Stabilizing High-Valence Copper(I) Sites with Cu-Ni Interfaces Enhances Electroreduction of CO2 to C2+ Products.

In this study, the copper-nickel (Cu-Ni) bimetallic electrocatalysts for electrochemical CO2 reduction reaction(CO2RR) are fabricated by taking the finely designed poly(ionic liquids) (PIL) containing abundant Salen and imidazolium chelating sites as the surficial layer, wherein Cu-Ni, PIL-Cu and PIL-Ni interaction can be readily regulated by different synthetic scheme. As a proof of concept, Cu@Salen-PIL@Ni(NO3)2 and Cu@Salen-PIL(Ni) hybrids differ significantly in the types and distribution of Ni species and Cu species at the surface, thereby delivering distinct Cu-Ni cooperation fashion for the CO2RR. Remarkably, Cu@Salen-PIL@Ni(NO3)2 provides a C2+ faradaic efficiency (FEC2+) of 80.9% with partial current density (jC 2+) of 262.9 mA cm-2 at -0.80 V (versus reversible hydrogen electrode, RHE) in 1 m KOH in a flow cell, while Cu@Salen-PIL(Ni) delivers the optimal FEC2+ of 63.8% at jC2+ of 146.7 mA cm-2 at -0.78 V. Mechanistic studies indicates that the presence of Cu-Ni interfaces in Cu@Salen-PIL@Ni(NO3)2 accounts for the preserve of high-valence Cu(I) species under CO2RR conditions. It results in a high activity of both CO2-to-CO conversion and C-C coupling while inhibition of the competitive HER.

Sn-Ag Synergistic Effect Enhances High-Rate Electrocatalytic CO2 -to-Formate Conversion on Porous Poly(Ionic Liquid) Support.

The electrocatalytic transformation of carbon dioxide (CO2 ) to formate is a promising route for highly efficient conversion and utilization of CO2 gas, due to the low production cost and the ease of storage of formate. In this work, porous poly(ionic liquid) (PPIL)-based tin-silver (Sn-Ag) bimetallic hybrids (PPILm -Snx Ag10- x ) are prepared for high-performance formate electrolytic generation. Under optimal conditions, an excellent formate Faradaic efficiency of 95.5% with a high partial current density of 214.9 mA cm-2 is obtained at -1.03 V (vs reversible hydrogen electrode). Meanwhile, the high selectivity of formate (>≈83%) is maintained in a wide potential range (>630 mV). Mechanistic studies demonstrate that the presence of Ag-species is vital for the formation, maintenance, and high dispersion of tetravalent Sn(IV)-species, which accounts for the active sites for CO2 -to-formate conversion. Further, the introduction of Ag-species significantly enhances the activity by increasing the electron density near the Fermi energy level.

Ame-miR-980-3p participates in autophagy-mediated midgut remodelling in Apis mellifera via targeting Atg2B.

Autophagy is a process that serves to degrade damaged proteins and organelles, thereby promoting cell homeostasis, differentiation, development and survival. Many miRNAs have been found to have regulatory roles in autophagy. In insects, it has been shown that autophagy is involved in hormone-regulated programmed cell death during metamorphic midgut remodelling. However, whether this is also true during the remodelling of the honey bee midgut is unclear. In the present study, we explored the relationship between autophagy and midgut remodelling and sought to identify miRNAs involved in this physiological process. We found that autophagy occurred during midgut remodelling and that the inhibition of autophagy resulted in midgut dysplasia in prepupae. Differentially expressed miRNAs enriched in the autophagy signalling pathway during midgut remodelling were identified by small RNA-seq. Ame-miR-980-3p, which targets the autophagy-related gene Atg2B, was screened out. Furthermore, abnormal expression of ame-miR-980-3p in the pupal stage led to the thinning of the midgut wall of newly emerged bees (NE). When ame-miR-980-3p expression was inhibited, the intestinal villi of NE bees became significantly shorter and sparse, and the lipid signal in the peritrophic matrix of Pb almost disappeared, indicating that the adult midgut was underdeveloped and the lipid absorption ability was weakened. Taken together, ame-miR-980-3p targeted Atg2B to participate in the regulation of midgut autophagy in the pupae, and the abnormal expression of ame-miR-980-3p would interfere with cell proliferation and death in the process of midgut remodelling, hinder the formation of adult midgut and eventually lead to adult midgut dysplasia and affect the lipid absorption function of the midgut in Apis mellifera.

