carboamination reactions. The present results disclose a dual role of the methanol solvent in controlling the chemoselectivity.

Computational Mechanistic Study of Redox-Neutral Rh(III)-Catalyzed C-H Activation Reactions of Arylnitrones with Alkynes: Role of Noncovalent Interactions in Controlling Selectivity.

The mechanism of redox-neutral Rh(III)-catalyzed coupling reactions of arylnitrones with alkynes was investigated by density functional theory (DFT) calculations. The free energy profiles associated with the catalytic cycle, involving C(sp2)-H activation, insertion of alkyne, transfer of O atom, cyclization and protodemetalation, are presented and analyzed. An overwhelming preference for alkyne insertion into Rh-C over Rh-O is observed among all pathways, and the most favorable route is determined. The pivalate-assisted C-H activation step is turnover-limiting, and the cyclization step determines the diastereoselectivity of the reaction, with the stereoselectivity arising mainly from the difference of noncovalent interactions in key transition states. The detailed mechanism of O atom transfer, RhIII-RhI-RhIII versus RhIII-RhV-RhIII cycle, is discussed.

Nickel titanates hollow shells: nanosphere, nanorod, and their photocatalytic properties.

Two kinds of hollow shell structured nickel titanates (nanosphere, nanorod) were prepared by the microwave-assisted hydrothermal method using carbon material as the template. Their phase structure, morphology, and optical properties were well characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and UV-vis diffuse reflectance spectroscopy (DRS). Comparing with the template-free NiTiO3 (NiTiO3-TF), the two kinds of hollow shell structured NiTiO3 have larger Brunauer-Emmet-Teller (BET) surface areas. Both NiTiO3 nanosphere (NiTiO3-NS) and nanorod (NiTiO3-NR) showed remarkably photocatalytic H2 evolution from the methanol aqueous solution under full-arc lamp and visible light. Additional, their photocatalytic activities were also determined by photo-degradation of methyl blue (MB), and the degradation yield reached nearly 100% within 100 min on NiTiO3-NR under visible light. Whatever in photocatalytic H2 evolution or MB degradation, their photocatalytic activities all followed the order: NiTiO3-NR > NiTiO3-NS > NiTiO3-TF. The higher photocatalytic activities of the hollow shelled NiTiO3 should be due to their larger BET surface areas and more utilization of the incident light.