Organo-photoredox catalyzed gem-difluoroallylation of ketone-derived dihydroquinazolinones via C(sp3)-C bond and C(sp3)-F bond cleavage.

An organo-photoredox catalyzed gem-difluoroallylation of both acyclic and cyclic ketone derivatives with α-trifluoromethyl alkenes has been demonstrated, thus giving access to a diverse set of gem-difluoroalkenes in moderate to high yields. Pro-aromatic dihydroquinazolinones can be either pre-formed or in situ generated for ketone activation. This reaction is characterized by readily available starting materials, mild reaction conditions, and broad substrate scope. The feasibility of this reaction has been highlighted by the late-stage modification of several natural products and drug-like molecules as well as the in vitro antifungal activity.

Side-Chain-Dependent Functional Intercalations in Graphene Oxide Membranes for Selective Water and Ion Transport.

Subnanometer interlayer space in graphene oxide (GO) laminates is desirable for use as permselective membrane nanochannels. Although the facile modification of the local structure of GO enables various nanochannel functionalizations, precisely controlling nanochannel space is still a challenge, and the roles of confined nanochannel chemistry in selective water/ion separation have not been clearly defined. In this study, macrocyclic molecules with consistent basal plane but varying side groups were used to conjunct with GO for modified nanochannels in laminates. We demonstrated the side-group dependence of both the angstrom-precision tunability for channel free space and the energy barrier setting for ion transport, which challenges the permeability-selectivity trade-off with a slightly decreased permeance from 1.1 to 0.9 L m-2 h-1 bar-1 but an increased salt rejection from 85% to 95%. This study provides insights into the functional-group-dependent intercalation modifications of GO laminates for understanding laminate structural control and nanochannel design.

Iron-Catalyzed Allylic C(sp3)-H Silylation: Spin-Crossover-Efficiency-Determined Chemoselectivity.

The nuanced role of spin effects remains a critical gap in designing proficient open-shell catalysts. This study elucidates an iron-catalyzed allylic C(sp3)-H silylation/alkyne hydrosilylation reaction, in which the spin state of the open-shell iron catalyst dictates the reaction kinetics and pathway. Specifically, spin crossover led to alkyne hydrosilylation, whereas spin conservation resulted in a novel allylic C(sp3)-H silylation reaction. This chemoselectivity, governed by the spin-crossover efficiency, reveals an unexpected dimension in spin effects and a first in the realm of transition-metal-catalyzed in situ silylation of allylic C(sp3)-H bonds, which had been previously inhibited by the heightened reactivity of alkenes in hydrosilylation reactions. Furthermore, this spin crossover can either accelerate or hinder the reaction at different stages within a single catalytic reaction, a phenomenon scarcely documented. Moreover, we identify a substrate-assisted C-H activation mechanism, a departure from known ligand-assisted processes, offering a fresh perspective on C-H activation strategies.

Iron-Catalyzed Stereoconvergent 1,4-Hydrosilylation of Conjugated Dienes.

Stereoconvergent transformation of E/Z mixtures of olefins to products with a single steric configuration is of great practical importance but hard to achieve. Herein, we report an iron-catalyzed stereoconvergent 1,4-hydrosilylation reactions of E/Z mixtures of readily available conjugated dienes for the synthesis of Z-allylsilanes with high regioselectivity and exclusive stereoselectivity. Mechanistic studies suggest that the reactions most likely proceed through a two-electron redox mechanism. The stereoselectivity of the reactions is ultimately determined by the crowded reaction cavity of the α-diimine ligand-modified iron catalyst, which forces the conjugated diene to coordinate with the iron center in a cis conformation, which in turn results in generation of an anti-π-allyl iron intermediate. The mechanism of this stereoconvergent transformation differs from previously reported mechanisms of other related reactions involving radicals or metal-hydride species.

Iron-Catalyzed Vinylzincation of Terminal Alkynes.

