Rhodium-catalyzed C-H carboxymethylation of anilines with vinylene carbonate.

A rhodium-catalyzed synthesis of phenylacetate has been realized by direct C-H carboxymethylation of anilines bearing removable directing groups. The reaction occurred most efficiently in air, without any external base or oxidant. This methodology is expected to provide a facile and general access to various bioactive 2-amino aromatic acetic acid derivatives.

Rhodium-Catalyzed Azine-Directed C-H Amidation with N-Methoxyamides.

Using N-methoxyamide reagents as an amide source, C-H amidation was realized at the ortho position of azine under the action of rhodium and boric acid. The method has mild reaction conditions, high atomic utilization, excellent yield, and wide adaptability to amidation reagents (both aromatic amides and fatty amides are applicable). Amide-substituted ketones can be obtained by a simple treatment and can be further transformed into bioactive substances. This provides a good supplement for the C-H bond amidation of aromatic rings.

C-H acylation of aniline derivatives with α-oxocarboxylic acids using ruthenium catalyst.

An efficient and convenient synthetic strategy for ruthenium(II)-catalyzed ortho-acylation of N-(2-pyridyl)-anilines using α-oxycarboxylic acids as acyl sources is described. The procedure can smoothly proceed under mild conditions, showing good functional group tolerance. Valuable ortho-acylated aniline products have been obtained with moderate to good yields. Furthermore, the reaction could be easily scaled up to the gram scale.

Rhodium-Catalyzed C(sp2)-H Amidation of Azine with Sulfonamides.

Direct C-H amidation of azine with sulfonamide was developed for the first time. The reactions proceeded smoothly under benign conditions and gave the corresponding products with high selectivity. This approach shows high regioselectivity, wide substrate scope, and functional group tolerance. Additionally, this transformation can also be scaled up to the gram level. This strategy allows for the direct preparation of ortho-sulfonamide-substituted ketone products, thus providing a good complement to previous C-H amidation.

Risk factors for postoperative stroke in adults patients with moyamoya disease: a systematic review with meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to clarify the risk factors for postoperative stroke in adult patients with moyamoya disease (MMD). METHODS: We comprehensively searched MEDLINE/PubMed, Web of Science, and Cochrane Library for eligible published literature with regard to the risk factors and postoperative complications in adult patients with MMD. Statistical analysis was conducted using Stata version 12.0. Pooled odds ratio (OR) with 95% confidence interval (CI) were assessed for each risk factor. RESULTS: There were 8 studies encompassing 1649 patients who underwent surgery with MMD were selected for analysis. Preoperative ischemic event significantly increase the risk of postoperative stroke events (OR = 1.40; 95%CI = 1.02-1.92; P = 0.039). PCA involvement correlate with an increased risk of post-infarction (OR = 4.60; 95%CI = 2.61-8.11; P = 0.000). Compared to direct bypass, patients who underwent indirect bypass or combined bypass could significantly increase the risk of postoperative stroke events. (OR = 1.17; 95%CI = 1.03-1.33; p = 0.017). MMD patients with diabetes were associated with an increased risk of postoperative stroke events (OR = 4.02, 95% CI = 1.59-10.16; p = 0.003). MMD patients with hypertension, age at onset and male sex were not associated with an increased risk of postoperative stroke events (P > 0.05). CONCLUSIONS: This systematic review and meta-analysis indicated that preoperative ischemic events, PCA involvement and diabetes were independent risk factors for postoperative stroke in MMD patients. Therefore, in order to ensure the curative effect of patients with MMD, it is very necessary to detect these risk factors and prevent postoperative complications in time.

[Application of relative quality constant in grades evaluation of bran stir-baked Aurantii Fructus].

The specifications of Chinese herbal medicines naturally form and exist in the circulation and use of Chinese herbal medicines.Buyers and sellers negotiate price by quality. With the increasing demand for public health care,the cultivation,processing methods and circulation of Chinese herbal medicines have changed. Under the mode of pursuing output and short-term benefits,the traditional grade evaluation method has been difficult to apply to the current quality status of the pieces. Bran stir-baked Aurantii Fructus is a genuine medicinal material in Jiangxi province. It is widely used,but the quality level of bran stir-baked Aurantii Fructus on the market is not uniform. Quality constant method was used in this paper for grading the Chinese herbal slices of bran stir-baked Aurantii Fructus. Sixteen batches of different quality samples were collected and tested,and finally,eleven qualified batches of them were chosen as researcher objects. The results showed that the relative quality constant ranged from 2. 52 to 5. 60. The relative quality constant was ≥4. 48 for first grade bran stir-baked Aurantii Fructus,2. 80-4. 48 for the second grade pieces,and <2. 80 for the third grade pieces. The grades evaluation method for bran stir-baked Aurantii Fructus established in this paper included both appearance and index composition. The results were objective,accurate,quantitative,applicable,and the method was simple to operate and easy to popularize. This study showed that the quality constant method could be applied to the grade evaluation of bran stir-baked Aurantii Fructus,providing a reference for the grade evaluation of fruit-type decoction pieces.

