Copper Difluorocarbene Enables Catalytic Difluoromethylation.

Despite the synthetic versatility of difluorocarbene, its high reactivity severely regulates widespread applications of difluorocarbene in organic synthesis. Here, we report a copper difluorocarbene-involved catalytic coupling, representing a new mode of the difluoromethylation reaction. This method allows difluoromethylation of a wide range of readily available allyl/propargyl electrophiles with NaBH3CN and low-cost difluorocarbene precursor BrCF2CO2K, featuring high cost-efficiency, high stereo- and regioselectivities, and high functional group tolerance, even with complex drug-like molecules. Applying the method led to the efficient synthesis of deuterated difluoromethylated compounds of medicinal interest. The resulting difluoromethylated allyl and allenyl products can serve as versatile synthons for diverse transformations, rendering the approach attractive for synthesizing complex fluorinated structures. Experimental mechanistic studies and computational calculations reveal that the formation of a difluoromethylcopper(I) intermediate through the nucleophilic attack of boron hydride on the copper(I) difluorocarbene is the key step in the reaction.

Late-stage gem-difluoroallylation of phenol in bioactive molecules and peptides with 3,3-difluoroallyl sulfonium salts.

An efficient method for the late-stage selective O-fluoroalkylation of tyrosine residues with a stable yet highly reactive fluoroalkylating reagent, 3,3-difluoroallyl sulfonium salts (DFASs), has been developed. The reaction proceeds in a mild basic aqueous buffer (pH = 11.6) with high efficiency, high biocompatibility, and excellent regio- and chemoselectivity. Various oligopeptides and phenol-containing bioactive molecules, including carbohydrates and nucleosides, could be selectively O-fluoroalkylated. The added vinyl and other functional groups from DFASs can be valuable linkers for successive modification, significantly expanding the chemical space for further bioconjugation. The synthetic utility of this protocol has been demonstrated by the fluorescently labeled anti-cancer drug and the synthesis of O-link type 1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid-tyrosine3-octreotate (DOTA-TATE), showing the prospect of the method in medicinal chemistry and chemical biology.

Current situation and trend of translational research of acupuncture-moxibustion in treatment of aphasia based on knowledge graph analysis. / åŸºäºŽçŸ¥è¯†å›¾è°±æŠ€æœ¯åˆ†æžé’ˆç¸æ²»ç–—å¤±è¯­ç—‡è½¬åŒ–ç ”ç©¶çš„çŽ°çŠ¶ä¸Žè¶‹åŠ¿.

OBJECTIVES: To investigate the hot topics in acupuncture-moxibustion research for treatment of aphasia and explore the current situation and trend of technology transformation in this field through analyzing the relevant Chinese literatures in recent 30 years by means of knowledge graph technology. METHODS: CiteSpace 6.1.R 2 and VOSviewer V1.6.16 software were used to collate the data, draw knowledge graphs and conduct visual analysis of the literatures related to acupuncture-moxibustion treatment of aphasia, searched from CNKI, WanFang and VIP databases.The time line view and strongest bursts of keywords were formed in the field of acupuncture-moxibustion treatment for aphasia. The treatment-based keyword networks were visualized. RESULTS: A total of 773 Chinese articles were included. Through visual analysis of the co-occurrence networks, the top 10 high-frequency overall keywords and the top 10 clusters of overall keywords were listed. The top 5 high-frequency aphasia categories were Broca aphasia, hysterical aphasia, transcortical motor aphasia, nominal aphasia and sensory aphasia. Regarding the keywords of the techniques of acupuncture-moxibustion, the occurrence frequencies of scalp acupuncture, tongue acupuncture, body acupuncture and electroacupuncture were ≥ 10 times.The occurrence frequencies of 16 acupoints were ≥25 times. After collation and cluster analysis of acupoints and techniques of acupuncture-moxibustion, 7 keyword clusters of "acupuncture techniques-acupoints" were obtained. The time line view showed that the strongest burst of keywords were transcranial magnatic stimulation, language rehabilitation training, acupuncture-medicine therapy and stroke, etc. in the recent 5 years. CONCLUSIONS: Acupuncture-moxibustion displays its unique advantage in treatment of aphasia. With the deepening of modern research, the hot topics for aphasia treated with acupuncture-moxibustion are present and the achievements enriched. In future, these therapeutic methods should be further investigated to explore a model of translational medicine for aphasia in line with the characteristics of acupuncture-moxibustion.

