Sodium Carbonate-Promoted Formation of 5-Amino-1,2,4-thiadiazoles and 5-Amino-1,2,4-selenadiazoles with Elemental Sulfur and Selenium.

Sodium carbonate-promoted facile synthesis of 5-amino-1,2,4-thiadiazoles and 5-amino-1,2,4-selenadiazoles with elemental sulfur and selenium, respectively, was developed. This method was carried out with O2 in the air as the green oxidant, and it has several advantages, including low cost, low toxicity, and stable sulfur and selenium sources, good to excellent yields with water as the sole byproduct, simple operation, and a broad substrate scope. Preliminary mechanistic studies indicate that the formation of the 1,2,4-thiadiazole ring and the 1,2,4-selenadiazole ring undergoes different processes.

Structure and activity of SLAC1 channels for stomatal signaling in leaves.

Stomata in leaves regulate gas exchange between the plant and its atmosphere. Various environmental stimuli elicit abscisic acid (ABA); ABA leads to phosphoactivation of slow anion channel 1 (SLAC1); SLAC1 activity reduces turgor pressure in aperture-defining guard cells; and stomatal closure ensues. We used electrophysiology for functional characterizations of Arabidopsis thaliana SLAC1 (AtSLAC1) and cryoelectron microscopy (cryo-EM) for structural analysis of Brachypodium distachyon SLAC1 (BdSLAC1), at 2.97-Å resolution. We identified 14 phosphorylation sites in AtSLAC1 and showed nearly 330-fold channel-activity enhancement with 4 to 6 of these phosphorylated. Seven SLAC1-conserved arginines are poised in BdSLAC1 for regulatory interaction with the N-terminal extension. This BdSLAC1 structure has its pores closed, in a basal state, spring loaded by phenylalanyl residues in high-energy conformations. SLAC1 phosphorylation fine-tunes an equilibrium between basal and activated SLAC1 trimers, thereby controlling the degree of stomatal opening.

Three-Component Domino Reaction of Thioamide, Isonitriles, and Water: Selective Synthesis of 1,2,4-Thiadiazolidin-3-ones and (E)-N-(1,2-Diamino-2-thioxoethylidene)benzamides.

The three-component domino reaction of thioamides, benzyl isocyanide, and water in the presence of a catalytic amount of both Pd(dppf)Cl2 and Cu(OAc)2 afforded novel 1,2,4-thiadiazolidin-3-one cyclic compounds, whereas the same reaction with tertiary alkylisonitriles in the presence of rare earth metal salt [La(OTf)3] resulted in (E)-N-(1,2-diamino-2-thioxoethylidene)benzamide open-chain products. This divergent reaction enabled the one-pot construction of five (N-S, C-S, C-O, and two C-N) or four (C-S, C-N, C-O, and C-C) new chemical bonds. Mechanism studies indicate that the oxygen atom of the product was derived from H2O.

Electrocatalytic ring-opening dihydroalkoxylation of N-aryl maleimides with alcohols under metal- and oxidant-free conditions.

The electrocatalytic ring-opening dihydroalkoxylation of N-aryl maleimides with alcohols under metal- and oxidant-free conditions is described. This electrochemical process consists of anodic single-electron transfer oxidation, cathodic radical reduction, rearrangement-ring cleavage and nucleophilic addition cascade, which employs tetrabutylammonium bromide not only as a redox catalyst but also as an efficient supporting electrolyte, and offers a practical and environmentally friendly route to ring-opening difunctionalization products.

Scaling-up and proteomic analysis reveals photosynthetic and metabolic insights toward prolonged H2 photoproduction in Chlamydomonas hpm91 mutant lacking proton gradient regulation 5 (PGR5).