Scalable Palladium-Catalyzed Alkoxycarbonylation of Conjugated Dienes.

The Pd(cod)Cl2-catalyzed alkoxycarbonylation of conjugated dienes to ß,γ-unsaturated esters was approached by both intramolecular phosphinesulfonate L1 and intermolecular PPh3/PTSA in this study. However, the poor solubility of the Pd/L1 complex and the labile monodentate Pd/PPh3 structure restricts the system efficiency, especially for the scale-up application. By contrast, the stable and well-soluble bidentate Xantphos system allows for the quantitative formation of 3-pentenoate (96%) on a gram scale within 6 h in weakly alkaline N-methylpyrrolidone (NMP), which also functions as a basic site to promote the rate-limiting alcoholysis step while reducing the dosage of ligand to a theoretical value.

Ruthenium-catalyzed reductive amination of ketones with nitroarenes and nitriles.

The Ru(dppbsa)-catalyzed reductive amination of ketones with nitroarenes and nitriles using H2 as the environmentally benign hydrogen surrogate is developed in this study. Cross-experiments demonstrated that both reactions are initiated by the reduction of nitroarenes or nitriles to the corresponding amines, followed by condensation with ketones to give imines and thereafter hydrogenation. However, the route to the formation of an amino-ligated Ru complex during the reduction of nitroarenes or nitriles, followed by in situ nucleophilic C-N coupling, cannot be completely excluded. This newly developed versatile method features good functional group tolerance, which provides a novel design platform for homogeneous catalysts in constructing motifs of secondary amines.

Honey bee larval culture in vitro: gut emptying determines the transition from larva to prepupa and recombinant AccApidaecin improves antibacterial activity.

In vitro rearing of honey bee larvae is ideal for bioassay studies; no honey bee stable cell lines are available. Inconsistency of internal development staging of reared larvae and a susceptibility to contamination are common problems encountered. Standardized protocols on rearing larvae in vitro to make the larvae growth and development more similar to that of natural colonies are necessary to ensure the accuracy of experimental results and promote honey bee research as a model organism. Here, we concluded that when larval fasting weight was >160 mg, the time point of gut emptying can be defined as the critical point separating the larval and prepupal stages. In this way, we can conduct precise studies on the prepupal stage, such as organ remodeling during metamorphosis. Simultaneously, we further verified that recombinant AccApidaecin in genetic engineered bacteria added to the larval diet upregulated antibacterial peptide gene expression, and did not stimulate the stress response in larvae, nor did it affect the pupation rate or eclosion rate. This demonstrated that feeding recombinant AccApidaecin can enhance the individual antibacterial ability at the molecular level.

Fox transcription factor AccGRF1 in response to glyphosate stress in Apis cerana cerana.

Glyphosate is an herbicide commonly used in agriculture, and its widespread use has adversely affected the survival of nontarget organisms. Among these organisms, bees in particular are important pollinators, and declining bee populations have severely affected crop yields around the world. However, the molecular mechanism by which glyphosate harms bees remains unclear. In our experiment, we screened and cloned a glyphosate-induced gene in Apis cerana cerana (A. c. cerana) and named glyphosate response factor 1 (AccGRF1). Sequence analysis showed that AccGRF1 contains a winged-helix DNA binding domain, which suggests that it belongs to the Forkhead box (Fox) protein family. qRT-PCR and heterologous expression in Escherichia coli and yeast showed that AccGRF1 can respond to glyphosate and oxidative stress. After AccGRF1 knockdown by means of RNA interference (RNAi), the resistance of A. c. cerana to glyphosate stress improved. The results suggested that AccGRF1 is involved in A. c. cerana glyphosate stress tolerance. This study reveals the functions of Fox transcription factors in response to glyphosate stress and provides molecular insights into the regulation of glyphosate responses in honeybees.

AmAtg2B-Mediated Lipophagy Regulates Lipolysis of Pupae in Apis mellifera.