Organozinc reagents are among the most commonly used organometallic reagents in modern synthetic chemistry, and multifunctionalized organozinc reagents can be synthesized from structurally simple, readily available ones by means of alkyne carbozincation. However, this method suffers from poor tolerance for terminal alkynes, and transformation of the newly introduced organic groups is difficult, which limits its applications. Herein, we report a method for vinylzincation of terminal alkynes catalyzed by newly developed iron catalysts bearing 1,10-phenanthroline-imine ligands. This method provides efficient access to novel organozinc reagents with a diverse array of structures and functional groups from readily available vinylzinc reagents and terminal alkynes. The method features excellent functional group tolerance (tolerated functional groups include amino, amide, cyano, ester, hydroxyl, sulfonyl, acetal, phosphono, pyridyl), a good substrate scope (suitable terminal alkynes include aryl, alkenyl, and alkyl acetylenes bearing various functional groups), and high chemoselectivity, regioselectivity, and stereoselectivity. The method could significantly improve the synthetic efficiency of various important bioactive molecules, including vitamin A. Mechanistic studies indicate that the new iron-1,10-phenanthroline-imine catalysts developed in this study have an extremely crowded reaction pocket, which promotes efficient transfer of the vinyl group to the alkynes, disfavors substitution reactions between the zinc reagent and the terminal C-H bond of the alkynes, and prevents the further reactions of the products. Our findings show that iron catalysts can be superior to other metal catalysts in terms of activity, chemoselectivity, regioselectivity, and stereoselectivity when suitable ligands are used.

Transcriptomic analysis provides insights into the AUXIN RESPONSE FACTOR 6-mediated repression of nicotine biosynthesis in tobacco (Nicotiana tabacum L.).

KEY MESSAGE: NtARF6 overexpression represses nicotine biosynthesis in tobacco. Transcriptome analysis suggests that NtARF6 acts as a regulatory hub that connect different phytohormone signaling pathways to antagonize the jasmonic acid-induced nicotine biosynthesis. Plant specialized metabolic pathways are regulated by a plethora of molecular regulators that form complex networks. In Nicotiana tabacum, nicotine biosynthesis is regulated by transcriptional activators, such as NtMYC2 and the NIC2-locus ERFs. However, the underlying molecular mechanism of the regulatory feedback is largely unknown. Previous research has shown that NbARF1, a nicotine synthesis repressor, reduces nicotine accumulation in N. benthamiana. In this study, we demonstrated that overexpression of NtARF6, an ortholog of NbARF1, was able to reduce pyridine alkaloid accumulation in tobacco. We found that NtARF6 could not directly repress the transcriptional activities of the key nicotine pathway structural gene promoters. Transcriptomic analysis suggested that this NtARF6-induced deactivation of alkaloid biosynthesis might be achieved by the antagonistic effect between jasmonic acid (JA) and other plant hormone signaling pathways, such as ethylene (ETH), salicylic acid (SA), abscisic acid (ABA). The repression of JA biosynthesis is accompanied by the induction of ETH, ABA, and SA signaling and pathogenic infection defensive responses, resulting in counteracting JA-induced metabolic reprogramming and decreasing the expression of nicotine biosynthetic genes in vivo. This study provides transcriptomic evidence for the regulatory mechanism of the NtARF6-mediated repression of alkaloid biosynthesis and indicates that this ARF transcription factor might act as a regulatory hub to connect different hormone signaling pathways in tobacco.

Enantioselective Silicon-Directed Nazarov Cyclization.

The Nazarov electrocyclization reaction is a convenient, widely used method for construction of cyclopentenones. In the past few decades, catalytic asymmetric versions of the reaction have been extensively studied, but the strategies used to control the position of the double bond limit the substituent pattern of the products and thus the synthetic applications of the reaction. Herein, we report highly enantioselective silicon-directed Nazarov reactions which were cooperatively catalyzed by a Lewis acid and a chiral Brønsted acid. The chiral cyclopentenones we synthesized using this method generally cannot be obtained by means of other catalytic enantioselective reactions, including previously reported methods for enantioselective Nazarov cyclization. The silicon group in the dienone substrate stabilized the ß-carbocation of the intermediate, thereby determining the position of the double bond in the product. Mechanistic studies suggested that the combination of Lewis and Brønsted acids synergistically activated the dienone substrate and that the enantioselectivity of the reaction originated from a chiral Brønsted acid promoted proton transfer reaction of the enol intermediate.