A facile three-step total synthesis of tanshinone I.

A facile synthetic approach for total synthesis of tanshinone I has been accomplished. The key precursor is a novel compound, epoxy phenanthraquinone. And this synthesis of tanshinone I is achieved in only three simple stages, which include Diels-Alder reaction, Δ(2)-Weitz-Scheffer-type epoxidation, and Feist-Bénary reaction from commercially available styrene.

Structural evolutions in polymer-derived carbon-rich amorphous silicon carbide.

The detailed structural evolutions in polycarbosilane-derived carbon-rich amorphous SiC were investigated semiquantitatively by combining experimental and analytical methods. It is revealed that the material is comprised of a Si-containing matrix phase and a free-carbon phase. The matrix phase is amorphous, comprised of SiC4 tetrahedra, SiCxOx-4 tetrahedra, and Si-C-C-Si/Si-C-H defects. With increasing pyrolysis temperature, the amorphous matrix becomes more ordered, accompanied by a transition from SiC2O2 to SiCO3. The transition was completed at 1250 °C, where the matrix phase started to crystallize by forming a small amount of ß-SiC. The free-carbon phase was comprised of carbon nanoclusters and C-dangling bonds. Increasing pyrolysis temperature led to the transition of the free carbon from amorphous carbon to nanocrystalline graphite. The size of the carbon clusters decreased first and then increased, while the C-dangling bond content decreased continuously. The growth of carbon clusters was attributed to Ostwald ripening and described using a two-dimensional grain growth model. The calculated activation energy suggested that the decrease in C-dangling bonds is directly related to the lateral growth of the carbon clusters.

Influence of Si and SiC Coating on the Microstructures and Mechanical Properties of C/C Bolts.

High-performance bolts made of carbon/carbon (C/C) composites are necessary for connecting thermally-insulating structural components of aerospace vehicles. To enhance the mechanical properties of the C/C bolt, a new silicon infiltration-modified C/C (C/C-SiC) bolt was developed via vapor silicon infiltration. The effects of silicon infiltration on microstructure and mechanical properties were systematically studied. Findings reveal that dense and uniform SiC-Si coating has been formed after silicon infiltration of the C/C bolt, strongly bonding with the C matrix. Under tensile stress, the C/C-SiC bolt undergoes a tensile failure of studs, while the C/C bolt is subject to the pull-out failure of threads. The breaking strength of the former (55.16 MPa) is 26.83% higher than the failure strength of the latter (43.49 MPa). Under double-sided shear stress, both the crushing of threads and the shear failure of studs occur within two bolts. As a result, the shear strength of the former (54.73 MPa) exceeds that of the latter (43.88 MPa) by 24.73%. According to CT and SEM analysis, matrix fracture, fiber debonding, and fiber bridging are the main failure modes. Therefore, a mixed coating formed by silicon infiltration can effectively transfer loads from coating to carbon matrix and carbon fiber, thereby enhancing the load-bearing capacity of C/C bolts.

Spatio-temporal distribution and overlap of Naemorhedus griseus and Capricornis milneedwardsii in Gongga Mountain, Sichuan, China.

Clarifying the distribution pattern and overlapping relationship of sympatric relative species in the spatio-temporal niche is important for our understanding of the behavioral relationship between species and the integrated management of multi-species habitats. Based on the infrared camera monitoring data from 2012 to 2021, we investigted the spatio-temporal distribution characteristics of the national secondary-class key protected animals Naemorhedus griseus and Capricornis milneedwardsii in the Gongga Mountain National Nature Reserve, Sichuan Province. We analyzed the distribution of N. griseuss and C. milneedwardsiis in the reserve using the MaxEnt model, based on 72 and 108 occurrence data of the two species, respectively, obtained by infrared cameras from 2016 to 2021, combined with 12 environmental factors potentially affecting their spatial distribution. Then, based on 1312 occurrence data of N. griseus and 1889 occurrence data of C. milneedwardsii collected by infrared camera from 2012 to 2021, we estimated their daily activity rhythms by using the kernel density estimation to understand the distribution pattern and overlap of the two species in the temporal niche. The results showed that the area of suitable habitats for N. griseus and C. milneedwardsii was 731.95 km2 and 1220.46 km2, respectively. The overlapping area was 697.17 km2. The main environmental factors had similar effects on the habitat selection of the two species. The daily activity of both species peaked in the early morning and evening. The utilization of the interval and intensity of the morning and evening time periods were different for the two species. The morning and evening activity peaks of C. milneedwardsii were earlier and later, respectively, than that of N. griseus. C. milneedwardsii had a higher utilization intensity during the nocturnal period. In general, high degree of spatial overlap and low degree of overlap in the temporal niche dimension contribute to the long-term coexistence of the two species.