Lipophagy plays an important role in regulating lipid metabolism in mammals. The exact function of autophagy-related protein 2 (Atg2) has been investigated in mammals, but research on the existence and functions of Atg2 in Apis mellifera (AmAtg2) is still limited. Here, autophagy occurred in honeybee pupae, which targeted lipid droplets (LDs) in fat body, namely lipophagy, which was verified by co-localization of LDs with microtubule-associated protein 1A/1B light chain 3 beta (LC3). Moreover, AmAtg2 homolog B (AmAtg2B) was expressed specifically in pupal fat body, which indicated that AmAtg2B might have special function in fat body. Further, AmAtg2B antibody neutralization and AmAtg2B knock-down were undertaken to verify the functions in pupae. Results showed that low expression of AmAtg2B at the protein and transcriptional levels led to lipophagy inhibition, which down-regulated the expression levels of proteins and genes related to lipolysis. Altogether, results in this study systematically revealed that AmAtg2B interfered with lipophagy and then caused abnormal lipolysis in the pupal stage.

Copper-Catalyzed [4 + 1] Annulation of Enaminothiones with Indoline-Based Diazo Compounds.

A concise synthetic route to spiroindoline-fused S-heterocycles was developed through copper-catalyzed [4 + 1] annulation using enaminothiones as donor-acceptor synthons. Both 3-diazoindolin-2-imines and 3-diazooxindoles were amenable to work as effective C1 building blocks. The reaction proceeds via a copper-catalyzed cascade process involving the in situ generation of copper(I) carbene and C-S/C-C bond formation. This synthetic protocol features the use of readily available substrates, diverse substituent tolerance, and good to excellent yields.

Tunable Construction of Multisubstituted 1,3-Dienes and Allenes via a 1,4-Palladium Migration/Carbene Insertion Cascade.

Efficient palladium-catalyzed vinylic C-H alkenylation and allenylation of gem-disubstituted ethylenes with N-tosylhydrazones of aryl alkyl and diaryl ketones were achieved to access trisubstituted 1,3-dienes and tetrasubstituted allenes, respectively. An aryl to vinyl 1,4-palladium migration/carbene insertion/ß-hydride elimination sequence proceeded to switch the chemo- and regioselectivities to give structurally diverse products. Use of 2-FC6H4OH additive enables enhancement of the reaction efficiency through accelerating the key 1,4-palladium migration process.

Pi-inducedin-situaggregation of sevelamer nanoparticles for vascular embolization.

Decades have witnessed rapid progress of polymeric materials for vascular embolic or chemoembolic applications. Commercially available polymeric embolics range from gelatin foam to synthetic polymers such as poly(vinyl alcohol). Current systems under investigation include tunable, bioresorbable microspheres composed of chitosan or poly(ethylene glycol) derivatives,in situgelling liquid embolics with improved safety profiles, and radiopaque embolics that are trackablein vivo. In this paper, we proposed a concept of 'responsive embolization'. Sevelamer, clinically proved as an inorganic phosphate binder, was ground into nanoparticles. Sevelamer nanoparticle is highly mobile and capable of swelling and aggregating in the presence of endogenous inorganic phosphate, thereby effectively occluding blood flow in the vessel as it was administered as an embolic agent for interventional therapy. Moreover, citrated sevelamer nanoparticles delayed the aggregation, preferable to penetrate deeply into the capillary system. On the rabbit VX2 liver cancer model, both sevelamer particles aggregates occlude the tumor feeding artery, but backflow was found for the pristine one, thereby citrate passivation of sevelamer nanoparticles endows it have potential from 'bench to bedside' as a new type of vascular embolic.

Effect of posaconazole on the concentration of intravenous and oral cyclosporine in patients undergoing hematopoietic stem cell transplantation.

PURPOSE: This study aimed to investigate the interactions between posaconazole (POS) and intravenously/orally administered cyclosporine A (CsA) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. METHODS: We included 118 allogeneic HSCT patients who received CsA and POS simultaneously between January 2017 and June 2020 in this study. The ratio of CsA blood concentration (ng/mL) to dosage (mg/day) (C/D) before and after POS initiation was compared. RESULTS: After the initiation of POS, the level of CsA increased 1 to 2 times in 66% (78/118) of patients compared to those without POS. However, the CsA C/D ratio increased by more than threefold in 6% (7/118) of patients after POS initiation, with an increase of more than fourfold in two patients. The median C/D ratio of CsA increased from 0.89 to 1.23 (P < 0.001) and 0.78 to 1.22 (P < 0.001) after POS initiation when CsA was administered intravenously and orally, respectively. In patients who received POS at the time of transition from intravenous to oral CsA, the value increased from 1.01 to 1.38 (P = 0.001). The route of administration had no significant effect on the change in the CsA C/D ratio (P = 0.615). Additionally, we observed the time required for the C/D ratio to reach a plateau after POS initiation was similar on days 13, 8, and 15 under various scenarios. CONCLUSION: POS treatment increased blood CsA levels. A large variability was found in the fold-change in the CsA C/D ratio. Therefore, CsA doses should be adjusted by closely monitoring the blood levels of CsA after POS initiation.