Clean and sustainable H2 production is crucial to a carbon-neutral world. H2 generation by Chlamydomonas reinhardtii is an attractive approach for solar-H2 from H2O. However, it is currently not large-scalable because of lacking desirable strains with both optimal H2 productivity and sufficient knowledge of underlying molecular mechanism. We hereby carried out extensive and in-depth investigations of H2 photoproduction of hpm91 mutant lacking PGR5 (Proton Gradient Regulation 5) toward its up-scaling and fundamental mechanism issues. We show that hpm91 is at least 100-fold scalable (up to 10 L) with continuous H2 collection of 7287 ml H2/10L-HPBR in averagely 26 days under sulfur deprivation. Also, we show that hpm91 is robust and active during sustained H2 photoproduction, most likely due to decreased intracellular ROS relative to wild type. Moreover, we obtained quantitative proteomic profiles of wild type and hpm91 at four representing time points of H2 evolution, leading to 2229 and 1350 differentially expressed proteins, respectively. Compared to wild type, major proteome alterations of hpm91 include not only core subunits of photosystems and those related to anti-oxidative responses but also essential proteins in photosynthetic antenna, C/N metabolic balance, and sulfur assimilation toward both cysteine biosynthesis and sulfation of metabolites during sulfur-deprived H2 production. These results reveal not only new insights of cellular and molecular basis of enhanced H2 production in hpm91 but also provide additional candidate gene targets and modules for further genetic modifications and/or in artificial photosynthesis mimics toward basic and applied research aiming at advancing solar-H2 technology.

Aerobic Copper-Catalyzed Four-Component Reaction of O-Phenylenediamines, Isocyanides, and Selenium Powder for the Assembly of Benzo[4,5]imidazo[2,1-c][1,2,4]selenadiazol-3-imine Derivatives.

A convenient, four-component reaction of o-phenylenediamines, isocyanides, and selenium powder catalyzed by a natural abundant copper/air (O2) catalyst system has been developed, providing a highly step and atom economical protocol for the synthesis of benzo[4,5]imidazo[2,1-c][1,2,4]selenadiazol-3-imine derivatives with excellent yields and good functional group tolerance. This method enables the construction of an imidazo[2,1-c][1,2,4]selenadiazol ring, one N-Se bond, one C-Se bond, and three C-N bonds in a single step with only water as the byproduct. Preliminary mechanistic studies imply that the copper/air (O2)-catalyzed cyclization proceeds via a selenium-centered radical intermediate.

MnSO4-promoted S-O bond cleavage for synthesizing functionalized sulfonium ylides from activated alkynes and sulfoxides.

A variety of functionalized sulfonium ylides were prepared in good yields through MnSO4-promoted S-O bond cleavage from activated alkynes and sulfoxides. Experimental results showed that the MnSO4 catalyst played important roles in accelerating the reaction and promoting the [1,3]-rearrangement of the S-O bond. Furthermore, the product was easily obtained on a gram scale by simple recrystallization without column chromatography. The obtained product can be converted to new sulfonium ylides and undergo cycloaddition with an alkyne to afford a trisubstituted furan scaffold.

A receptor heteromer mediates the male perception of female attractants in plants.

Sexual reproduction requires recognition between the male and female gametes. In flowering plants, the immobile sperms are delivered to the ovule-enclosed female gametophyte by guided pollen tube growth. Although the female gametophyte-secreted peptides have been identified to be the chemotactic attractant to the pollen tube, the male receptor(s) is still unknown. Here we identify a cell-surface receptor heteromer, MDIS1-MIK, on the pollen tube that perceives female attractant LURE1 in Arabidopsis thaliana. MDIS1, MIK1 and MIK2 are plasma-membrane-localized receptor-like kinases with extracellular leucine-rich repeats and an intracellular kinase domain. LURE1 specifically binds the extracellular domains of MDIS1, MIK1 and MIK2, whereas mdis1 and mik1 mik2 mutant pollen tubes respond less sensitively to LURE1. Furthermore, LURE1 triggers dimerization of the receptors and activates the kinase activity of MIK1. Importantly, transformation of AtMDIS1 to the sister species Capsella rubella can partially break down the reproductive isolation barrier. Our findings reveal a new mechanism of the male perception of the female attracting signals.

Comparing the Efficacy of Intra-Articular Single Platelet-Rich Plasma(PRP) versus Novel Crosslinked Hyaluronic Acid for Early-Stage Knee Osteoarthritis: A Prospective, Double-Blind, Randomized Controlled Trial.