Mammalian intermediate-term memory: new findings in neonate rat.

The ability of anisomycin, a translation inhibitor, and actinomycin, a transcription inhibitor to disrupt a cAMP/PKA-dependent odor preference memory in neonate rat was examined. Previous reports in invertebrates had described a novel translation-dependent intermediate-term memory dissected with these inhibitors, but similar effects have not been reported in mammalian memory systems. When anisomycin was infused into the olfactory bulb after the pairing of peppermint odor and the ß-adrenoceptor agonist isoproterenol (2mg/kg), short-term memory (1 or 3h) was intact, but intermediate (5h) and long-term (24h) memory was disrupted. When actinomycin was infused, only long-term memory was disrupted. This pattern of results is consistent with that reported in invertebrates for intermediate-term memory and led us to try a lower level of the unconditioned stimulus (isoproterenol) to isolate intermediate-term memory from long-term memory. Pups given a dose of 1.5mg/kg isoproterenol paired with peppermint odor showed memory for peppermint 5h, but not 24h, after training. These observations in the rat pup olfactory system parallel short-, intermediate- and long-term memory characteristics previously described in invertebrates. Odor preference memory in neonate rodents offers a tool to increase our understanding of the properties and mechanisms of multi-phasic memory in mammals.

Utility of CT Perfusion Imaging in Patients With Vertebral Artery Stenosis Treated With Balloon Expandable Stent.

Objective: To investigate the clinical value of CT perfusion (CTP) imaging in vertebral artery stenosis stenting, so as to provide the basis for preoperative and postoperative evaluation. Ninety-seven patients with vertebral artery stenosis were accepted for endovascular stenting between Jan 2016 and Jan 2020. CT angiography, Digital Subtraction Angiography, and CTP were performed pre-operation and post-operation. The cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transmit time (MTT) between the health and affected sides were analyzed statistically, and the imaging results pre- and post-operation were evaluated. The stenosis was relieved by endovascular stents in all 97 patients without serious complications. The abnormal perfusion was observed in 66 patients (68%). The differences in CBF and MTT between the diseased side and healthy side were statistically significant (P < 0.05). Compared with the preoperative imaging, the postoperative CTP was improved in 59 patients (89%). The differences in CBF and MTT between pre-operation and post-operation were statistically significant (P < 0.05). But there was no significant difference in CBV. CTP can sensitively reflect the perfusion of brain, and can also be used for preoperative and postoperative evaluation of vertebral artery stenting. It may be helpful as an adequate indicator of vertebral artery stenosis stent surgery.

The prognostic effects of hemodynamic parameters on rupture of intracranial aneurysm: A systematic review and meta-analysis.

BACKGROUND: Many risk factors are associated with rupture of intracranial aneurysm. However, the prognostic effects hemodynamic factors on intracranial aneurysm rupture remains poorly understood. A meta-analysis was performed based on contemporary studies to evaluate the prognostic effect of hemodynamic parameters on rupture of intracranial aneurysm. METHODS: The Cochrane Library, PubMed, Embase, and Web of Science were searched for cohort studies that analyzed hemodynamic parameters for intracranial aneurysm rupture prior to May 1, 2020. The standardized mean difference (SMD) and odds ratio (OR) with 95% confidence interval (CI) were calculated to assess the effect of individual hemodynamic parameters on intracranial aneurysm rupture. The primary outcomes were difference in wall shear stress (WSS), oscillatory shear index (OSI) and low shear index (LSA) between ruptured and unruptured intracranial aneurysm. Two reviewers independently assessed the quality of the trials and the associated data. All statistical analyses were performed using standard statistical procedures in Review Manager 5.2. RESULTS: A total of 15 studies including 779 patients with 900 aneurysms were identified for this meta-analysis. The pooled results indicated that the average WSS, OSI and LSA% had significant associations with rupture of intracranial aneurysm, with pooled SMDs of -0.36 (95% CI -0.57 to -0.15; P = 0.001), 0.37 (95% CI 0.19 to 0.55; P < 0.0001) and 0.57% (95% CI 0.18 to 0.95; P = 0.004), respectively. In addition, other hemodynamic parameters, including aneurysm size, aspect ratio, mean volume, undulation index, ellipticity index, nonsphericity index, number of vorticies, and relative residence time significant associations with intracranial aneurysm rupture. Multivariate analysis indicated that circumferential wall tension, angle btwn, irregular shape and size of aneurysms were independent risk factors of intracranial aneurysm rupture. CONCLUSIONS: This meta-analysis identified WSS, OSI and LSA% as influential hemodynamic parameters on rupture of intracranial aneurysm. The roles of other hemodynamic parameters and risk factors for intracranial aneurysm rupture need further assessments in future.

