Dual N-Heterocyclic Carbene/Transition Metal Catalysis.

N-heterocyclic carbene catalysis has been developed as a versatile method for the enantioselective synthesis of complex organic molecules in organic chemistry. Merging of N-heterocyclic carbene catalysis with transition metal catalysis holds the potential to achieve unprecedented transformations with broad substrate scope and excellent stereoselectivity, which are unfeasible with individual catalyst. Thus, this dual catalysis has attracted increasing attention, and numerous elegant dual catalytic systems have been established. In this review, we summarize the recent achievements of dual NHC/transition metal catalysis, including the reaction design, mechanistic studies and practical applications.

Base-Mediated Divergent Synthesis of Spiro-heterocycles Using Pronucleophiles and Ethylene via Thianthrenation.

Spirocyclic compounds are abundant in biologically active products. However, the divergent synthesis of spirocyclic compounds using low-cost and abundant available starting materials remains a challenge. Herein, we report an effective method for producing spirocyclic motifs using a cyclic ß-carbonyl ester or amide and ethylene via thianthrenation. This strategy highlights the exciting possibility of utilizing abundant ethylene as a C-2 synthon and allows regulating the core structure of the spirocyclic compound by simply altering the base type.

Highly efficient method for cutting position selection of an x-ray mono-capillary lens based on an improved SCA-CSA algorithm.

In order to efficiently select the optimal cutting position of x-ray mono-capillary lenses, an improved sine cosine algorithm-crow search algorithm (SCA-CSA) algorithm is proposed, which combines the sine cosine algorithm with the crow search algorithm, with further enhancements. The fabricated capillary profile is measured using an optical profiler; then the surface figure error for interest regions of the mono-capillary can be evaluated using the improved SCA-CSA algorithm. The experimental results indicate that the surface figure error in the final capillary cut region is about 0.138 µm, and the runtime is 2.284 s. When compared with the traditional metaheuristic algorithm, the particle swarm optimization algorithm, the improved SCA-CSA algorithm, enhances the surface figure error metric by two orders of magnitude. Furthermore, the standard deviation index of the surface figure error metric for 30 runs also improves by more than 10 orders of magnitude, demonstrating the superior performance and robustness of the algorithm. The proposed method provides significant support for the development of precise cuttings of mono-capillaries.

Semi-heterogeneous photo-Cu-dual-catalytic cross-coupling reactions using polymeric carbon nitrides.

A merger of copper catalysis and semiconductor photocatalysis using polymeric carbon nitride (PCN) for multi-type cross-coupling reactions was developed. This dual-catalytic system enables mild C-H arylation, chalcogenation, and C-N cross-coupling reactions under visible light irradiation with a broad substrate scope. Good-to-excellent yields were obtained with appreciable site selectivity and functional group tolerance. Metal-free and low-cost PCN photocatalyst can easily be recovered and reused several times.

Icariin regulates stem cell migration for endogenous repair of intervertebral disc degeneration by increasing the expression of chemotactic cytokines.

BACKGROUND: Icariin (ICA) can promote the migration and bone formation of bone marrow mesenchymal stem cells. This study explored a potential role of ICA in recruiting stem cell niches (SCNs) within the intervertebral disc region (ISN)-derived stem cells (ISN-SCs) to treat intervertebral disc degeneration (IVDD). MATERIALS AND METHODS: EdU staining, transwell, and wound healing tests were used to analyze the function of ICA on ISN-SCs proliferation and migration ability. Simultaneously, the IVDD rat model was constructed by the acupuncture and divided into Sham, Sham + ICA, IVDD, and IVDD + ICA groups. H&E and PAS staining were performed to detect the pathological changes of IVDD tissues. Immunofluorescence was performed to discover relevant marker expression on the surface of stem cells in the IVDD tissues. Western blot and qPCR were executed to find the protein and mRNA expression of related cytokines in the IVDD tissues. RESULTS: ISN-SCs treated with 1 µM ICA obtained the better ability of proliferation and migration. H&E staining showed that the annulus fibrosus in the IVDD group was obviously hyperplasia with cavities and fissures; the nucleus pulposus was reduced. PAS staining showed that the content of polysaccharides was significantly reduced in the nucleus pulposus of IVDD group. However, the ICA treatment alleviated the pathological trends of the IVDD tissues. Simultaneously, ICA treatment increased significantly the expression of stem cells and IGF-1, TGF-ß, SDF-1, CCL-5, Collagen I, Collagen II, Aggrecan, and SOX9 in IVDD tissues. CONCLUSIONS: ICA treatment promoted the migration of stem cell in IVDD by increasing the expression of chemotactic cytokines, including IGF-1, TGF-ß, SDF-1, and CCL-5.