Fabrication and Study of Dextran/Sulfonated Polysulfone Blend Membranes for Low-Density Lipoprotein Adsorption.

The abnormal increase in low-density lipoprotein (LDL) in human blood is a main independent risk factor for the pathogenesis of atherosclerosis, whereas a reduced LDL level effectively lowers morbidity. It is important to develop LDL adsorption materials with high efficiency and selectivity, as well as to simplify their fabrication processes. In this paper, polysulfone (PSF), sulfonated polysulfone (SPSF), and sulfonated polysulfone/dextran (SPSF/GLU) membranes were successfully fabricated for LDL adsorption using a solution casting technique. Attenuated total reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy measurements confirmed the success of the preparation. The water contact angle decreased from 89.7 ± 3.4° (PSF) to 76.4 ± 3.2° (SPSF) and to 71.2 ± 1.9° (SPSF/GLU), respectively. BSA adsorption testing showed that the SPSF/GLU with surface enrichment of sulfonate groups and glycosyl groups possessed higher resistance to protein solution. The adsorption and desorption behaviors of the studied samples in single-protein or binary-protein solutions were systematically investigated by enzyme-linked immunosorbent assay (ELISA), The results showed that SPSF/GLU, which had excellent resistance to protein adsorption, possessed a similar adsorption capacity to that of PSF. SPSF membrane exhibited excellent selective affinity for LDL in single and binary protein solutions, suggesting potential applications in LDL removal.

(E)-2-styrylanthracene-9,10-dione derivatives as novel fluorescent probes: synthesis, photophysical properties and application in mitochondria imaging.

Our previous work firstly reported that (E)-2-styrylanthracene-9,10-dione is a novel fluorescent core (EK01) with the ability of specific mitochondria imaging. In this effort, we mainly focused our attention on the structure-photophysical property relationship and application in cells imaging of this new fluorescent chemotype. A series of the structural derivatives (TZ series) were designed and synthesized by introducing some substituents onto the 2-styryl moiety. The structure-photophysical property relationship analysis suggested that TZ03 is an excellent fluorescent molecular building block with the property of fluorescent "turn-on" effect after the modification of acylation, and TZ07 is an excellent fluorescent dye with a series of advantages such as high fluorescence intensity (Fmax = 4049.0 in CH2Cl2, 25.80 µM), moderate molar extinction coefficients (3.77 × 103-5.93 × 103 mol-1∙L∙cm-1), strong fluorescence quantum yield (Φmax = 0.739 in CH2Cl2), large Stokes shift (99.0 nm-161.8 nm) and well biological tolerance. As a classical D-π-A structure, the ICT characteristic of TZ07 was analyzed through spectroscopy verification and DFT calculations. Furthermore, optimized compound TZ07 was successfully applied in the living cells imaging with the excellent selectivity to mitochondria in a green fluorescent form. It was also suggested that the mechanism of TZ07 targeting mitochondria is independent of mitochondrial membrane potential, but probably related to the mitochondrial complex I. These findings may provide some insights into the development of novel mitochondria-targeted fluorescent probes.

[Accumulation and Transport Characteristics of Cd, Pb, Zn, and As in Different Maize Varieties].