Selective extraction and column separation for 16 kinds of rare earth element ions by using N, N-dioctyl diglycolacid grafted silica gel particles as the stationary phase.

The selective extraction and column separation rear earth elements (REEs) were investigated in the present work. Herein, the functional ligand of N, N-dioctyldiglycolic acid (DODGA) was synthesized and chemically grafted on the silica gel (SG) particles to give the novel material SG@DODGA. The obtained SG@DODGA was fully characterized by NMR, BET (Brunauer-Emmett-Teller) N2 physisorption analysis, atom force microscopy (AFM), scanning electronic microscopy (SEM), Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA). After investigating the adsorption capability of the SG@DODGA towards 16 kinds of REEs (La, Ce, Pr, Nd, Sm, Eu, Gd, Td, Dy, Ho, Er, Tm, Yb, Lu, Y and Sc), the results showed that the adsorption kinetic data was better fitted with pseudo-second-order model and Elovich model, the adsorption isotherms data was suitable for Freundlich model. The above result also indicated that the adsorption mechanism between the SG@DODGA and REEs was chemical ion exchange. Moreover, choose SG@DODGA as the column chromatography stationary phase and packed in a glass column for the column studies to obtain breakthroughs profile of each REEs. Furthermore, the column was used to try to separate the mixed 16 kinds of REEs. The first attempt to preliminary separate REEs result showed that this column could be applied for simply separating REEs. The light REEs La, Ce, Pr, Nd exhibited better separation effect than the other REEs.

Why are HIV-1 fusion inhibitors not effective against SARS-CoV? Biophysical evaluation of molecular interactions.

The envelope spike (S) glycoprotein of the severe acute respiratory syndrome associated coronavirus (SARS-CoV) mediates the entry of the virus into target cells. Recent studies point out to a cell entry mechanism of this virus similar to other enveloped viruses, such as HIV-1. As it happens with other viruses peptidic fusion inhibitors, SARS-CoV S protein HR2-derived peptides are potential therapeutic drugs against the virus. It is believed that HR2 peptides block the six-helix bundle formation, a key structure in the viral fusion, by interacting with the HR1 region. It is a matter of discussion if the HIV-1 gp41 HR2-derived peptide T20 (enfuvirtide) could be a possible SARS-CoV inhibitor given the similarities between the two viruses. We tested the possibility of interaction between both T20 (HIV-1 gp41 HR2-derived peptide) and T-1249 with S protein HR1- and HR2-derived peptides. Our biophysical data show a significant interaction between a SARS-CoV HR1-derived peptide and T20. However, the interaction is only moderate (K(B)=(1.1+/-0.3)x10(5) M(-1)). This finding shows that the reasoning behind the hypothesis that T20, already approved for clinical application in AIDS treatment, could inhibit the fusion of SARS-CoV with target cells is correct but the effect may not be strong enough for application.

Reversal of P-gp and BCRP-mediated MDR by tariquidar derivatives.