Bioremediation of phenolic pollutants by algae - current status and challenges.

Industrial production processes, especially petroleum processing, will produce high concentration phenolic wastewater. Traditional wastewater treatment technology is costly and may lead to secondary pollution. In order to avoid the adverse effects of incompletely treated phenolics, more advanced methods are required. Algae bioremediate phenolics through green pathways such as adsorption, bioaccumulation, biodegradation, and photodegradation. At the same time, the natural carbon fixation capacity of algae and its potential to produce high-value products make algal wastewater treatment technology economically feasible. This paper reviews the environmental impact of several types of phenolic pollutants in wastewater and different strategies to improve bioremediation efficiency. This paper focuses on the progress of algae removing phenols by different mechanisms and the potential of algae biomass for further biofuel production. This technology holds great promise, but more research on practical wastewater treatment at an industrial scale is needed in the future.

Enhancement of Hydrothermal Stability and CO2 Adsorption of Mg-MOF-74/MCF Composites.

Hierarchical porous composite Mg-MOF-74/MCFs were successfully synthesized using a simple and facile method under in situ solvothermal conditions. Textural structures and morphologies of the composites were characterized by X-ray diffraction (XRD), N2 adsorption-desorption isotherms, and scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). The results demonstrate that a large amount of nanosized Mg-MOF-74 particles is incorporated into the pores of mesocellular siliceous foams (MCFs) without remarkable aggregation and the composites possess microporous and mesoporous characteristics of both components. In addition, CO2 adsorption properties of the composites were tested in a fixed bed with/without hydrothermal treatment. The total CO2 adsorption capacities were calculated by breakthrough curves. The CO2 adsorption capacity of the composites reaches 1.68 mmol/g, which is smaller than that of pristine Mg-MOF-74. However, the total CO2 adsorption capacity of the composites after hydrothermal treatment reaches 2.66 mmol/g, which is larger than that of Mg-MOF-74 (2.39 mmol/g) under the same condition. XRD patterns and SEM images of the composites demonstrate that the hydrothermal stability and CO2 adsorption performance of the composites were improved compared with those of pristine Mg-MOF-74 after hydrothermal treatment.

Photocatalytic Water-Splitting Coupled with Alkanol Oxidation for Selective N-alkylation Reactions over Carbon Nitride.

Photocatalytic water splitting technology (PWST) enables the direct use of water as appealing "liquid hydrogen source" for transfer hydrogenation reactions. Currently, the development of PWST-based transfer hydrogenations is still in an embryonic stage. Previous reports generally centered on the rational utilization of the in situ generated H-source (electrons) for hydrogenations, in which photogenerated holes were quenched by sacrificial reagents. Herein, the fully-utilization of the liquid H-source and holes during water splitting is presented for photo-reductive N-alkylation of nitro-aromatic compounds. In this integrate system, H-species in situ generated from water splitting were designed for nitroarenes reduction to produce amines, while alkanols were oxidized by holes for cascade alkylating of anilines as well as the generated secondary amines. More than 50 examples achieved with a broad range scope validate the universal applicability of this mild and sustainable coupling approach. The synthetic utility of this protocol was further demonstrated by the synthesis of existing pharmaceuticals via selective N-alkylation of amines. This strategy based on the sustainable water splitting technology highlights a significant and promising route for selective synthesis of valuable N-alkylated fine chemicals and pharmaceuticals from nitroarenes and amines with water and alkanols.

