Directing group migration strategy in transition-metal-catalysed direct C-H functionalization.

Very recently, directing group (DG) migration has emerged as a practical strategy for transition-metal-catalysed direct C-H activation, resulting in a highly atom-economical process and enabling the reusage of DG. Therefore, great progress has been made in developing multitasking DGs. In this tutorial review, we present the rapid advances of this novel strategy by analyzing and comparing the different types of migratable DGs (including N-O, N-C, N-N or O-C bond cleavage to trigger DG migration). The related mechanisms, as well as synthetic applications, are also mentioned.

Synthesis of Axially Chiral Aldehydes by N-Heterocyclic-Carbene-Catalyzed Desymmetrization Followed by Kinetic Resolution.

Axially chiral aldehydes have received increasing attention in enantioselective catalysis. However, only very few catalytic methods have been developed to construct structurally diverse axially chiral aldehydes. We herein describe an NHC-catalyzed atroposelective esterification of biaryl dialdehydes as a general and practical strategy for the construction of axially chiral aldehydes. Mechanistic studies indicate that coupling proceeds through a novel combination of NHC-catalyzed desymmetrization of the dialdehydes and kinetic resolution. This protocol features excellent enantioselectivity, mild conditions, good functional-group tolerance, and applicability to late-stage functionalization and provides a modular platform for the synthesis of axially chiral aldehydes and their derivatives.

Synthesis of axially chiral diaryl ethers via NHC-catalyzed atroposelective esterification.

Axially chiral diaryl ethers bearing two potential axes find unique applications in bioactive molecules and catalysis. However, only very few catalytic methods have been developed to construct structurally diverse diaryl ethers. We herein describe an NHC-catalyzed atroposelective esterification of prochiral dialdehydes, leading to the construction of enantioenriched axially chiral diaryl ethers. Mechanistic studies indicate that the matched kinetic resolutions play an essential role in the challenging chiral induction of flexible dual-axial chirality by removing minor enantiomers via over-functionalization. This protocol features mild conditions, excellent enantioselectivity, broad substrate scope, and applicability to late-stage functionalization, and provides a modular platform for the synthesis of axially chiral diaryl ethers and their derivatives.

PSO/SDF-1 composite hydrogel promotes osteogenic differentiation of PDLSCs and bone regeneration in periodontitis rats.

Periodontitis is an inflammatory disease characterized by the destruction of periodontal tissues, and the promotion of bone tissue regeneration is the key to curing periodontitis. Psoralen is the main component of Psoralea corylifolia Linn, and has multiple biological effects, including anti-osteoporosis and osteogenesis. We constructed a novel hydrogel loaded with psoralen (PSO) and stromal cell-derived factor-1 (SDF-1) for direct endogenous cell homing. This study aimed to evaluate the synergistic effects of PSO/SDF-1 on periodontal bone regeneration in patients with periodontitis. The results of CCK8, alkaline phosphatase (ALP) activity assay, and Alizarin Red staining showed that PSO/SDF-1 combination treatment promoted cell proliferation, chemotaxis ability, and ALP activity of PDLSCs. qRT-PCR and western blotting showed that the expression levels of alkaline phosphatase (ALP), dwarf-associated transcription factor 2 (RUNX2), and osteocalcin (OCN) gene were upregulated. Rat periodontal models were established to observe the effect of local application of the composite hydrogel on bone regeneration. These results proved that the PSO/SDF-1 combination treatment significantly promoted new bone formation. The immunohistochemical (IHC) results confirmed the elevated expression of ALP, RUNX2, and OCN osteogenic genes. PSO/SDF-1 composite hydrogel can synergistically regulate the biological function and promote periodontal bone formation. Thus, this study provides a novel strategy for periodontal bone regeneration.

Osteogenesis promotion by injectable methacryloylated gelatin containing psoralen and its bacteriostatic properties.

The treatment of periodontitis focuses on controlling the progression of inflammation, reducing plaque accumulation, and promoting bone tissue reconstruction. Among them, the reconstruction of irregular bone resorption caused by periodontitis is a long-standing challenge. At present, the local drug treatment of periodontitis is mainly anti-inflammatory and antibacterial drugs. In this study, psoralen (Pso), a Chinese herbal medicine with anti-inflammatory, antibacterial, and osteogenic effects, was selected for the local treatment of periodontitis. Meanwhile, an injectable methacrylate gelatin (GelMA) platform loading with Pso was constructed. Pso-GelMA had the properties of fluidity, light cohesion, self-healing, and slow release, which could be better used in the deep and narrow structure of the periodontal pocket, and greatly increased the effectiveness of local drug delivery. The pore size of Gelma hydrogel did not change after loading Pso by SEM. In vitro, Pso-GelMA effectively upregulated the expression of osteogenic genes and proteins, increased alkaline phosphatase activity, promoted the mineralisation of rat bone marrow mesenchymal stem cells (BMSCs) extracellular matrix, and had significant antibacterial effects on Staphylococcus aureus and Fusobacterium nucleatum. Therefore, Pso-GelMA has immense promise in the adjuvant treatment of periodontitis.

