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Gold-catalyzed formal (3 + 2) and (4 + 2) cycloadditions of readily available alkynes using amino but/pent-2-enoate derivatives as annulating reagents were developed, furnishing highly functionalized 2,3-dihydropyrroles and 1,2,3,4-tetrahydropyridines.

Anti-dsDNA antibodies are pathogenically heterogeneous, implying distinct origins and antigenic properties. Unexpectedly, during the clinical and molecular characterization of autoantibodies to the endonuclease DNase1L3 in patients with systemic lupus erythematosus (SLE), we identified a subset of neutralizing anti-DNase1L3 antibodies previously catalogued as anti-dsDNA. Based on their variable heavy-chain (VH) gene usage, these antibodies can be divided in two groups. One group is encoded by the inherently autoreactive VH4-34 gene segment, derives from anti-DNase1L3 germline-encoded precursors, and gains cross-reactivity to dsDNA – and some additionally to cardiolipin – following somatic hypermutation. The second group, originally defined as nephritogenic anti-dsDNA antibodies, is encoded by diverse VH gene segments. Although affinity maturation results in dual reactivity to DNase1L3 and dsDNA, their binding efficiencies favor DNase1L3 as the primary antigen. Clinical, transcriptional and monoclonal antibody data support that cross-reactive anti-DNase1L3/dsDNA antibodies are more pathogenic than single reactive anti-dsDNA antibodies. These findings point to DNase1L3 as the primary target of a subset of antibodies classified as anti-dsDNA, shedding light on the origin and pathogenic heterogeneity of antibodies reactive to dsDNA in SLE.

Background Alpha‐kinase 1 (ALPK1) is a master regulator in inflammation and has been proved to promote renal fibrosis by promoting the production of IL-1β in diabetic nephropathy (DN) mice. Pyroptosis is involved in high glucose (HG)-induced tubular cells injury, characterized by activation of Gasdermin D (GSDMD) and the release of IL-1β and IL-18, resulting in inflammatory injury in DN. It is reasonable to assume that ALPK1 is involved in pyroptosis-related tubular injury in DN. However, the mechanism remains poorly defined. Methods Immunohistochemistry (IHC) staining was performed to detect the expression of pyroptosis- and fibrosis-related proteins in renal sections of DN patients and DN mice. DN models were induced through injection of streptozotocin combined with a high-fat diet. Protein levels of ALPK1, NF-κB, Caspase-1, GSDMD, IL-1β, IL-18 and α-SMA were detected by Western blot. HK-2 cells treated with high-glucose (HG) served as an in vitro model. ALPK1 small interfering RNA (siRNA) was transfected into HK-2 cells to down-regulate ALPK1. The pyroptosis rates were determined by flow cytometry. The concentrations of IL-1β and IL-18 were evaluated by ELISA kits. Immunofluorescence staining was used to observe translocation of NF-κB and GSDMD. Results The heat map of differentially expressed genes showed that ALPK1, Caspase-1 and GSDMD were upregulated in the DN group. The expression levels of ALPK1, Caspase-1, GSDMD and CD68 were increased in renal biopsy tissues of DN patients by IHC. ALPK1expression and CD68+ macrophages were positively correlated with tubular injury in DN patients. Western blot analysis showed increased expressions of ALPK1, phospho-NF-κB P65, GSDMD-NT, and IL-1β in renal tissues of DN mice and HK-2 cells, accompanied with increased renal fibrosis-related proteins (FN, α-SMA) and macrophages infiltration in interstitial areas. Inhibition of ALPK1 attenuated HG-induced upregulation expressions of NF-κB, pyroptosis-related proteins Caspase-1, GSDMD-NT, IL-1β, IL-18, α-SMA, and pyroptosis level in HK-2 cells. Also, the intensity and nuclear translocation of NF-κB and membranous translocation of GSDMD were ameliorated in HG-treated HK-2 cells after treatment with ALPK1 siRNA. Conclusions Our data suggest that ALPK1/NF-κB pathway initiated canonical caspase-1-GSDMD pyroptosis pathway, resulting in tubular injury and interstitial inflammation of DN.