Electrocatalytic water-splitting for the controllable and sustainable synthesis of deuterated chemicals.

Tandem water electrolysis for the transformation of universal feedstock to value-added chemicals integrated with hydrogen generation and in situ utilization is a promising approach to address the economic challenges of electrochemical hydrogen evolution and storage. Herein, we present the controllable electrocatalytic deuteration of halides using inexpensive and reusable heavy water (D2O) as a D-source for the preparation of valuable D-labelled chemicals and pharmaceuticals under mild conditions. This electrochemical deuteration method with high efficiency and selectivity furnishes a series of D-labelled chemicals and pharmaceuticals in high yields with excellent D-incorporation. The reaction efficiency and selectivity, that is, the precise substitution of deuterium atoms at different halogen positions, can be tuned by varying the applied voltages. The results show the great potential of green and economical electrocatalytic methods for producing value-added fine chemicals in addition to hydrogen evolution.

How the clinical dosage of bone cement biomechanically affects adjacent vertebrae.

OBJECTIVE: This study evaluated the biomechanical changes in the adjacent vertebrae under a physiological load (500 N) when the clinically relevant amount of bone cement was injected into fractured cadaver vertebral bodies. METHODS: The embalmed cadaver thoracolumbar specimens in which each vertebral body (T12-L2) had a BMD of < 0.75 g/cm2 were used for the experiment. For establishing a fracture model, the upper one third of the L1 vertebra was performed wedge osteotomy and the superior endplate was kept complete. Stiffness of specimens was measured in different states. Strain of the adjacent vertebral body and intervertebral disc were measured in pre-fracture, post-fracture, and after augmentation by non-contact optical strain measurement system. RESULTS: The average amount of bone cement was 4.4 ml (3.8-5.0 ml). The stiffness of after augmentation was significantly higher than the stiffness of post-fracture (p < 0.05), but still lower than pre-fracture stiffness (p < 0.05). After augmentation, the adjacent upper vertebral strain showed no significant difference (p > 0.05) with pre-fracture, while the strain of adjacent lower vertebral body was significantly higher than that before fracture (p < 0.05). In flexion, T12/L1 intervertebral disc strain was significantly greater after augmentation than after the fracture (p < 0.05), but there was no significant difference from that before the fracture (p > 0.05); L1/2 vertebral strain after augmentation was significantly less than that after the fracture (p < 0.05), but there was no significant difference from that before the fracture (p > 0.05). CONCLUSIONS: PVP may therefore have partially reversed the abnormal strain state of adjacent vertebral bodies which was caused by fracture.

Semiconductor photocatalysis to engineering deuterated N-alkyl pharmaceuticals enabled by synergistic activation of water and alkanols.

Precisely controlled deuterium labeling at specific sites of N-alkyl drugs is crucial in drug-development as over 50% of the top-selling drugs contain N-alkyl groups, in which it is very challenging to selectively replace protons with deuterium atoms. With the goal of achieving controllable isotope-labeling in N-alkylated amines, we herein rationally design photocatalytic water-splitting to furnish [H] or [D] and isotope alkanol-oxidation by photoexcited electron-hole pairs on a polymeric semiconductor. The controlled installation of N-CH3, -CDH2, -CD2H, -CD3, and -13CH3 groups into pharmaceutical amines thus has been demonstrated by tuning isotopic water and methanol. More than 50 examples with a wide range of functionalities are presented, demonstrating the universal applicability and mildness of this strategy. Gram-scale production has been realized, paving the way for the practical photosynthesis of pharmaceuticals.

Evaluation of the analgesic effect of vertebral cancellous bone infiltration anaesthesia during vertebroplasty.