Cold stress in the harvest period: effects on tobacco leaf quality and curing characteristics.

BACKGROUND: Weather change in high-altitude areas subjects mature tobacco (Nicotiana tabacum L.) to cold stress, which damages tobacco leaf yield and quality. A brupt diurnal temperature differences (the daily temperature dropping more than 20 °C) along with rainfall in tobacco-growing areas at an altitude above 2450 m, caused cold stress to field-grown tobacco. RESULTS: After the flue-cured tobacco suffered cold stress in the field, the surface color of tobacco leaves changed and obvious large browning areas were appeared, and the curing availability was extremely poor. Further research found the quality of fresh tobacco leaves, the content of key chemical components, and the production quality were greatly reduced by cold stress. We hypothesize that cold stress in high altitude environments destroyed the antioxidant enzyme system of mature flue-cured tobacco. Therefore, the quality of fresh tobacco leaves, the content of key chemical components, and the production quality were greatly reduced by cold stress. CONCLUSION: This study confirmed that cold stress in high-altitude tobacco areas was the main reason for the browning of tobacco leaves during the tobacco curing process. This adverse environment seriously damaged the quality of tobacco leaves, but can be mitigated by pay attention to the weather forecast and pick tobacco leaves in advance.

Iron-Catalyzed Regiodivergent Alkyne Hydrosilylation.

Although tremendous effort has been devoted to the development of methods for iron catalysis, few of the catalysts reported to date exhibit clear superiority to other metal catalysts, and the mechanisms of most iron catalysis remain unclear. Herein, we report that iron complexes bearing 2,9-diaryl-1,10-phenanthroline ligands exhibit not only unprecedented catalytic activity but also unusual ligand-controlled divergent regioselectivity in hydrosilylation reactions of various alkynes. The hydrosilylation protocol described herein provides a highly efficient method for preparing useful di- and trisubstituted olefins on a relatively large scale under mild conditions, and its use markedly improved the synthetic efficiency of a number of bioactive compounds. Mechanistic studies based on control experiments and density functional theory calculations were performed to understand the catalytic pathway and the observed regioselectivity.

Iron-Catalyzed Dihydrosilylation of Alkynes: Efficient Access to Geminal Bis(silanes).

Geminal bis(silanes) are versatile synthetic building blocks owing to their stability and propensity to undergo a variety of transformations. However, the scarcity of catalytic methods for their synthesis limits their structural diversity and thus their utility for further applications. Herein we report a new method for synthesis of geminal bis(silanes) by means of iron-catalyzed dihydrosilylation of alkynes. Iron catalysts were distinctly superior to the other tested catalysts, which clearly demonstrates that novel reactivity can be found by using iron catalysts. This method features 100% atom economy, regiospecificity, mild reaction conditions, and readily available starting materials. Using this method, we prepared a new type of geminal bis(silane) with secondary silane moieties, the Si-H bonds of which can easily undergo various transformations, facilitating the synthetic applications of these compounds. Preliminary mechanistic studies demonstrated that the reaction proceeds via two iron-catalyzed hydrosilylation reactions, the first generating ß-( E)-vinylsilanes and the second producing geminal bis(silanes).

Cerebral Dopamine Neurotrophic Factor (CDNF) Has Neuroprotective Effects against Cerebral Ischemia That May Occur through the Endoplasmic Reticulum Stress Pathway.