Background and Objectives: For the treatment of knee osteoarthritis (OA), intra-articular platelet-rich plasma (PRP) and novel crosslinked single-dose hyaluronic acid (HA) have both been reported to improve outcomes, but no study has compared them for the treatment of knee OA. We hypothesized patients with early-stage knee OA who received PRP injections would have more WOMAC score changes than those who received HA injections. This is the first prospective, double-blind, parallel, randomized controlled trial comparing the efficacy of intra-articular single-dose PRP versus novel crosslinked HA (HyajointPlus) for treating early-stage knee OA. Materials and Methods: This study analyzed 110 patients randomized into the PRP (n = 54) or HA (n = 56) groups. The primary outcome is the change of WOMAC score at 1-, 3-, and 6-month follow-ups compared to baseline. Results: The data revealed significant improvements in all WOMAC scores in the PRP group at 1-, 3-, and 6-month follow-up visits compared with the baseline level except for the WOMAC stiffness score at the 1-month follow up. In the HA group, significant improvements were observed only in the WOMAC pain score for all the follow-up visits and in WOMAC stiffness, function, and total scores at 6-month follow-up. When comparing the change of WOMAC score at 1-, 3-, and 6-month follow-ups, no significant differences were found between PRP and HA group. Conclusions: This study revealed that both PRP and HA can yield significant improvements in WOMAC scores at 6-month follow-up without any between-group differences at 1-, 3-, and 6-month follow-ups. Thus, both the single-injection regimens of PRP and HA can improve the functional outcomes for treating early-stage knee OA.

[Effects of Obstructive Sleep Apnea and Gender on Glomerular Filtration Rate in Hypertensive Population].

Objective To explore the associations of obstructive sleep apnea(OSA) and gender with estimated glomerular filtration rate(eGFR) in hypertensive populations.Methods From February 2005 to August 2010,2064 hypertensive patients who were treated in the Department of Hypertension Center underwent overnight polysomnographic monitoring.According to the apnea-hypopnea index(AHI),they were assigned into an hypertension combined with OSA group and a hypertension group.The clinical characteristics and sleep monitoring indicators were compared between different genders and between the two groups.Multivariate Logistic regression was employed to analyze the influencing factors of eGFR.Results Among the 2064 hypertensive patients,there were 1537 males(including 1221 patients with OSA) and 527 females(including 350 patients with OSA).The males had higher prevalence of OSA(χ2=36.631,P<0.001) and diastolic blood pressure(Z=-7.776,P<0.001) and lower eGFR(Z=-3.010,P=0.003) than the females.The males had higher AHI(Z=-8.727,P<0.001),apnea index(Z=-9.252,P<0.001),hypopnea index(HI)(Z=-4.868,P<0.001) than the females,and the lowest oxygen saturation(t=-3.325,P=0.001) was significantly lower in males than in females.The hypertension combined with OSA group showed lower eGFR than the hypertension group(Z=-27.434,P<0.001;Z=-18.762,P<0.001).HI was negatively correlated with eGFR in the male population(r=-0.006,P=0.017),and AHI and HI were negatively correlated eGFR in females(r=-0.108,P=0.013;r=-0.094,P=0.032).After adjustment,Logistic regression showed that OSA and oxygen desaturation index 4 were the risk factors for the reduction of eGFR in hypertensive patients in males and females,respectively(OR=1.383,95%CI=1.010-1.905,P=0.045;OR=1.013,95%CI=1.002-1.024,P=0.021).Conclusion OSA lowers the eGFR of hypertensive patients,and OSA and oxygen desaturation index are the risk factors for the decrease in eGFR in male and female hypertensive patients,respectively.

Palladium-catalyzed double coupling reaction of terminal alkynes with isocyanides: a direct approach to symmetrical N-aryl dialkynylimines.

A novel and efficient one-pot synthesis of symmetrical N-aryl dialkynylimines via palladium-catalyzed and copper-promoted isocyanide insertion, cross-coupling and elimination has been developed. This method features readily available starting materials, mild reaction conditions and high atom efficiency as well as simple one-pot operation, which make this strategy highly attractive. Moreover, 2-iodobenzo[f]quinoline derivatives can be obtained via electrophilic cyclization of N-aryl dialkynylimines.

Facile synthesis of 2-alkynyl oxazoles via a Ce(OTf)3-catalyzed cascade reaction of alkynyl carboxylic acids with tert-butyl isocyanide.

We developed an efficient and novel protocol to synthesize 2-alkynyl oxazoles from tert-butyl isocyanide and alkynyl carboxylic acids. This method allowed the synthesis of diversely functionalized oxazoles under mild reaction conditions, coupled with operational simplicity and these functionalized oxazoles showed a certain degree of biological activity. Moreover, compounds 2b, 2h, 2k, 2n, 2p and 2t exhibited good anticancer activities in human gastric cancer cells (MGC803) and human bladder tumor cells (T24), with IC50 below 20.0 µM.