α-Carbonyl cations are the umpolung forms of the synthetically fundamental α-carbonyl carbanions. They are highly reactive yet rarely studied and utilized species and their precursors were rather limited. Herein, we report the generation of α-carbonyl cations from HNTf2-catalyzed alkyne oxidations with pyridine N-oxides and the interception of them via Wagner-Meerwein rearrangement. Broad spectrum of alkynes including aryl alkyne, ynamide, and alkynyl sulfide could be utilized and the migrating priorities of different groups in the Wagner-Meerwein rearrangement step was elucidated. DFT calculations further supported the generation of α-carbonyl cations via the N-O bond cleavage. Another key feature of this methodology was the fragmentation of synthetically inert tert-butyl groups into readily transformable olefin functionalities. The synthetic potential was highlighted by the scale-up reaction and the downstream diversifications including the formal synthesis of nicotlactone B and galbacin.

We report a comprehensive DFT study on gold-catalyzed domino cyclization to spiroindolines.

The triangular libration points in the Earth-Moon system are considered to be potential candidates for future space missions because of their unique positions and dynamics. This paper presents a comprehensive transfer trajectory design and optimization framework for transfers from the Earth to L 4 in the Earth-Moon system, including direct transfer and transfer utilizing powered lunar gravity assist. In this framework, first, a synthetic procedure combining an initial guess, a differential correction algorithm and numerical continuation for generating tangential transfer families is illustrated. Subsequently, the optimization models for optimal transfer trajectories with the minimum velocity increment requirement are constructed. For direct transfer, the optimal direct transfer trajectory is obtained using primer vector theory. For the optimal transfer utilizing powered lunar gravity assist under a minimum swing-by height constraint, the necessary optimality conditions are found through optimal control theory, and an optimization procedure that allows for numerical convergence to the optimal solution is constructed. Numerical results indicate that the proposed transfer trajectory design and optimization framework has sufficient effectiveness to provide various transfer trajectories associated with different insertion points and fuel-optimal transfers.

A gold-catalyzed formal dipolar cycloaddition reaction was developed using polarized alkynes as dipolarophiles and butenediol or pentenediol derivatives as formal dipoles. Silyl groups were used to solve the selectivity issue of unsymmetrical diols.

Corrosion not only causes a lot of economic losses, but possibly threatens personal safety. The superhydrophobic polyaniline composite anti-corrosion coating (SPANC) has closely received attention ...

Diaryliodonium salts have been extensively applied in organic synthesis as aryl cation equivalents. However, in the electrophilic reactions with alkenes or alkynes, only the electrophilic carbon of the diaryliodonium salts was involved while the other part of the aryl ring was not utilized. Herein, a reaction pattern of diaryliodonium was reported as oxa-1,4-dipoles to undergo (4 + 2) cycloaddition reactions with alkynes. Broad spectrum of the two reaction partners could be utilized in this protocol, enabling an operationally simple, high yielding, and regioselective synthetic approach to isocoumarins. Particularly, good to excellent regioselectivities were achieved for the sterically unbiased unsymmetrical diaryl acetylenes, which was challenging for other transition metal-catalyzed processes. The reaction could be scaled up with the ideal 1:1 stoichiometry and the isocoumarin type natural products Oospolactone and Thunberginol A could be obtained in one or three steps through this methodology.