The enrichment and translocation characteristics of Cd, Pb, Zn, and As by various parts of maize plants were investigated using field experiments in 22 maize varieties simultaneously under uncontaminated, low, middle, and serious heavy metal Cd, Pb, Zn, and As complex-contaminated farmland soil conditions. The relationship between the uptake of Cd, Pb, Zn, and As by maize plants and the morphological content of heavy metals in the soil was also discussed through principal component analysis and correlation analysis of the concentrations of eight heavy metals, including Cd, Hg, As, Pb, Cr, Cu, Ni, and Zn. The results showed that:① the distribution pattern of Cd and Zn contents in different parts of the maize plant was as follows:upper stalk>lower stalk>root>seed, the distribution pattern of Pb was As follows:root>lower stalk>upper stalk>seed, and the As distribution pattern was:root>upper stalk>lower stalk>seed. The different distribution patterns were closely related to the accumulation characteristics of the crop itself and the environmental activity of Cd, Pb, Zn, and As in the soil of the study area. ② There were significant differences in Cd and Pb accumulation among 22 maize cultivars due to their genetic background (P<0.05), which showed four trends:Cd and Pb compound high-accumulation varieties, single Cd or Pb low-accumulation varieties (low Cd and high Pb, low Pb and high Cd), and Cd and Pb compound low-accumulation varieties. Among them, the content of Cd in the grain of the three varieties exceeded the national food safety standard, and the content of Cd in the stem and leaf of 14 varieties exceeded the national food health standard. The Pb content in stems, leaves, and grains of all cultivars did not exceed the standard, but the Pb content in grains of some cultivars was close to the limit and had the risk of exceeding the standard. The content of As in the stem, leaf, and grain of different maize varieties was much lower than the standard limit value, showing a stable low-accumulation characteristic. The content of Zn in the stem and leaf of different maize varieties increased with the increase in the content of Zn in soil, but the content of Zn in grain remained within the threshold of normal plant growth. ③ Cd, Pb, Zn, and As in maize plants in the study area had a certain homology and were mainly affected by the excessive levels of Cd, Pb, Zn, and As pollutants in the soil. This showed that anthropogenic sources were brought about by mine extraction and tailings stockpiles, whereas Cu elements in maize plants were affected by certain anthropogenic pollution sources, though to a limited extent. Hg, Ni, and Cr in maize plants had a certain homology; this showed the natural source of soil parent material and weathering product accumulation. ④ The contents of Cd, Pb, Zn, and As elements in various parts of the corn plant, as well as the contents of Cr and Ni elements all had a very significant positive correlation (P<0.01). The transport mechanisms of Cd, Pb, Zn, and As elements in the plant may have a common. However, there was a synergistic effect in the migration from the root of the corn to the upper part of the ground, and the same was true for the elements of Cr and Ni. The elements of Hg and Cd, Pb, Zn, and As in the corn stems and leaves and Hg and Cd, Hg, As, Pb, Cr, Ni, and Zn in grains all showed certain antagonistic effects. ⑤ The comparison method simultaneously satisfied the following requirements:the contents of Cd, Pb, and As in stems and leaves did not exceed the national food hygiene standards, and the contents of Cd, Pb, and As in the grains did not exceed the national food safety standards. The cluster analysis of Cd, Pb, and As in grains was a low-accumulation group, and the enrichment and transport coefficients of Cd, Pb, and As in the stems and leaves and grains were low as the optimal conditions. C18 (Xianyu 335) could be selected as the optimal maize variety with low accumulation of Cd, Pb, and As and normal Zn content in grain, which is suitable for promoting and applying in the heavy metal complex-polluted farmland around industrial and mining enterprises in north China.

Palladium-Catalyzed Carbonylative Cross-Coupling of Difluoroalkyl Halides with Alkylboranes under 1 atm of CO.

A palladium catalyzed carbonylative cross-coupling of difluoroalkyl halides with alkyl-9-BBN under 1 atm of CO has been developed. The reaction shows broad substrate scope and high functional group tolerance, even toward complex pharmaceuticals, providing a general and straightforward method to access alkyldifluoroalkyl ketones. Preliminary mechanistic studies reveal that a radical pathway is involved in the reaction.

Pheochromocytoma with abdominal aortic aneurysm presenting as recurrent dyspnea, hemoptysis, and hypotension: A case report.

BACKGROUND: Pheochromocytomas are rare endocrine tumors with various clinical manifestations, and few of them might present with profound, life-threatening conditions. CASE SUMMARY: We report the case of a 65-year-old man who complained of sudden dyspnea and hemoptysis for half a day. There was no obvious cause for the patient to have dyspnea, coughing, or coughing up to approximately 100 mL of fresh blood. Finally, he was diagnosed with pheochromocytoma crisis (PCC), coexisting with an abdominal aortic aneurysm (AAA). CONCLUSION: We report a case of pheochromocytoma presenting with recurrent hemoptysis, dyspnea and hypotension coexisting with an AAA. It not only proved the uncommon manifestations of pheochromocytoma but also directed clinicians to consider PCC among the possible diagnoses when meeting similar cases. Moreover, surgical excision is the most beneficial method for the treatment of pheochromocytoma coexisting with AAA when the situation is stable.