Effect of psoralen on the regulation of osteogenic differentiation induced by periodontal stem cell-derived exosomes.

Periodontitis is a chronic inflammatory disease that is the main cause of tooth loss in adults, and the key to periodontitis treatment is the repair and regenerate of periodontal bone tissue. Psoralen is the main component of the Psoralea corylifolia Linn, which shows antibacterial, anti-inflammatoryand osteogenic activities. It promotes the differentiation of periodontal ligament stem cells toward osteogenesis. Exosomes secreted by stem cells play important roles in information transmission during the osteogenic differentiation process. The aim of this paper was to investigate the role of psoralen in regulating osteogenic miRNA information in periodontal stem cells and in periodontal stem cells exosomes and the specific mechanism of its action. Experimental results show that exosomes of human periodontal ligament stem cell origin treated with psoralen (hPDLSCs + Pso-Exos) were not significantly different from untreated exosomes (hPDLSC-Exos) in terms of size and morphology. Thirty-five differentially expressed miRNAs were found to be upregulated and 58 differentially expressed miRNAs were found to be downregulated in the hPDLSCs + Pso-Exos compared to the hPDLSC-Exos (P < 0.05). hsa-miR-125b-5p was associated with osteogenic differentiation. Among them, hsa-miR-125b-5p was associated with osteogenic differentiation. After hsa-miR-125b-5p was inhibited, the osteogenesis level of hPDLSCs was enhanced. In summary, the osteogenic differentiation of hPDLSCs was promoted by psoralen through the downregulation of hsa-miR-125b-5p gene expression in hPDLSCs, and the expression of the hsa-miR-125b-5p gene was also downregulated in exosomes. This finding provides a new therapeutic idea for using psoralen to promote periodontal tissue regeneration.

Multiomics analysis of metabolic heterogeneity in cervical cancer cell lines with or without HPV.

Metabolomics analysis revealed the metabolic heterogeneity of cervical cancer (CC) cell lines C33A and CaSki, and their molecular mechanisms were explored. Using the modified Bligh-Dyer method, the endogenous metabolites of C33A and CaSki cells were divided into polar and nonpolar fractions. The metabolites were analysed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Then, the differential metabolites were screened by combining multivariate statistical analysis and volcano maps, and functional enrichment and pathway analysis of the differential metabolites were performed. Finally, association analysis was carried out in combination with transcriptomics, and the important differential metabolisms were experimentally verified by real-time PCR (RT-qPCR) and oil red staining. The results showed that between the C33A and CaSki cell lines, there were significant differences in amino acids, nucleotides and lipids, such as in threonine, arachidonic acid and hypoxanthine, in the metabolic pathways. These compounds could be used as markers of differences in cellular metabolism. The heterogeneity of lipid metabolism accounted for 87.8%, among which C33A cells exhibited higher contents of fatty acid polar derivatives, while CaSki cells showed higher contents of free fatty acids and glycerides. Based on correlation analysis of the above metabolic differences in HPV pathways as well as lipid metabolism-related genes, p53 and the genes involved in lipid metabolism pathways, such as Peroxisome Proliferator Activated Receptor Gamma(PPARG) and stearoyl-CoA desaturase (SCD), are relevant to the metabolic heterogeneity of the cells. The differential expression of some genes was validated by RT-qPCR. CaSki cells showed significantly higher glyceride levels than that of C33A cells, as verified by oil red O staining and glyceride assays. The above results showed that the metabolomic differences between C33A and CaSki cells were relatively obvious, especially in lipid metabolism, which might be related to the decreased expression of PPARG and p53 caused by HPV E6. Further studies on the molecular mechanism of lipid metabolism heterogeneity in cervical cancer cell lines with or without HPV could provide a new reference for the development of CC and individualized treatments of tumour patients.

The Temporal and Spatial Distributions and Influencing Factors of Transboundary Pollution in China.