The dynamics of SARS-CoV-2 RNA structure and their functional relevance are largely unknown. Here we develop a simplified SPLASH assay and comprehensively map the in vivo RNA-RNA interactome of SARS-CoV-2 genome across viral life cycle. We report canonical and alternative structures including 5′-UTR and 3′-UTR, frameshifting element (FSE) pseudoknot and genome cyclization in both cells and virions. We provide direct evidence of interactions between Transcription Regulating Sequences, which facilitate discontinuous transcription. In addition, we reveal alternative short and long distance arches around FSE. More importantly, we find that within virions, while SARS-CoV-2 genome RNA undergoes intensive compaction, genome domains remain stable but with strengthened demarcation of local domains and weakened global cyclization. Taken together, our analysis reveals the structural basis for the regulation of replication, discontinuous transcription and translational frameshifting, the alternative conformations and the maintenance of global genome organization during the whole life cycle of SARS-CoV-2, which we anticipate will help develop better antiviral strategies., RNA secondary structure is important for viral replication, transcription and translation. Here the authors employ SPLASH method and map in vivo RNA interactions and dynamics of SARS-CoV-2 RNA genome in different viral life cycles.

The flowerlike copper sulfide (CuS)/reduced graphene oxide (rGO) composites were prepared successfully by the hydrothermal method. The active anodic material was characterized by Raman spectroscopy, thermogravimetric analyses (TGA), transmission electron microscopy (TEM), and electrochemical techniques. TEM images showed that the flowerlike CuS is well combined with rGO. The electrochemical tests indicate that the presence of rGO improves the electrochemical performance of the CuS, achieving an initial high discharge capacity of 3401 mAh g−1 and initial charge capacity of 1064 mAh g−1, superior to that exhibited for pure CuS (765.2 mAh g−1 and 318.9 mAh g−1). The reason for this is that the addition of rGO increases the surface area and conductivity of the material. The changes enable the composite material more effectively to adapt to the severe volume changes during charging and discharging.

Elliptical elements are essential optical surfaces for modifying optical systems. For polishing the whole elliptical surface using doughnut-shaped MCF polishing tool with variable tilt angle, an experimental investigation was conducted in this work. Firstly, a flat workpiece was polished to determine the polishing feasibility. It was found that the middle portion of the polishing tool had optimal ability to remove materials, and the surface roughness Sa at the material removal peak was changed from 134 nm to 17.5 nm within 50 min of polishing. A smoother surface could be obtained using MCF2 slurry and MCF3 slurry, but the use of MCF1 slurry resulted in a rough surface. Then, the effects of working gap h, revolution speed of MCF polishing tool and polishing time on the polishing results were tested to study the polishing characteristics. Sa 9.6 nm and glossiness 278 Gu were obtained, and form error improved from 2.3 μm to 1.3 μm. Finally, the MCF polishing tool was dried to observe the microstructure of the MCF polishing tool after polishing. Abrasive particles were distributed evenly after polishing. It was seen that the abrasive particles were grabbed by the ferric clusters, and the α-celluloses were interleaved between the clusters.

Herein, a new reaction pattern of diaryliodonium salts was reported as novelty oxa-1,4-dipoles to undergo [4+2] cycloaddition reactions with alkynes. Broad spectrum of the two reaction partners could be utilized in this protocol, enabling an operationally simple, high yielding, and regioselective synthetic approach to isocoumarins. Particularly, good to excellent regioselectivities were achieved for the sterically unbiased unsymmetrical diaryl acetylenes, which was challenging for other transition metal-catalyzed processes. The reaction could be scaled up with the ideal 1:1 stoichiometry and the isocoumarin type natural products Oospolactone and Thunberginol A could be obtained in one or three steps through this methodology.