Nickel-Catalyzed Four-Component Carbocarbonylation of Alkenes under 1 atm of CO.

Transition-metal-catalyzed carbonylation is one of the most straightforward strategies to prepare carbonyl compounds. However, compared to well-established noble-metal-catalyzed carbonylation reactions, analogue coupling via base-metal, nickel catalysis has received less attention because of the easy formation of highly toxic and unreactive Ni(CO)4 species between Ni(0) and CO. To date, the use of inexpensive and widely available carbon monoxide (CO) gas for nickel-catalyzed carbonylation reaction remains challenging, and nickel-catalyzed four-component carbonylative reaction has not been reported yet. Here, we report a highly selective nickel-catalyzed four-component carbocarbonylation of alkenes under 1 atm (1 atm) of CO gas to efficiently achieve an array of complex carbonyl compounds, including fluorinated amino acids and oligopeptides of great interest in medicinal chemistry and chemical biology. This reaction relies on a nickel-catalyzed one-pot cascade process to assemble CO, arylboronic acids, and difluoroalkyl electrophiles across the carbon-carbon double bond of alkenes, paving a new way for base-metal-catalyzed carbonylative cascade reaction.

[Delayed combined approach with three plates internal fixation for Pilon fracture with fibula fracture].

OBJECTIVE: To explore clinical effect of delayed internal fixation through anteromedial and posterolateral approach of ankle joint in treating Pilon fracture combined with fibula fracture. METHODS: From December 2016 to December 2018, 18 patients with Pilon and fibula fracture treated by internal fixation through anteromedial and posterolateral approach of ankle joint with three plates, including 12 males and 6 females, aged from 38 to 51 years old with an average of (44.00±3.45) years old. According to classification of Rüedi and Allgöwer, 9 patients were typeⅡand 9 patients were type Ⅲ. All patients were closed fractures. Burnell Charnley standard was used to evaluate reduction of articular surface fracture at 7 days after operation, and Mazur ankle evaluation grading system was used to compare the improvement of ankle function between 9 and 12 months after operation. RESULTS: All patients were followed up for 12 to 18 months with an average of (14.00± 1.57) months. According to standard of Burwell Charnley at 7 days after operation, 13 patients got excellent results and 5 patients good. All fracture healed well from 9.5 to 15 months with an average of (12.00±1.43) months. No infection, skin necrosis, loosen and broken of internal fixation, loosing of fracture reduction occurred. Mazur ankle joint score at 12 months (92.11± 5.28) scores was higher than 9 months (89.33±5.20) scores (t=7.976, P<0.001) . CONCLUSION: Delayed internal fixation through anteromedial and posterolateral approach of ankle joint for Pilon fracture combined with fibula fracture has advantages of simple operation, satisfied reduction, stable fixation, less postoperative complications and satisfied ankle joint function.

Nickel-Catalyzed Carbonylation of Difluoroalkyl Bromides with Arylboronic Acids.

A nickel-catalyzed carbonylative difluoroalkylation reaction with arylboronic acids under 1 atm of CO has been developed. The reaction proceeds under mild reaction conditions with high efficiency and high functional group tolerance. Preliminary mechanistic studies reveal that the arylacyl nickel complex is the key intermediate to circumvent the formation of labile fluoroacyl nickel, and bimetallic oxidative addition is likely the key step to facilitate the catalytic cycle.

Highly Selective Pd-Catalyzed Direct C-F Bond Arylation of Polyfluoroarenes.

A directing-group-free palladium-catalyzed direct arylation of simple polyfluoroarenes with arylboronic acids through selective C-F bond activation is described. The combination of Pd(OAc)2 with BrettPhos was identified as an efficient catalytic system to promote the reaction with high regioselectivity and broad substrate scope. Preliminary mechanistic studies reveal that the oxidative addition of Pd to the C-F bond is involved in the catalytic cycle.