Transboundary pollution between neighboring regions seriously affects the efficiency of overall environmental governance; however, there are few studies focused on how to estimate the degree of transboundary pollution between different regions. With China as a case study, this article developed a new measurement to estimate the degree of transboundary pollution among regions, and comprehensively investigated the influencing factors of transboundary pollution in China between 2000 and 2013. The results indicate that transboundary pollution effects exist in China. In ascending order, the regions most affected overall by transboundary pollution from polluting enterprises were as follows: eastern region < central region < western region. The reduction in transboundary pollution effects was most prominent for severely polluting enterprises in the eastern and western regions and lightly polluting enterprises in the central region. An analysis of the influencing factors reveals that the regional environmental regulation intensity has a negative feedback effect on the transboundary pollution effects. These findings indicate that polluting enterprises in regions with a low environmental regulation intensity are more inclined to operate in border areas to obtain both the environmental benefits associated with the low local environmental regulation intensity and the market economy benefits associated with neighboring urban regions, thereby aggravating environmental pollution in border areas.

Influence of periodontal treatment on blood microbiotas: a clinical trial.

OBJECTIVE: To investigate the effects of periodontal treatment on the abundance and diversity of blood microbiota. METHODS AND MATERIALS: Twenty-seven periodontitis patients were randomly allocated to a control group (A) and two test groups (B1 and B2). Group A patients received full-mouth scaling and root planing (SRP), group B1 patients received subgingival glycine air polishing (GAP) right after SRP, and group B2 patients received subgingival glycine air polishing right before SRP. Peripheral blood samples were obtained at the baseline, the day after periodontal treatment, and 6 weeks after treatment and evaluated using nested polymerase chain reaction and 16SrRNA Gene Sequencing (Miseq platform). RESULTS: All participants exhibited significant improvements in the clinical parameters evaluated at the 6-week follow-up visit compared to the values at the baseline, but no significant differences were observed between the three groups. The total bacterial count was lowest in group B2. The bacterial species diversity (α-diversity) in group B1 was significantly higher (Chao-1 index, P = 0.03) and Porphyromonas and Pantoea were the dominant genera (linear discriminant analysis (LDA > 2)) in this group the day after treatment compared to the baseline. No significant difference was detected in the relative abundance and α-diversity of blood microbiota between the baseline and 6 weeks after treatment. CONCLUSION: Local periodontal treatment merely disrupts the stability of blood microbiota in the short term. Periodontitis treatment using full-mouth SRP followed by adjunctive GAP is a promising approach to reduce the introduction of bacteria into the bloodstream during the procedure.

Effect of Psoralen on the Intestinal Barrier and Alveolar Bone Loss in Rats With Chronic Periodontitis.

To study the effects of psoralen on the intestinal barrier and alveolar bone loss (ABL) in rats with chronic periodontitis. Fifty-two 8-week-old specific pathogen-free (SPF) male Sprague-Dawley (SD) rats were randomly divided into the following four groups: Control group (Control), psoralen group of healthy rats (Pso), periodontitis model group (Model), and psoralen group of periodontitis rats (Peri+Pso). The alveolar bone resorption of maxillary molars was observed via haematoxylin-eosin staining and micro-computed tomography. The expression level of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in periodontal tissues was evaluated by immunofluorescence staining. The changes in serum tumour necrosis factor (TNF)-α, interleukin (IL)-10, IL-6, intestinal mucosal occludin, and claudin-5 were detected using enzyme-linked immunosorbent assay (ELISA). The level of intestinal mucosal NOD2 was detected using immunohistochemical methods. DNA was extracted from the intestinal contents and the 16s rRNA gene was sequenced using an Illumina MiSeq platform. The expression of NOD2 protein in the intestinal tract of periodontitis rats decreased after intragastric psoralen administration. Psoralen increased the intestinal microbiota diversity of rats. The level of serum pro-inflammatory factor TNF-α decreased and the level of anti-inflammatory factor IL-10 increased. ABL was observed to be significantly decreased in rats treated with psoralen. Psoralen decreased the RANKL/OPG ratio of periodontitis rats. Psoralen may affect the intestinal immune barrier and ecological barrier, mediate immune response, promote the secretion of anti-inflammatory factor IL-10, and reduce the secretion of the pro-inflammatory factor TNF-α, thus reducing ABL in experimental periodontitis in rats.

[Expression of SFRP1 and MIF in elderly patients with severe periodontitis and its correlation with cognitive function].