MYCNOS is an oncogenic lncRNA in liver cancer, but its role in glioblastoma (GBM) is unknown. We predicted that MYCNOS might interact with miR-216b, which targets FOXM1 to perform tumor suppressive roles. This study was performed to analyze the role of MYCNOS in GBM and explore its potential interactions with miR-216b and FOXM1. MYCNOS expression in paired GBM and non-tumor tissues from 62 GBM patients was analyzed by RT-qPCR. The interaction between MYCNOS and miR-216b was predicted by IntaRNA 2.0 and confirmed by dual luciferase activity assay. Overexpression of MYCNOS, miR-216b, and FOXM1 was achieved in GBM cells, followed by performing RT-qPCR and Western blot to explore the relationship among them. CCK-8 assay was performed to explore the role of MYCNOS, miR-216b, and FOXM1 in regulating GBM cell proliferation. MYCNOS was upregulated in GBM tissues compared to the paired non-tumor tissues. MYCNOS is predicted to interact with miR-216b, but overexpression of MYCNOS and miR-216b failed to affect each other's expression significantly. Dual luciferase activity assay showed that MYCNOS and miR-216b could directly interact with each other. MYCNOS overexpression increased the expression of FOXM1, which is a direct target of miR-216b. Cell proliferation assay showed that MYCNOS and FOXM1 overexpression resulted in an increased proliferation rate of GBM cells, while miR-216b overexpression suppressed cell proliferation. Moreover, MYCNOS overexpression suppressed the role of miR-216b. MYCNOS may regulate FOXM1 expression of by serving as an endogenous sponge of miR-216b axis to promote the proliferation of GBM cells.

In this work, a novel N-doped magnetic mesoporous carbon (NMC) composite (Fe3O4/NMC) was synthesized by a two-step process. First, NMC was prepared by a template method using a melamine formaldehyde resin as nitrogen and carbon sources, and then, Fe3O4 nanoparticles were loaded into the as-prepared NMC via in-situ coprecipitation process. The morphology, structure, and magnetic properties of Fe3O4/NMC were characterized and its adsorption properties were investigated. It can be found that Fe3O4/NMC with saturation magnetization of 20 emu · g−1 features a mesoporous structure, and its specific surface area reaches 513 m2 · g−1. These two excellent specificities are propitious to the adsorption and separation of Ag(I) from aqueous solution. The adsorption behavior of Fe3O4/NMC nanocomposite has been investigated by adsorption kinetics and isotherms adsorption analyses as well. The adsorption isotherm and the adsorption kinetics of Ag(I) onto Fe3O4/NMC agrees well with Langmuir model and pseudo-second-order model, respectively. Moreover, the Fe3O4/NMC was easily to recovery by applied magnetic field, the adsorption capacity of Fe3O4/NMC was about 90.3% of the initial saturation adsorption capacity after five continuous uses.

Gold nanoparticles (GNPs) are widely used in life sciences and medicine due to their simple preparation, stable physical and chemical properties, controllable optical properties and no significant toxicity. However, in recent years, studies have found that there are still many uncertain factors in the application of gold nanoparticles in the field of biomedicine, and there are few studies on the main excretion organs and kidneys of the body, especially the toxicological effects under the disease state have not been reported. Obviously, carrying out relevant research is of great significance for accelerating the clinical application of GNPs. Chronic kidney disease (CKD) is a group of chronic progressive diseases that have high prevalence and high mortality and are serious threats to human life and health. Renal tubular injury and interstitial fibrosis are key factors in renal dysfunction in chronic kidney disease. Drug and toxic kidney damage mostly involve renal tubular epithelial cells; hypoxia is the most common pathological condition of cells. In renal lesions, renal tubular epithelial cells often have hypoxia. Based on this, we propose the hypothesis of this study: glomerular filtration membrane damage in kidney disease, GNPs increase in urine, followed by reabsorption of renal tubular epithelial cells, thereby causing damage to the latter; if accompanied by hypoxia, GNPs it will aggravate renal tubular epithelial cell damage and promote tubulointerstitial fibrosis. In order to verify the above hypothesis, this study used a mouse model of adriamycin nephropathy and tubular epithelial cells and macrophages in vitro, and observed the damage of GNPs on renal tubular epithelial cells by various means, and explored related mechanisms. The results show that under normal oxygen conditions, GNPs can induce autophagy after cell entry, which can damage damaged proteins and organelles to maintain cell survival. In the absence of oxygen, nanoparticles entering cells increase and induce excessive autophagy. In the absence of oxygen, GNPs also aggregate in macrophages, which can cause decreased cell proliferation activity and induce activation of macrophage inflammasome, which induces inflammatory response: GNPs-induced secretion of hypoxic macrophages can be promoted.