Rapamycin-ameliorated diabetic symptoms involved in increasing adiponectin expression in diabetic mice on a high-fat diet.

Recent studies showed that rapamycin improved diabetic complications. Here, we investigated the metabolic effects of rapamycin in type 2 diabetes model (T2DM) mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2 mg/kg or vehicle only for 3 weeks and were maintained on a high-fat diet. The treated diabetic mice exhibited decreased body weight, blood glucose levels, and fat mass. FGF21 expression was suppressed in C57B/L6 mice, but adiponectin expression increased both in FGF21 KO and C57B/L6 mice. These results suggest that rapamycin may alleviate FGF21 resistance in mice on a high-fat diet. The reduction of adipose tissue mass of the diabetic mice may be due to the increased adiponectin.

High flux MWCNTs-interlinked GO hybrid membranes survived in cross-flow filtration for the treatment of strontium-containing wastewater.

Graphene oxide (GO)-based membranes provide an encouraging opportunity to support high separation efficiency for wastewater treatment. However, due to the relatively weak interaction between GO nanosheets, it is difficult for bare GO-based membranes to survive in cross-flow filtration. In addition, the permeation flux of the bare GO membrane is not high sufficiently due to its narrow interlayer spacing. In this study, GO membranes interlinked with multi-walled carbon nanotubes (MWCNTs) via covalent bonds were fabricated on modified polyacrylonitrile (PAN) supports by vacuum filtration. Due to the strong bonds between GO, MWCNTs and the PAN membrane, the membranes could be used for the treatment of simulated nuclear wastewater containing strontium via a cross-flow process. The result showed a high flux of 210.7L/(m2h) at 0.4MPa, which was approximately 4 times higher than that of commercial nanofiltration membranes. The improved water permeation was attributed to the nanochannels created by the interlinked MWCNTs in the GO layers. In addition, the hybrid membrane exhibited a high rejection of 93.4% for EDTA-chelated Sr2+ in an alkaline solution, and could also be used to separate Na+/Sr2+ mixtures. These results indicate that the MWCNTs-interlinked GO membrane has promising prospects for application in radioactive waste treatment.

Carbonylation of Difluoroalkyl Bromides Catalyzed by Palladium.

Although important progress has been made in the fluoroalkylation reactions, the transition-metal-catalyzed carbonylative fluoroalkylation reaction remains challenging so far. Herein, we report the first example of a Pd-catalyzed carbonylation of difluoroalkyl bromides with (hetero)arylboronic acids under one atmosphere pressure of CO. The reaction can also be extended to the aryl potassium trifluoroborate salts. The advantages of this protocol are synthetic simplicity, broad substrate scope, and excellent functional group compatibility. The resulting difluoroalkyl ketones can serve as versatile building blocks for the synthesis of various useful fluorinated compounds.

Research Advances in Tissue Engineering Materials for Sustained Release of Growth Factors.

Growth factors are a class of cytokines that stimulate cell growth and are widely used in clinical practice, such as wound healing, revascularization, bone repair, and nervous system disease. However, free growth factors have a short half-life and are instable in vivo. Therefore, the search of excellent carriers to enhance sustained release of growth factors in vivo has become an area of intense research interest. The development of controlled-release systems that protect the recombinant growth factors from enzymatic degradation and provide sustained delivery at the injury site during healing should enhance the growth factor's application in tissue regeneration. Thus, this study reviews current research on commonly used carriers for sustained release of growth factors and their sustained release effects for preservation of their bioactivity and their accomplishment in tissue engineering approaches.

A general synthesis of fluoroalkylated alkenes by palladium-catalyzed Heck-type reaction of fluoroalkyl bromides.

An efficient palladium-catalyzed Heck-type reaction of fluoroalkyl halides, including perfluoroalkyl bromides, trifluoromethyl iodides, and difluoroalkyl bromides, has been developed. The reaction proceeds under mild reaction conditions with high efficiency and broad substrate scope, and provides a general and straightforward access to fluoroalkylated alkenes which are of interest in life and material sciences.

Special plant species determines diet breadth of phytophagous insects: a study on host plant expansion of the host-specialized Aphis gossypii Glover.