PURPOSE: To investigate the expression of secreted frizzle-related protein 1 (SFRP1) and macrophage migration inhibitory factor (MIF) in elderly patients with severe periodontitis and its correlation with cognitive function. METHODS: Thirty-two elderly patients with periodontitis in Qingdao Stomatological Hospital from February 2018 to February 2019 were enrolled, and divided into two groups according to the severity: mild group and severe group. All selected subjects received periodontal examination and Montreal cognitive assessment (MoCA).The expression of SFRP1 and MIF in serum was also determined. Then the correlations among SFRP1 and MIF periodontal index and cognitive function was analyzed. The data were processed by SPSS 20.0 software package. RESULTS: The probing depth (PD), clinical attachment level (CAL), sulcus bleeding index (SBI) and gingival crevicular fluid (GCF) showed significant difference between the two groups (P<0.05). The serum levels of SFRP1 and MIF in the severe group were significantly higher than those in the mild group (P<0.05). Serum SFRP1 level was positively correlated with MIF (P<0.05). Serum SFRP1 and MIF levels were positively correlated with periodontal index (P<0.05). The MoCA score of the severe group was significantly lower than that of the mild group (P<0.05). Serum SFRP1 and MIF levels were negatively correlated with MoCA score (P<0.05). CONCLUSIONS: SFRP1 and MIF are highly expressed in serum and gingival tissues of elderly patients with severe periodontitis, and are closely related to the degree of periodontal damage. Meanwhile, patients with periodontitis may have some degree of cognitive dysfunction, and SFRP1 and MIF may affect the periodontal tissue structure through Wnt/ß-catenin signal pathway and participate in the occurrence and development of cognitive dysfunction.

Rh(III)-Catalyzed Tandem Acylmethylation/Nitroso Migration/Cyclization of N-Nitrosoanilines with Sulfoxonium Ylides in One Pot: Approach to 3-Nitrosoindoles.

A novel synthesis of 3-nitrosoindoles starting from easily available N-nitrosoanilines and sulfoxonium ylides via Rh(III)-catalyzed acylmethylation and trifluoroacetic acid (TFA)-mediated nitroso transfer/cyclization cascade reaction in one pot has been developed. The N-nitroso group plays a dual role as a versatile directing group and internal nitrosation reagent. Rh(III)-catalyzed C-H activation/C-C bond formation and TFA-mediated N-N bond cleavage/formation of two C-N bonds are involved in this reaction. This process is scalable and avoids external oxidation. DMSO and H2O are produced as byproducts. Moreover, further chemical transformations of the desired products enhance its synthetic value.

Study on the Role of Salivary Flora and NF-κB Inflammatory Signal Pathway in Oral Lichen Planus.

Oral lichen planus (OLP) is an inflammatory disease. It is believed that infection and immune dysfunction play a key role in its pathogenesis, but the specific mechanism of action remains unclear. The 16s rRNA high-throughput sequencing technique was used to analyze the microbial flora structure in the saliva of OLP patients and healthy controls. The relative abundance of Derxia, Haemophilus, and Pseudomonas in the saliva of the OLP group was lower than that of the healthy control group, but there was no significant difference in the overall structure of the microbial population. In addition, we measured the protein expression levels of toll-like receptor 4 (TLR4) and nuclear factor-kappab p65 (NF-κB p65) in the tissues of OLP patients, and found that there was a significant increase and positive correlation between them (r = 0.907, P = 0.034). The expression levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the OLP group were consistent with those of NF-κB p65. Therefore, we believe that changes in the composition ratio of microbialflora break the original balance state of flora, promote the occurrence of immune inflammatory reaction, and then lead to the generation or aggravation of OLP disease. This discovery provides new ideas for further research on OLP initiation and immune regulation mechanism.

Auto-ignition behaviors of nitromethane in diluted oxygen in a rapid compression machine: Critical conditions for ignition, ignition delay times measurements, and kinetic modeling interpretation.

In this work, the weakest thermodynamic conditions for the auto-ignition of mixtures containing nitromethane were experimentally determined by using the rapid compression machine facility. Results show there is a narrow weak ignition region between ignition and non-ignition. The weak ignition region would disappear with the increase of the EOC (end of compression) pressure and nitromethane concentration. In addition, the ignition delay times for successful auto-ignition for different nitromethane concentrations and equivalence ratio mixtures were measured and compared. Results show that the dependence of nitromethane ignition on the equivalence ratio is weak. Subsequently, the measured ignition delay time data were employed to validate several kinetic models in literature and our previous model shows better agreement with experimental results, as well as other available literature data. Sensitivity analysis for the model reveals the importance of unimolecular decomposition and H-abstraction reactions for the ignition delay times in the temperature range studied herein. Finally, critical conditions for nitromethane ignition under extended conditions that are beyond the ability of the experimental facility were predicted.