Zirconia ceramics have excellent applicability in the aerospace, defense, new energy, automotive, electronics, and biomedical fields. However, few investigations have been conducted on the high-precision polishing of zirconia ceramics. In this work, a polishing method using a magnetic compound fluid slurry is proposed. First, the principle and the constructed experimental setup were presented. Then, the experiments were performed that characterized the surface profile after polishing, the effect of the working gap, and the effect of the concentration of carbonyl iron particles (CIPs) on the material removal and surface quality. The results showed that the material removal ability correlated positively with the surface roughness; the smallest working gap (0.5 mm) induced greater material removal ability and better surface roughness; higher CIP concentration enabled a higher polishing force to obtain higher material removal and better surface quality. The polishing results show that surface roughness Rz of 55 nm was obtained at the surfaces of zirconia ceramics, confirming that the proposed method has the potential for polishing of zirconia ceramics.

The ZnS/C composites with different carbon coating contents were successfully prepared using the solvothermal method followed by the calcination process. The obtained ZnS/C composites were characterized by XRD, SEM, and TEM. The results indicate that the morphology of 50 wt% carbon-coated ZnS/C composites possesses uniform spheres with a size of 80 nm, and the thickness of the carbon layer is 8 nm. When the prepared composites were used as anode materials for lithium-ion batteries (LIBs), the electrode made by 50 wt% carbon-coated ZnS/C composites shows an excellent initial discharge capacity of 1189.8 mAh/g, high discharge capacity of 948.9 mAh/g at a current rate of 0.1 C after 50 cycles, good cycling stability, and excellent rate capability of 744.8 mAh/g at 2.0 C. The excellent electrochemical performances make the nanosized ZnS/C composites a promising candidate for the LIBs.

Herein, we report the first diaryliodonium salts promoted multicomponent 1,2,3-trifunctionalization of alkynes, where both the acetylenic bond and the adjacent nonactivated propargylic C(sp

Toll-like receptor 4 (TLR4) mediated pathway plays a pivotal role in promoting tubulointerstitial inflammation and contributes to the progression in type 2 diabetic kidney disease (T2DKD). As the first identified key pyroptosis executor, gasdermin D (GSDMD) is activated by caspases and might be the key protein to switch apoptosis to pyroptosis. It remains unclear that role of TLR4 on canonical pyroptosis pathway, and whether GSDMD is involved in switching from apoptosis to pyroptosis in the TLR4-related tubular injury in T2DKD.Immunohistochemistry staining was used to detect the expression of pyroptosis-related proteins in renal tissues of T2DKD patients. T2DKD models was induced in TLR4 knockout (TLR4The expression levels of caspase-1, GSDMD, IL-18 and IL-1β were increased in renal biopsy tissues of T2DKD patients and GSDMD expression was positively correlated with tubular injury. Silencing GSDMD attenuated HG-induced IL-18, IL-1β, FN and α-SMA, and reduced pyroptotic cells rate in HK-2 cells. Up-regulation of GSDMD inhibited HG-induced expression of Bax and cleaved caspase-3 and reduced apoptosis rate. TLR4 knockout alleviated tubular injury and interstitial macrophages infiltration, improved impaired renal dysfunction, and decreased the expressions of active N-terminal of GSDMD(GSDMD-N), cleaved caspase-1(cl-caspase-1) and cleaved caspase-3(cl-caspase-3) in T2DKD mice. TLR4 inhibition reduced HG-induced pyroptosis and apoptosis level in HK-2 cells, while GSDMD up-regulation increased pyroptosis rate and decreased apoptosis rate.TLR4 could exacerbate tubular injury and fibrosis via GSDMD-mediated canonical pyroptosis pathway in T2DKD. Activation of GSDMD could inhibit apoptosis and activate pyroptosis, which may involve the potential switch mechanism between TLR4-mediated pyroptosis and apoptosis in T2DKD.