With an aim to generate non-toxic, specific and highly potent multidrug resistance (MDR) modulators, a novel series of anthranilic acid amide-substituted tariquidar derivatives were synthesized. The new compounds were evaluated for their cytotoxicity toward normal human colon fibroblasts (CCD18-Co), human gastric epithelial cell line (HFE) and primary rat liver cells, and for their ability to inhibit P-gp/BCRP-mediated drug efflux and reversal of P-gp and BCRP-mediated MDR in parental and drug-resistant cancer cell lines (LCC6 MDR1, MCF-7 FLV1000, R-HepG2, SW620-Ad300). While tariquidar is highly toxic to normal cells, the new derivatives exhibited much lower or negligible cytotoxicity. Some of the new tariquidar derivatives inhibited both P-gp and BCRP-mediated drug efflux whereas a few of them bearing a sulfonamide functional group (1, 5, and 16) are specific to P-gp. The new compounds were also found to potentiate the anticancer activity of the transporter substrate anticancer drugs in the corresponding transporter-overexpressing cell lines. The extent of resistance reversal was found to be consistent with the transporter inhibitory effect of the new derivatives. To further understand the mechanism of P-gp and BCRP inhibition, the tariquidar derivatives were found to interact with the transporters using an antibody-based UIC2 or 5D3 shift assay. Moreover, the transporters-inhibiting derivatives were found to modulate the ATPase activities of the two MDR transporters. Our data thus advocate further development of the new compounds for the circumvention of MDR.

Evaluation and SAR analysis of the cytotoxicity of tanshinones in colon cancer cells.

AIM: This study was designed to evaluate the anti-cancer actions of tanshinone I and tanshinone IIA, and six derivatives of tanshinone IIA on normal and cancerous colon cells. Structure activity relationship (SAR) analysis was conducted to delineate the significance of the structural modifications of tanshinones for improved anti-cancer action. METHOD: Tanshinone derivatives were designed and synthesized according to the literature. The cytotoxicity of different compounds on colon cancer cells was determined by the MTT assay. Apoptotic activity of the tanshinones was measured by flow cytometry (FCM). RESULTS: Tanshinone I and tanshinone IIA both exhibited significant cytotoxicity on colon cancer cells. They are more effective in p53(+/+) colon cancer cell line. It was also noted that the anti-cancer activity of tanshinone I was more potent and selective. Two of the derivatives of tanshinone IIA (N1 and N2) also exhibited cytotoxicity on colon cancer cells. CONCLUSION: The anti-colon cancer activity of tanshinone I was more potent and selective than tanshinone IIA, and is p53 dependent. The derivatives obtained by structural modifications of tanshinone IIA exhibited lower cytotoxicity on both normal and colon cancer cells. From steric and electronic characteristics point of view, it was concluded that structural modifications of ring A and furan or dihydrofuran ring D on the basic structure of tanshinones influences the activity. An increase of the delocalization of the A and B rings could enhance the cytotoxicity of such compounds, while a non-planar and small sized D ring region would provide improved anti-cancer activity.

Chemical conjugation of muramyl dipeptide and paclitaxel to explore the combination of immunotherapy and chemotherapy for cancer.

Paclitaxel (Taxol) conjugated to muramyl dipeptide (MDP) is described. Biological testing showed that the conjugation of MDP at 2'-O-paclitaxel (2'- O -MTC-01) not only has antitumor activity, but also have immunoenhancement capacity. Compared with paclitaxel or MDP alone or with a mixture of paclitaxel + MDP, 2'- O -MTC-01 significantly increases the production and expression of TNF-alpha and IL-12 from mouse peritoneal macrophages, which demonstrates a synergism of MDP and paclitaxel in one conjugated molecule.

Eremophilenolides and other constituents from the roots of Ligularia sagitta.

Chemical investigation of the roots of Ligularia sagitta has resulted in the characterization of six eremophilenolides 6beta,8beta-dimethoxy-10beta-hydroxyeremophil-7(11)-en-12,8alpha-olide (1), 6beta-angeloyloxy-10beta-hydroxy-8beta-methoxyeremophil-7(11)-en-12,8alpha-olide (2), 6beta-(2'-methylbutanoyloxy)-10beta-hydroxy-8beta-methoxyeremophil-7(11)-en-12,8alpha-olide (3), 6beta-angeloyloxy-10beta-hydroxy-8alpha-methoxyeremophil-7(11)-en-12,8beta-olide (4), 6beta-(2'-methylbutanoyloxy)-10beta-hydroxy-8alpha-methoxyeremophil-7(11)-en-12,8beta-olide (5) and 8beta,10beta-dihydroxy-6beta-methoxyeremophil-7(11)-en-12,8alpha-olide (6), together with one monoterpene (3 R,4 R,6 S)-3,6-dihydroxy-1-menthene (7), two triterpenes lupeol (8) and ursolic acid (9), and beta-sitosterol (10). The structures of five new constituents (1-5) were elucidated by spectroscopic methods including 2D-NMR experiments. The compounds 1, 5 and 7 showed antibacterial activity by being assayed against Staphylococcus aureus, Bacillus subtilis and Escherichia coli.