Administration of probiotic mixture DM#1 ameliorated 5-fluorouracil-induced intestinal mucositis and dysbiosis in rats.

OBJECTIVE: The use of probiotics to alleviate chemotherapy-induced intestinal mucositis is supported by clinical consensus. However, no studies to date, to our knowledge, have systematically analyzed the effects of a probiotic mixture on chemotherapy-induced mucositis or assessed changes in the intestinal microbiota after probiotic treatment. The aim of this study was to report the effects of a probiotic mixture, DM#1, on intestinal mucositis and dysbiosis of rats treated with 5-fluorouracil (5-FU). METHODS: Twenty-eight male Sprague Dawley rats weighing 180 to 220 g were randomly divided into four groups: control, 5-FU, probiotic high (PH), and probiotic low (PL). Except for the control group, all other groups received intraperitoneal injections of 5-FU for 5 d, and the PH and PL groups received DM#1 intragastrically (1 × 109 or 1 × 108 colony-forming units/kg, respectively) for 8 d. One day after the last administration, rats were sacrificed and the ilea were removed for histopathologic assessment and evaluation of permeability, myeloperoxidase activity, levels of cytokines (interleukin [IL]-4, IL-6, tumor necrosis factor [TNF]-α), and mRNA of toll-like receptors (TLR; TLR2, TLR4, and TLR9). Additionally, intestinal microbiota profiles were analyzed by polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis and quantitative real-time PCR. RESULTS: Treatment with DM#1 ameliorated 5-FU-induced intestinal mucosal injury in rats, possibly by reducing proinflammatory cytokine levels and neutrophil infiltration. The increased intestinal permeability caused by 5-FU was ameliorated. These results were closely associated with the reestablishment of intestinal microbial homeostasis and alteration of the TLR2/TLR4 signaling pathway. CONCLUSIONS: Administration of the probiotic mixture DM#1 ameliorated 5-FU-induced intestinal mucositis and dysbiosis in rats.

Effect of ß-anhydroicaritin on the expression levels of tumor necrosis factor-α and matrix metalloproteinase-3 in periodontal tissue of diabetic rats.

The present study aimed to investigate the effect of ß-anhydroicaritin on the expression levels of tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-3, and the pathological changes in the periodontal tissue of diabetic rats. Male Wistar rats (n=40; three months old) were randomly divided into four groups: Normal control group, diabetes group, diabetes + ß-anhydroicaritin group and diabetes + urate group, (n=10 in each group). Following an overnight fast, diabetes was induced by intraperitoneal injection of streptozocin. The rats were maintained for 12 weeks and the blood sugar, urine sugar and body weight were assessed in week 12. Histological changes of the periodontal tissues were observed by hematoxylin and eosin staining, and the expression levels of TNF-α and MMP-3 were observed by immunohistochemistry. Following 12 weeks, the TNF-α grey value in the diabetes group was significantly lower compared with that in the control group (P<0.05), while no significant difference was observed between TNF-α levels in the diabetes + ß-anhydroicaritin group, diabetes + urate group and the control group (P>0.05). However, TNF-α levels in the diabetes + ß-anhdroicaritin group and diabetes + urate group were significantly higher compared with those in the diabetes group (P<0.05), and those in the diabetes + ß-anhydroicaritin group were lower compared with those in the diabetes + urate group (P<0.05). The MMP-3 grey value in the diabetes group was significantly lower compared with that in the control group (P<0.05), while no significant difference was observed between MMP-3 levels in the diabetes + ß-anhydroicaritin group, diabetes + urate group and the control group (P>0.05). However, MMP-3 levels the diabetes + ß-anhydroicaritin group and diabetes + urate group were significantly higher compared with those in the diabetes group (P<0.05), and those in the diabetes + ß-anhydroicaritin group were lower compared with those in the diabetes + urate group (P<0.01). ß-anhydroicaritin normalized the expression levels of TNF-α and MMP-3 in the periodontal tissue of diabetic rats and led to the recovery of the changes in the morphological structure of the periodontal tissue.

[Advances of clinical studies on acupuncture and moxibustion for treatment of periodontitis].

Periodontitis is a chronic inflammatory disease of multiple causes with easy relapse. It is difficult to be cured completely and permanently. The effectiveness of acupuncture and moxibustion therapy is rapid and reliably in treatment of pain and gingival swelling complicated by periodontitis. Combination of acupuncture and moxibustion with scaling, gargle had better effects in eliminating gingival inflammation, relieving periodontal packet and teeth mobility, which need to be confirmed by more clinical control researches with standard periodontal parameters and criteria of therapeutic effects.