Cerebral dopamine neurotrophic factor (CDNF), previously known as the conserved dopamine neurotrophic factor, belongs to the evolutionarily conserved CDNF/mesencephalic astrocyte-derived neurotrophic factor MANF family of neurotrophic factors that demonstrate neurotrophic activities in dopaminergic neurons. The function of CDNF during brain ischemia is still not known. MANF is identified as an endoplasmic reticulum (ER) stress protein; however, the role of CDNF in ER stress remains to be fully elucidated. Here, we test the neuroprotective effect of CDNF on middle cerebral artery occlusion (MCAO) rats and neurons and astrocytes treated with oxygen⁻glucose depletion (OGD). We also investigate the expression of CDNF in cerebral ischemia and in primary neurons treated with ER stress-inducing agents. Our results show that CDNF can significantly reduce infarct volume, reduce apoptotic cells and improve motor function in MCAO rats, while CDNF can increase the cell viability of neurons and astrocytes treated by OGD. The expression of CDNF was upregulated in the peri-infarct tissue at 2 h of ischemia/24 h reperfusion. ER stress inducer can induce CDNF expression in primary cultured neurons. Our data indicate that CDNF has neuroprotective effects on cerebral ischemia and the OGD cell model and the protective mechanism of CDNF may occur through ER stress pathways.

Efficacy in bowel movement and change of gut microbiota on adult functional constipation patients treated with probiotics-containing products: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to pool the efficacy in bowel movement and explore the change of gut microbiota on adult functional constipated patients after probiotics-containing products treatment. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Cochrane Library for published studies and ClinicalTrials.gov for 'grey' researches were independently investigated for randomised controlled trials up to November 2022. ELIGIBILITY CRITERIA, DATA EXTRACTION AND SYNTHESIS: The intervention was probiotics-containing product, either probiotics or synbiotics, while the control was placebo. The risk of bias was conducted. The efficacy in bowel movement was indicated by stool frequency, stool consistency and Patient Assessment of Constipation Symptom (PAC-SYM), while the change of gut microbiota was reviewed through α diversity, ß diversity, change/difference in relative abundance and so on. The subgroup analysis, sensitivity analysis and random-effect meta-regression were conducted to explore the heterogeneity. The Grading of Recommendations Assessment Development and Evaluation was conducted to grade the quality of evidence. RESULTS: 17 studies, comprising 1256 participants, were included with perfect agreements between two researchers (kappa statistic=0.797). Compared with placebo, probiotics-containing products significantly increased the stool frequency (weighted mean difference, WMD 0.93, 95% CI 0.47 to 1.40, p=0.000, I²=84.5%, 'low'), improved the stool consistency (WMD 0.38, 95% CI 0.05 to 0.70, p=0.023, I²=81.6%, 'very low') and reduced the PAC-SYM (WMD -0.28, 95% CI: -0.45 to -0.11, p=0.001, I²=55.7%, 'very low'). In subgroup analysis, synbiotics was superior to probiotics to increase stool frequency. Probiotics-containing products might not affect α or ß diversity, but would increase the relative abundance of specific strain. CONCLUSIONS: Probiotics-containing products, significantly increased stool frequency, improved stool consistency, and alleviated functional constipation symptoms. They increased the relative abundance of specific strain. More high-quality head-to-head randomised controlled trials are needed.

A label free fluorescent aptamer sensor based on the combined action of Graphene oxide and SYBR Green I for the detection of Aflatoxin B1.

Here, based on the characteristics of Graphene oxide(GO) and SYBR Green I(SGI) dye, an enzyme-free and label-free fluorescent biosensor with signal amplification through DNA strand reaction is proposed for the detection of Aflatoxin B1(AFB1) in food safety. Firstly, without the addition of AFB1, the substrate in the system includes a double stranded Apt-S with a long sticky end and two hairpins H1 and H2. Although the complementary pairing of bases may exhibit fluorescence due to the insertion of SGI dyes, the use of GO, which is highly capable of adsorbing single stranded parts and quenching fluorescence, cleverly reduces the background fluorescence. Adding the target AFB1 triggers DNA inter chain reactions, generating a large amount of long double stranded DNA H1-H2, thereby generating strong fluorescence signals under the action of SGI. More importantly, logical theory verification and computer simulation were conducted before biological experiments, providing a theoretical basis for the implementation of the biosensor. After analysis, the fluorescence biosensor exhibits a good linear relationship with AFB1 concentration in the range of 5-50nM, with a detection limit of 0.76nM. It also has good specificity, anti-interference ability, and practical application ability, and has broad application prospects in the field of food safety.

Spin effect on redox acceleration and regioselectivity in Fe-catalyzed alkyne hydrosilylation.