Efficacy and Safety of Extracorporeal Shockwave Therapy for Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of extracorporeal shockwave therapy (ESWT) for treatment of knee osteoarthritis (OA) using a systemic review and meta-analysis. METHODS: An extensive search of relevant articles from electronic databases Pubmed, Embase, and Cochrane Library from inception to March 2019 was conducted. The treatment outcomes (visual analog scale [VAS] and the Western Ontario and McMaster Universities Arthritis Index [WOMAC]) of the included articles were pooled to calculate effect sizes. The assessment of heterogeneity among articles was evaluated using I2. Statistical analyses were conducted using RevMan software. RESULTS: The results showed that the ESWT group had significant improvement in pain relief compared with the control group through 12 months based on WOMAC and VAS scores. Compared with the baseline level, the patients had significant improvement in pain relief at most follow-up points (one week to 12 months) based on WOMAC and VAS scores. The patients showed significant improvement in physical function at six- and 12-month follow-up when compared with the control group and for all follow-up (one to 12 months) when compared with the baseline level. Additionally, only minor complications were observed after ESWT treatment. CONCLUSIONS: The use of ESWT for treatment of knee OA had a beneficial effect on pain relief and physical function improvement for up to 12 months, and only minor complications occurred after ESWT treatment. However, there remains a lack of clarity regarding the frequency and dosage levels of ESWT required to achieve the maximum improvement.

[GG Genotype at rs1275988 and rs2586886 Loci of TWIK-related Acid-sensitive K + Channel-1 Gene is A Potential Risk Factor for Severe Obstructive Sleep Apnea].

Objective To explore the mechanism of obstructive sleep apnea(OSA) by assessing the association between human TWIK-related acid-sensitive K + channel-1(TASK-1) gene and OSA. Methods A total of 164 patients with severe OSA and 171 patients without OSA were recruited from the Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region,China,from April to December 2016.Two single nucleotide polymorphisms(rs1275988 and rs2586886) in the TASK-1 gene were selected and genotyped using a Kompetitive Allele Specific PCR genotyping system. Results In patients with blood potassium <3.95 mmol/L,the distribution of rs1275988 alleles(G vs.A)(χ 2=4.474,P=0.034) and recessive model(GG+GA vs.AA)(χ 2=4.327,P=0.038) showed significant differences between severe and non-OSA groups.The distribution of rs2586886 alleles(G vs.A)(χ 2=6.345,P=0.012) and dominant model(AA+GA vs.GA)(χ 2=4.431,P=0.035) showed significant differences between severe and non-OSA groups.The Logistic regression analysis showed that the GG genotype was a risk factor for OSA patients with blood potassium <3.95 mmol/L(OR=7.854,95% CI:1.710-36.000,P=0.008;OR=8.849,95% CI:1.816-43.117,P=0.007). Conclusions Both the GG genotypes of rs1275988 and rs2586886 in the TASK-1 gene may be potential risk factors in severe OSA patients with blood potassium <3.95 mmol/L.Serum potassium>3.95 mmol/L in patients with TASK-1 GG genotype may be conducive to reducing the incidence of severe OSA.

Constituents from the Leaves of Tetraena mongolica and Their Protective Activity in HEK 293t Cells Damaged by CdCl2.

Tetraena mongolica Maxim, a relict originating from the Tertiary Period, is an endemic species of Zygophyllaceae in China. Three new monoterpenoids (1-3), two new phenols (4, 5) with unusual O-sulfoglucosyl groups, a new flavonoid (6), and nine known compounds were isolated from the leaves of T. mongolica. The structures of these compounds were determined by interpretation of NMR, MS, and ECD data. Some of the isolated compounds showed protective effects on HEK 293t cells damaged by CdCl2, with IC50 values being 55.7 and 80.3 µM for compounds 7 and 8, respectively, at the time point of 48 h after treatment.

Studies of Superb Microvascular Imaging and Contrast-Enhanced Ultrasonography in the Evaluation of Vascularization in Early Bone Regeneration.