OBJECTIVE: To evaluate the analgesic effect of vertebral cancellous bone infiltration anaesthesia during percutaneous vertebroplasty (PVP). METHODS: Patients treated with vertebral cancellous bone infiltration anaesthesia (intervention group) or local anaesthesia alone (control group) during PVP at our institution during 2016-2018 were reviewed. The visual analogue scale (VAS) score before the operation, during establishment of the puncture channel, during pressure changes in the vertebral body (e.g., when removing or inserting pushers or needle cores), during bone cement injection, immediately after the operation, and at 2 h and 1 day postoperatively were compared between the groups. The patient's satisfaction with the operation was recorded and compared between groups. RESULTS: A total of 112 patients were enrolled (59 cases in the intervention group and 53 cases in the control group). There was no difference in the VAS score between the groups before the operation or during establishment of the intraoperative puncture channel (P > 0.05). The VAS score in the intervention group was significantly lower than that in the control group during pressure changes in the vertebral body (removal or insertion of puncture needle cores or pushers) and bone cement injection (P < 0.05). Immediately after the operation and at 2 h postoperatively, the pain in the intervention group was also significantly lower than that in the control group (P < 0.05), but there was no significant difference between the groups at 1 day postoperatively (P > 0.05). The patient satisfaction rate was 88% (52/59) in the intervention group and 67% (35/53) in the control group (P < 0.05). CONCLUSIONS: Vertebral cancellous bone infiltration anaesthesia may effectively relieve intraoperative pain and improve the surgical experience of patients without affecting the clinical effect of surgery.

Icariin protects rabbit BMSCs against OGD-induced apoptosis by inhibiting ERs-mediated autophagy via MAPK signaling pathway.

Stem cell therapy is widely employed in treating osteoarthritis (OA), and bone marrow-derived mesenchymal stem cells (BMSCs) has gradually become the most attractive new method for treating OA due to the benefit for cartilage tissue repair. However, the apoptosis in the neural stem cell transplantation severely decreases repairing efficacy. Icariin has been reported to exert multiple effects on BMSCs, including its proliferation, osteogenic, and chondrogenic differentiation. However, its effects on the injury induced by oxygen, glucose and serum deprivation (OGD) remains unknown. We prospectively investigated the role of ICA on rabbit BMSCs under conditions of OGD. Firstly, BMSCs were cultured under conditions of OGD, ICA relieved OGD-induced cell damage by promoting cell proliferation and suppressing apoptosis. Secondly, Markers of endoplasmic reticulum stress (ERs), ER stress IRE-1 pathway, and autophagy were both inhibited by ICA via inhibition of phosphor-extracellular regulated protein kinases (p-ERKs), p-P38, p-c-Jun N-terminal kinase (p-JNK) or si-MAPK. Finally, decrease of ERs marker levels enhanced protective effect of ICA against OGD-induced injury by limiting apoptosis and autophagy. Moreover, an autophagy inhibitor (3-methyladenine: 3-MA) contributed to a synergistic effect in conjunction with ICA, in promoting cell proliferation, suggesting that ICA exerts anti-ERs and anti-autophagy effects in OGD-treated BMSCs. Therefore, ICA protected rabbit BMSCs from OGD-induced apoptosis through inhibitory regulation of ERs-mediated autophagy related to the MAPK signaling pathway, which provided insights for a potential therapeutic strategy in OA.

Effect of time to first ambulation on recurrence after PELD.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the effect of time to first ambulation on recurrence after percutaneous endoscopic lumbar discectomy (PELD). METHODS: From July 2017 to August 2018, 90 patients with lumbar intervertebral disc herniation underwent PELD surgery. According to the initial walking time, i.e., the time until the patient could walk after the operation, the operations were divided into three groups: early stage, middle stage, and late stage. The follow-up period was 3 months, and complete follow-up data were obtained. The visual analog scale (VAS) and Oswestry disability index (ODI) scores before the operation, at first ambulation, 1 month after the operation, and 3 months after the operation and the recurrence and incidence rates of high magnetic resonance imaging (MRI) signal in the vertebral endplate area were recorded after the operation. RESULTS: The success rate was 100% for these 90 cases. The VAS and ODI scores at the first ambulation after the operation significantly improved compared with those before the operation, and the difference was statistically significant. The improvements in the lumbar VAS and ODI scores of the middle- and late-stage groups were better than that of the early-stage group at 1 and 3 months after the operation, and the differences were statistically significant; however, there was no significant difference between the middle- and late-stage groups. The postoperative recurrence rate and rate of high MRI signal in the vertebral endplate area were significantly higher in the early-stage group than in the other two groups, and the difference was statistically significant. CONCLUSION: The time to first ambulation after PELD is an important factor affecting the curative effect of the operation. Early ambulation may be one of the factors affecting recurrence after PELD.