Iron catalysts are ideal transition metal catalysts because of the Earths abundant, cheap, biocompatible features of iron salts. Iron catalysts often have unique open-shell structures that easily undergo spin crossover in chemical transformations, a feature rarely found in noble metal catalysts. Unfortunately, little is known currently about how the open-shell structure and spin crossover affect the reactivity and selectivity of iron catalysts, which makes the development of iron catalysts a low efficient trial-and-error program. In this paper, a combination of experiments and theoretical calculations revealed that the iron-catalyzed hydrosilylation of alkynes is typical spin-crossover catalysis. Deep insight into the electronic structures of a set of well-defined open-shell active formal Fe(0) catalysts revealed that the spin-delocalization between the iron center and the 1,10-phenanthroline ligand effectively regulates the iron center's spin and oxidation state to meet the opposite electrostatic requirements of oxidative addition and reductive elimination, respectively, and the spin crossover is essential for this electron transfer process. The triplet transition state was essential for achieving high regioselectivity through tuning the nonbonding interactions. These findings provide an important reference for understanding the effect of catalyst spin state on reaction. It is inspiring for the development of iron catalysts and other Earth-abundant metal catalysts, especially from the point of view of ligand development.

A enzyme-free fluorescence quenching sensor for amplified detection of kanamycin in milk based on competitive triggering strategies.

In this work, we constructed a FAM fluorescence quenching biosensor based on an aptamer competition recognition and enzyme-free amplification strategy. We design a competing unit consisting of an aptamer chain and a complementary chain, and a catalytic hairpin self-assembly (CHA) unit consisting of two hairpins in which the complementary chain can trigger the catalytic hairpin self-assembly. In the initial state, the aptamer chain is combined with the complementary chain, the catalytic hairpin self-assembly unit is inhibited, the FAM fluorescence group was far away from the BHQ1 quenching group, and the fluorescence is turn-on. In the presence of kanamycin, the aptamer chain recognizes kanamycin and doesn't form double chains, resulting in the free complementary chain triggering hairpin 1 (H1), and then H1 triggering hairpin 2 (H2), FAM fluorophore is close to the BHQ1 quenching group, and the fluorescence is off-on. When H1 and H2 form a cyclic reaction, enzyme-free amplification is achieved and there is significant output of the fluorescence signal. Therefore, the biosensor has good performance in detecting kanamycin, the detection line is 54 nM, the linear range is 54 nM-0.9 µM, and it can achieve highly selective detection of kanamycin. Kanamycin residue may cause serious harm to human health. The high sensitivity detection of kanamycin is urgent, so this project has a great application potential for food detection.

One-Step Phase Separation and Mineralization Fabrication of Membranes for Oily Wastewater Treatment.

Oily wastewater threatens the environment and the human health. Membrane technology offers a simple and efficient alternative to separating oil and water. However, complex membrane modifications are usually employed to optimize the separation performance. In this research, we develop an extremely simple one-step method to in situ calcium carbonate (CaCO3) nanoparticles onto a porous polyketone (PK) membrane via a nonsolvent induced phase separation (NIPS)-mineralization strategy. We utilized the unique chemical property of PK, which allows it to dissolve in a resorcinol aqueous solution. PK was mixed with tannic acid (TA) and calcium chloride (CaCl2) in a resorcinol aqueous solution to fabricate a casting solution. The activated membrane was cast and immersed into a sodium carbonate (Na2CO3) aqueous solution for taking the one-step NIPS-mineralization process. This proposed NIPS-mineralization mechanism comes to two conclusions: (i) the resulting membrane with comprehensive oleophobic properties and enhanced permeation flux for applications of oil/water separation with ultralow fouling and (ii) simplified the procedure to optimize the membrane performance using regular NIPS steps. The current work explores a one-step NIPS-mineralization technique that offers a novel approach to preparing membranes with highly efficient oil/water separation performance.

Fabrication of polydopamine/rGO Membranes for Effective Radionuclide Removal.