Highly Efficient Electrocatalytic CO2 Reduction to C2+ Products on a Poly(ionic liquid)-Based Cu0 -CuI Tandem Catalyst.

Electroreduction of CO2 on a polymer-modified Cu-based catalyst has shown high multi-electron reduction (>2 e- ) selectivity, however, most of the corresponding current densities are still too small to support industrial applications. In this work, we designed a poly(ionic liquid) (PIL)-based Cu0 -CuI tandem catalyst for the production of C2+ products with both high reaction rate and high selectivity. Remarkably, a high C2+ faradaic efficiency (FE C 2 + ) of 76.1 % with a high partial current density of 304.2 mA cm-2 is obtained. Mechanistic studies reveal the numbers and highly dispersed Cu0 -PIL-CuI interfaces are vital for such reactivity. Specifically, Cu nanoparticles derived Cu0 -PIL interfaces account for high current density and a moderate C2+ selectivity, whereas CuI species derived PIL-CuI interfaces exhibit high activity for C-C coupling with the local enriched *CO intermediate. Furthermore, the presence of the PIL layer promotes the C2+ selectivity by lowering the barrier of C-C coupling.

Visible-Light-Driven, Palladium-Catalyzed Heck Reaction of Internal Vinyl Bromides with Styrenes.

Functionalized 1,3-dienes were efficiently accessed from visible-light-driven, palladium-catalyzed Heck reaction of S,S-functionalized internal vinyl bromides with styrenes under mild conditions. This Heck reaction showcased tolerance of a wide array of functional groups, afforded the target products in moderate to excellent yields through a radical reaction pathway. The resultant diene products could be further transformed to highly functionalized trisubstituted furan derivatives.

Identification of an Apis cerana zinc finger protein 41 gene and its involvement in the oxidative stress response.

Zinc finger proteins (ZFPs) are a class of transcription factors that contain zinc finger domains and play important roles in growth, aging, and responses to abiotic and biotic stresses. These proteins activate or inhibit gene transcription by binding to single-stranded DNA or RNA and through RNA/DNA bidirectional binding and protein-protein interactions. However, few studies have focused on the oxidation resistance functions of ZFPs in insects, particularly Apis cerana. In the current study, we identified a ZFP41 gene from A. cerana, AcZFP41, and verified its function in oxidative stress responses. Real-time quantitative polymerase chain reaction showed that the transcription level of AcZFP41 was upregulated to different degrees during exposure to oxidative stress, including that induced by extreme temperature, UV radiation, or pesticides. In addition, the silencing of AcZFP41 led to changes in the expression patterns of some known antioxidant genes. Moreover, the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and glutathione S-transferase (GST) in AcZFP41-silenced honeybees were higher than those in a control group. In summary, the data indicate that AcZFP41 is involved in the oxidative stress response. The results provide a theoretical basis for further studies of zinc finger proteins and improve our understanding of the antioxidant mechanisms of honeybees.

N-Hydroxyphthalimide/benzoquinone-catalyzed chlorination of hydrocarbon C-H bond using N-chlorosuccinimide.

The direct chlorination of C-H bonds has received considerable attention in recent years. In this work, a metal-free protocol for hydrocarbon C-H bond chlorination with commercially available N-chlorosuccinimide (NCS) catalyzed by N-hydroxyphthalimide (NHPI) with 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ) functioning as an external radical initiator is presented. Aliphatic and benzylic substituents and also heteroaromatic ones were found to be well tolerated. Both the experiments and theoretical analysis indicate that the reaction goes through a process wherein NHPI functions as a catalyst rather than as an initiator. On the other hand, the hydrogen abstraction of the C-H bond conducted by a PINO species rather than the highly reactive N-centered radicals rationalizes the high chemoselectivity of the monochlorination obtained by this protocol as the latter is reactive towards the C(sp3)-H bonds of the monochlorides. The present results could hold promise for further development of a nitroxy-radical system for the highly selective functionalization of the aliphatic and benzylic hydrocarbon C-H.