A second puncture and injection technique for treating osteoporotic vertebral compression fractures.

OBJECTIVE: To evaluate the clinical effect of the second puncture and injection technique during a percutaneous vertebroplasty (PVP) procedure. METHODS: Patients treated with a second puncture and injection (group A) or a single puncture and injection (group B) during PVP at our institution during 2010-2017 were reviewed. Vertebral height loss, visual analogue scale (VAS) score, Oswestry disability index (ODI), adjacent vertebral fractures, and cement leakage were compared between the groups. RESULTS: A total of 193 patients were enrolled (86 cases in group A, 107 cases in group B). The follow-up period was 15.64 (12-20) months. The loss of anterior (group A 0.01 ± 0.03; group B 0.14 ± 0.17) and middle (group A 0.13 ± 0.12; group B 0.16 ± 0.11) vertebral height in group B was significantly higher than that in group A (P < 0.05). The VAS score and ODI were also significantly higher in group B than in group A at the final follow-up; the VAS score and ODI in group B were 1.65 ± 0.70 and 14.50 ± 4.16, respectively, and those in group A were 1.00 ± 0.74 and 12.81 ± 4.02, respectively (P < 0.05). Three patients in group A and two in group B experienced adjacent vertebral fractures. Regarding mild, moderate, and severe cement leakage, there were 25 (29%), 5 (5%), and 0 cases, respectively, in group A and 28 (26%), 3 (2.8%), and 1 (0.009%) case, respectively, in group B (P > 0.05). CONCLUSIONS: The second puncture and injection technique may effectively increase the dispersion of cement, thus preventing recompression of the cemented vertebral body, and it does not increase the risk of cement leakage or adjacent vertebral fracture.

The mechanism of TDP-43 gene expression on inflammatory factors and the JNK and p38 MAPK signalling pathways in ischaemic hypoxic stress dependence.

In this study, the mechanism of TDP-43 gene expression on inflammatory factors and Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signalling pathways in ischaemic hypoxic stress dependence was investigated. Sixty SD rats were selected and divided into the control group, the osteoarthritis (OA) model group, and the TDP-43-mMSCs+OA group. In the OA model group and the TDP-43-mMSCs+OA group, OA was established by collagenase injection. Western blotting assays were used to detect the expression of TDP-43 in cartilage tissues of each rat. The secretion of tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in the serum of rats was determined by enzyme-linked immunosorbent assay (ELISA). The formation of cytoplasmic stress granules (SGs) and the expression of receptor for activated c-kinase 1 (RACK1) were detected by Western blotting assays in each group of rats. The expression of MTK1 and MAPKKK phosphorylation and changes in the JNK and p38 MAPK signalling pathways were detected by Western blotting assays. Compared with the control group, the expression of TDP-43 in the cartilage tissue of rats in the OA model group was significantly decreased. The expression of TDP-43 in the cartilage tissue of rats in the TDP-43-mMSCs+OA group was significantly higher than that of the control group and the OA model group, which indicates that TDP-43-mMSC transplantation was successful. Enzyme-linked immunosorbent assay results showed that the plasma TNF-α and IL-1ß levels in the OA model group were significantly increased (P < 0.01) when compared with the control group. However, the secretion of TNF-α and IL-1ß in the serum of the TDP-43-mMSCs+OA group was significantly lower than that of the model group (P < 0.01) but still higher than the control group. This indicates that overexpression of TDP-43 reduces the inflammatory response induced by OA. Western blotting assays showed that the amount of cytoplasmic SGs in the cartilage tissue of rats in the OA model group was significantly decreased when compared with the control group. The amount of SGs in the cartilage of rats in the TDP-43-mMSCs+OA group was significantly higher than that of the model group. The expression of RACK1 in the cartilage tissue of rats in the OA model group was significantly higher than that of the control group. Overexpression of the TDP-43 gene can interfere with the secretion of inflammatory factors and inhibit the activation of the JNK and p38 MAPK signalling pathways by ischaemic hypoxia stress. Thus, the molecular mechanism of chondrocytopathic lesions was reversed, which provided a new theoretical basis for the treatment of OA.