In this work, a novel polydopamine/reduced graphene oxide (PDA/rGO) nanofiltration membrane was prepared to efficiently and stably remove radioactive strontium ions under an alkaline environment. Through the incorporation of PDA and thermal reduction treatment, not only has the interlayer spacing of graphene oxide (GO) nanosheets been appropriately regulated but also an improved antiswelling property has been achieved. The dosage of GO, reaction time with PDA, mass ratio of PDA to GO, and thermal treatment temperature have been optimized to achieve a high-performance PDA/rGO membrane. The resultant PDA/rGO composite membrane has exhibited excellent long-term stability at pH 11 and maintains a steady strontium rejection of over 90%. Moreover, the separation mechanism of the PDA/rGO membrane has been systematically investigated and determined to be a synergistic effect of charge repulsion and size exclusion. Results have indicated that PDA/rGO could be considered as a promising candidate for the separation of Sr2+ ions from nuclear industry wastewater.

Iron-Catalyzed Alkene Hydroalumination.

Hydroalumination of olefins generally gives thermodynamically controlled anti-Markovnikov addition selectivity in literatures. In this paper, a highly Markovnikov hydroalumination of aromatic terminal alkenes was realized to prepare various new benzylaluminum complexes by using the well-defined 2,9-diaryl-1,10-phenanthroline modified iron complex as the catalyst and commercially available DIBAL-H as the aluminum hydride reagent. This is the first ironcatalyzed alkene hydroalumination, and the regioselectivity observed in this study is different from the related reactions reported in the literatures.

Development and analysis of a universal label-free micro/nano component for three-channel detection of silver ions, mercury ions, and tetracycline.

In this paper, an enzyme-free and label-free fluorescent nanomodule is proposed for rapid, simple and sensitive detection of Ag+, Hg2+ and tetracycline (TC). The strategy is cleverly designed to enable multiple-purpose detection with as little as 31 nt of ssDNA. Both the embedded dye SYBR Green I and the nanomaterial graphene oxide (GO) are able to distinguish single-stranded DNA from double-stranded DNA; thus, the combination of the two instead of using traditional molecular beacon (MB)-labeled fluorophores and quencher groups can effectively reduce the cost of experiments while efficiently reducing the background noise. Performance testing experiments confirmed the stability and selectivity of the platform; the limits of detection (LODs) of Ag+ and Hg2+ were 1.41 nM and 1.79 nM, respectively, and the detection range were within the WHO standards. In addition, only some base sequences in the flexible functional domain of the nanoloop needed to be programmed to build a universal platform, which was feasible using TC as a target. Therefore, the designed nanomodule has the potential to detect various types of targets, such as antibiotics, proteins, and target genes, and has broad application prospects in environmental monitoring, food testing, and disease diagnosis.

[Effect of sodium alginate-g-deferoxamine/chitosan microspheres on osteogenic differentiation of rat bone mesenchymal stem cells].

PURPOSE: To explore the effect of sodium alginate-g-deferoxamine/chitosan (SA-g-DFO/CS) microspheres on proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs). METHODS: A kind of SA-g-DFO/CS microsphere was developed through electrostatic interaction between porous chitosan microspheres and sodium alginate chemically grafted on the surface of DFO. Its morphology, porosity rate, pore size and sustained release of DFO in vitro were examined. Rat BMSCs were isolated and co-cultured with microspheres in osteogenic differentiation medium. MTT assay was used to study the influence of cell proliferation, and Calcein-AM/PI staining was used to observe the cell viability. Alkaline phosphatase (ALP) activity assay was conducted. PCR was used to detect the expression of genes related to angiogenesis and osteogenesis. Statistical analysis was performed using SPSS 22.0 software package. RESULTS: The SA-g-DFO/CS porous microspheres were successfully prepared with a sustained re6lease of DFO. Compared with SA/CS microspheres, the SA-g-DFO/CS microspheres were conducive to cell proliferation and differentiation, with the increases in expression level of ALP, related angiogenesis genes HIF-1α, VEGF and osteogenesis genes COLI, OCN. CONCLUSIONS: The SA-g-DFO/CS porous microspheres can provide a new choice for the development of alveolar bone regeneration.