A metal-free direct C (sp3)-H cyanation reaction with cyanobenziodoxolones.

A metal-free protocol of direct C(sp3)-H cyanation with cyanobenziodoxolones functioning as both cyanating reagents and oxidants was developed. Unactivated substrates, such as alkanes, ethers and tertiary amines, were thereby transformed to the corresponding nitriles in moderate to high yields. Mechanistic studies indicated that the cyanation proceeded with two potential pathways, which is highly dependent on the substrates: (1) a free radical case for alkanes and ethers and (2) an oxidative case for tertiary amines.

Oxidation of Aromatic Aldehydes to Esters: A Sulfate Radical Redox System.

A mild oxidative esterification of various aromatic aldehydes by sulfate radical redox system was presented. In the reaction pathway exploration, the transiency of MeOSO3- was disclosed, which was generated from esterification between the in situ generated HSO4- and MeOH, a rate-limiting step in the process. More importantly, the selectivity-controlling step was represented by the subsequent nucleophilic displacement between MeOSO3- and aldehydes. The ionic oxidant 1a ((NH4)2S2O8) with more N-H numbers in the cation, as compared with 1c ((n-Bu4N)2S2O8) and 1d ((PyH)2S2O8), has better performance in the oxidative esterification of aldehydes.

Intrathecal miR-96 inhibits Nav1.3 expression and alleviates neuropathic pain in rat following chronic construction injury.

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression post-transcriptionally by binding to their cognate target mRNAs. Emerging evidence suggests that miRNAs are critical regulators of neuronal functions. The expression pattern of miRNAs in the peripheral nervous system after peripheral nerve injury suggest that miRNAs may have important and yet unknown roles in the mechanisms of pain. Thus, we examined the role of miR-96 in neuropathic pain using a rat model of the condition chronic constriction sciatic nerve injury (CCI). We found that miR-96 alleviated neuropathic pain. The level of miR-96 was decreased within the ipsilateral dorsal root ganglion (DRG) after peripheral nerve injury but the Nav1.3 level was increased. Specifically, Intrathecal administration of miR-96 suppressed the expression of Nav1.3 induced by CCI. Further examination revealed that miR-96 inhibited the Nav1.3 mRNA expression in the embryonic DRG neurons in vitro. Our findings suggest that miR-96 participate in the regulation of neuropathic pain through inhibiting the expression of Nav1.3 in the DRG of CCI rats.

Morphologic Analysis of Zirconia Ceramics: Effect of Different Surface Treatments.

PURPOSE: To investigate the effects of airborne-particle abrasion and nanosilica (nano-Si) infiltration treatment on the surface characteristics of dental zirconia. MATERIALS AND METHODS: A total of 15 unsintered zirconia ceramic green bodies (10 × 10 × 3 mm) were divided into three groups (n = 5): Group C, no treatment after sintering; Group S, airborne-particle abrasion with 50-µm aluminum oxide particles after sintering; and Group N, infiltration of nano-Si followed by sintering and hydrofluoric acid (HF) etching. The zirconia disks' surface roughness was analyzed by atomic force microscopy (AFM). The surface morphology of the specimens was analyzed using scanning electron microscopy (SEM), and the chemical composition was analyzed by energy-dispersive x-ray (EDX). Data were statistically analyzed by the Kruskal-Wallis test (P < .05). RESULTS: Zirconia surface treatments by infiltration of nano-Si, sintering, and HF etching showed multiple changes in the surface features. The surface roughness of Groups C, S, and N were 0.88 ± 0.07 µm, 1.26 ± 0.10 µm, and 1.69 ± 0.15 µm, respectively. The surface roughness of Group N was significantly higher than that of Groups C and S (P < .05). EDX analysis showed peaks that corresponded to silica (Si) after infiltration with colloidal Si that disappeared following acid etching. CONCLUSIONS: Infiltrating nano-Si increases the surface roughness of zirconia. The formation of retentive nanopores on the surface potentially improves the zirconia-resin cement bonding strengths.