OBJECTIVE: The aim of this study was to investigate value of superb microvascular imaging (SMI) and contrast-enhanced ultrasonography (CEUS) in evaluating the neovascularization of early bone regeneration. METHODS: Twenty-five Sprague-Dawley male rats were implanted with recombinant human bone morphogenetic protein-2/calcium phosphate cement (rhBMP-2/) in the muscle space of the left hind limb near the femoral head to establish the rat model of intramuscular ectopic osteogenesis. Ultrasonography and pathologic analysis were performed on the 3rd, 7th, 14th, 21st, and 28th days after modeling. Two-dimensional ultrasonography, SMI, and CEUS were used to assess neovascularization and bone formation. RESULTS: Pathologic examination showed that different levels of neovascularization were observed in the graft bone over time after modeling, which increased significantly from the 3rd to 14th day, and then gradually decreased. CEUS and SMI showed no obvious microvessels inside the graft bone on the 3rd day. On the 7th day after modeling, a small number of neovascular vessels were observed around the graft bone. On the 14th day, neovascularization was observed in both the peripheral and inner parts of the graft bone. The number of neovascular vessels inside the graft bone had decreased gradually by the 21st and 28th days. The results of SMI and CEUS indexes showed that the vascular index, peak intensity, enhancement intensity, and enhancement rate first increased and then decreased with time. Their peak points were found on the 14th day. Arrival time, time to peak, and enhancement time decreased gradually over time (P < .05). CONCLUSION: The combined application of SMI and CEUS may be useful in evaluating the neovascularization of early osteoanagenesis.

[Advances of the technologies in large-scale membrane proteome identification].

Membrane proteins play important functions not only as receptors and transporters, but also in many other important intracellular functions such as photosynthetic and respiratory electron transport. Identification of membrane proteins is a necessary step to understand their functions. Membrane proteins are generally highly hydrophobic and difficult to be resolved by aqueous solutions, and large-scale proteomic identification of membrane proteins has been a great technical challenge. Significant efforts have been invested in the field to improve the solubility of membrane proteins in aqueous solutions that are compatible for mass spectrometry analysis. This review summarizes the main technological achievements in the field of membrane proteomics particularly for the improvement of membrane protein identification, and uses the photosynthetic model cyanobacterium Synechocystis sp. PCC6803 as an example to illustrate how technology advances push forward the field in terms of the increased coverage of membrane proteome identification.

Praseodymium(III)-Catalyzed Regioselective Synthesis of C3-N-Substituted Coumarins with Coumarins and Azides.

A series of C3-N-substituted coumarins were synthesized in good yields directly from coumarins and azides in the presence of Pr(OTf)3 without any additives or ligands needed. The selected compounds 3a, 3c-e, 3g, 3i, 3q, 3u, and 3v exhibited good anticancer activities against MGC-803, A549, and NCI-H460 cell lines with IC50 in the range 8.75-38.54 µmol L-1.

The proteome and phosphoproteome of maize pollen uncovers fertility candidate proteins.

Maize is unique since it is both monoecious and diclinous (separate male and female flowers on the same plant). We investigated the proteome and phosphoproteome of maize pollen containing modified proteins and here we provide a comprehensive pollen proteome and phosphoproteome which contain 100,990 peptides from 6750 proteins and 5292 phosphorylated sites corresponding to 2257 maize phosphoproteins, respectively. Interestingly, among the total 27 overrepresented phosphosite motifs we identified here, 11 were novel motifs, which suggested different modification mechanisms in plants compared to those of animals. Enrichment analysis of pollen phosphoproteins showed that pathways including DNA synthesis/chromatin structure, regulation of RNA transcription, protein modification, cell organization, signal transduction, cell cycle, vesicle transport, transport of ions and metabolisms, which were involved in pollen development, the following germination and pollen tube growth, were regulated by phosphorylation. In this study, we also found 430 kinases and 105 phosphatases in the maize pollen phosphoproteome, among which calcium dependent protein kinases (CDPKs), leucine rich repeat kinase, SNF1 related protein kinases and MAPK family proteins were heavily enriched and further analyzed. From our research, we also uncovered hundreds of male sterility-associated proteins and phosphoproteins that might influence maize productivity and serve as targets for hybrid maize seed production. At last, a putative complex signaling pathway involving CDPKs, MAPKs, ubiquitin ligases and multiple fertility proteins was constructed. Overall, our data provides new insight for further investigation of protein phosphorylation status in mature maize pollen and construction of maize male sterile mutants in the future.