Host specialization is a ubiquitous character of phytophagous insects. The polyphagous population is usually composed of some subpopulations that can use only a few closely related plants. Cotton-melon aphids, Aphis gossypii Glover exhibited strong host specialization, and the cotton- and cucurbits-specialized biotypes had been clearly identified. However, the experimental work that addressed the roles of plant species in determining diet breadth of phytophagous insects is rare. In the present study, we took the artificial host transfer method to assess the role of two special plants, zucchini Cucurbita zucchini L. and cowpea Vigna unguiculata (Linn.) Walp, in regulating diet breadth of cotton- and cucurbits-specialized A. gossypii collected from cotton and cucumber fields and reared separately on the native host plant for ten years. The results showed that the cotton-specialized aphids did not directly use cucumber whereas the cucurbits-specialized did not use cotton regardless of the coexistence or separation of cotton and cucumber plants. Neither of the cotton- and cucurbits-specialized aphids could use capsicum Capsicum annuum, eggplant Solanum melongenahttp://en.wikipedia.org/wiki/Carolus_Linnaeus, tomato Solanum lycopersicum, maize Zea mayshttp://en.wikipedia.org/wiki/Carl_Linnaeus, and radish Raphanus sativus, however, both of them could use zucchini and cowpea. Moreover, the feeding experience on zucchini led the cotton-specialized aphids to use cucumber well and finally to be transformed into the cucurbits-specialized biotype. The short-term feeding experience on cowpea resulted in the diet breadth expansion of the cucurbits-specialized aphids to use cotton. On the other hand, the diet breadth expansion of the cucurbits- and cotton-specialized aphids was only realized by different species of plant. It concluded that the special host plant did induce the conversion of feeding habits in the cotton- and cucurbits-specialized aphids, and consequently broke the host specialization. The plant species is an underlying factor to determine the diet breadth of phytophagous insects.

[Simple Pemberton's ilium osteotomy and combined unter-trochanter derotation-varisation osteotomy for developmental dysplasia of the hip].

OBJECTIVE: To retrospectively compare the therapeutic effects of simple Pemberton's ilium osteotomy and combined unter-trochanter derotation-varisation osteotomy for developmental dysplasia of the hip (DDH). METHODS: Clinical data of 141 DDH patients who received either simple Pemberton's ilium osteotomy (n=57; 12 male and 45 female; age range 3-8 years) or combined unter-trochanter derotation-varisation osteotomy (n=84; 15 male and 69 female; age range 4-9 years) from January 2004 to January 2009 were collected. Postoperative complications, Severin's radiological outcomes and therapeutic outcomes as evaluated by Mcay criteria were compared between the two groups 2 years after operation. RESULTS: The patients in simple Pemberton group were followed-up for 30-52 months (mean 38 months) and the patients in the combination group were followed-up for 32-51 months (mean 37 months). There were 7 cases of dislocation, 4 cases of avescular necrosis of femoral head and 5 cases of joint stiffness in simple Pemberton group vs 0 case of dislocation, contraction of the limb and ANFH,2 cases of joint stiffness in the combination group. Two years after surgery, the result as evaluated by McKay criteria was excellent in 27 cases, good in 18 cases and fair in 12 cases in simple Pemberton group vs. 52, 25 and 7 cases in the combination group. The overall clinical outcome in the combination group was better than that in simple Pemberton group. Severin X-ray evaluation showed excellent in 27 cases, good in 15 cases and fair in 15 cases in simple Pemberton group vs. 53, 22 and 9 cases in the combination group,indicating that the overall result in the combination group was better than that in simple Pemberton group. CONCLUSION: The overall clinical outcome of the combination group is better than that of simple Pemberton group in the treatment of pediatric DDH, especially in reducing postoperative complications and functional recovery. The patients in the combination group reported a higher postoperative satisfaction as compared with those in simple Pemberton group.

[Application of wavelet transform for ECG signal denoising].

Based on the wavelet transform, the ways and process of wavelet de-noising are presented in the paper. The detail experimental results show that wavelet de-noising is better than traditional filtering ways, and the soft-threshold denoising is obviously better than the hard- threshold denoising.