Icariin inhibits chondrocyte apoptosis and angiogenesis by regulating the TDP-43 signaling pathway.

BACKGROUND: This study focused on the mechanisms where icariin inhibited chondrocyte apoptosis and angiogenesis by regulating the TDP-43 signaling pathway. METHODS: A rat osteoarthritis (OA) model was established by collagenase injection. Histological examination of the articular cartilage and synovial tissue was performed 6 weeks after operation. Cartilage cell line overexpressing TDP-43 and mesenchymal stem cell line (TDP43-MSCs) of the rat TDP43 gene were established. RESULTS: In OA rats transplanted with TDP43-mMSCs, TDP43 was highly expressed in chondrocytes (TDP43-HC), while TDP43 expression was low in HC and MSCs-HC (p < 0.05). After the intervention of MSCs-TDP43, high expression of TDP43 induced the apoptosis and death of chondrocytes. After the addition of icariin, late apoptosis and death of TDP43-HC were significantly attenuated. Apoptosis and death of HC, MSCs-HC, and TDP43-HC cells were effectively controlled with icariin, and no apparent cell death was found. ELISA showed that the VEGF and HIF-1 alpha were significantly higher in the rat OA model than the normal control rats. CONCLUSION: TDP43-MSC transplantation interfered with the expression of TDP43 in the articular chondrocytes of OA rats, which may impact on inducing apoptosis of chondrocytes as well as inhibiting the proliferation of chondrocytes. Additionally, TDP43-MSCs appeared to promote the formation of neovascularization in the synovial tissue, which could be significantly attenuated by icariin.

Icariin Promotes the Migration of BMSCs In Vitro and In Vivo via the MAPK Signaling Pathway.

Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used in tissue engineering for regenerative medicine due to their multipotent differentiation potential. However, their poor migration ability limits repair effects. Icariin (ICA), a major component of the Chinese medical herb Herba Epimedii, has been reported to accelerate the proliferation, osteogenic, and chondrogenic differentiation of BMSCs. However, it remains unknown whether ICA can enhance BMSC migration, and the possible underlying mechanisms need to be elucidated. In this study, we found that ICA significantly increased the migration capacity of BMSCs, with an optimal concentration of 1 µmol/L. Moreover, we found that ICA stimulated actin stress fiber formation in BMSCs. Our work revealed that activation of the MAPK signaling pathway was required for ICA-induced migration and actin stress fiber formation. In vivo, ICA promoted the recruitment of BMSCs to the cartilage defect region. Taken together, these results show that ICA promotes BMSC migration in vivo and in vitro by inducing actin stress fiber formation via the MAPK signaling pathway. Thus, combined administration of ICA with BMSCs has great potential in cartilage defect therapy.

DBU-Mediated Construction of 1,3,5-Trisubstituted Benzenes via Annulation of α,ß-Unsaturated Carboxylic Acids and α-Cyano-ß-methylenones.

A DBU-mediated synthesis of 1,3,5-trisubstituted benzenes was developed via the [2 + 4] annulation of in situ activated α,ß-unsaturated carboxylic acids and α-cyano-ß-methylenones. The dual role of DBU as Brønsted base and nucleophilic Lewis base is the key for the success of the reaction.