For the aspheric optical surface finished with a doughnut-shaped MCF (magnetic compound fluid) polishing tool, the performance of the polishing tool depends mainly on the properties of the MCF slurry. Therefore, understanding the effect of each MCF slurry component on the polishing characteristics is crucial to developing novel polishing techniques. In this paper, the polishing principle was depicted and the corresponding polishing jig was constructed with a six-degree-of-freedom manipulator. The conical surfaces, which were considered as special aspheric surfaces, were experimentally polished under proper polishing conditions to examine the effects of the carbonyl iron particles (CIPs) concentration and the sizes of the abrasive particles (APs) on the polishing ability to remove material/tool marks and improve work surface qualities. Theoretical analyses were also performed to gain a more comprehensive understanding of the behaviors of CIPs and APs in the magnetic field. The results were shown as follows: (1) The CIPs concentration affected positively the magnetization of the MCF slurry, leading to better performance in the removal rate of material/tool marks when a higher CIPs concentration of was applied. The best surface quality was attained with a CIPs concentration of 45 wt%. (2) Larger APs were beneficial for obtaining higher removal rates of material/tool marks. The APs with 1 μm in diameter were preferred for achieving a better surface quality. (3) Ferric clusters were formed along the magnetic line of force and their orientations changed periodically to stir the APs with the magnet revolution. (4) The Aps, at a given working gap, can squeeze the work-surface. The squeezing action was much more intense when larger APs and the MCF slurry with a higher magnetization were employed. (5) The material removal model suggested that the material was removed due to the APs and the relative motion between the work-surface and APs.

Quaternary carbon stereocenters are ubiquitous in a wide variety of organic compounds and drug molecules. Highly enantioselective construction of such quaternary carbon centers poses a singular cha...

The palladium-catalyzed unified approach using in situ-generated Phospha-TMM species to synthesize a diverse array of chiral organophosphorus containing carbo- and heterocyclic compounds in a highly regio-, diastereo- (>20:1 dr), and enantioselective (>99% ee) fashion is being disclosed. The present protocol reveals the potential of the deprotonative phospha-TMM strategy for the synthesis of challenging five-membered carbo- and heterocycles, especially those with spirocyclic entities and quaternary asymmetric stereocenters. The choice of the robust chiral diamidophosphite ligand proved to be very crucial for the desired reactivity in the present transformation. Furthermore, the synthetic utility of the products is demonstrated by multiple transformations such as reductions, oxidations, and alkylations.

Aspheric elements have become essential optical surfaces for modifying optical systems due to their abilities to enhance the imaging quality. In this work, a novel method employing a doughnut-shaped magnetic compound fluid (MCF) polishing tool, and an industrial robot was proposed for polishing aspheric surfaces. Firstly, investigations on the MCF tool, including the formation process and geometry, were conducted to form an appropriate polishing tool. The distribution of abrasive particles was observed using SEM and EDX mapping. Thereafter, a conic workpiece constructed from 6061-aluminum alloy was selected as the workpiece, which was used to discover the effects of the parameters on the polishing ability of aspheric surfaces. Finally, a polishing experiment was conducted with an aspheric element under the optimized conditions. The obtained results are shown as follows. (1) A relatively regular MCF tool was obtained when the eccentricity (r), amount of MCF slurry supplied (V), revolution speed of the MCF carrier and magnet (nc and nm, respectively) were given at appropriate values. (2) Abrasive particles entrapped in or attached to the clusters were observed abundantly on the MCF tool sample. (3) The surface profile of the conic workpiece after 60 min of polishing indicated that material was removed evenly, and an annular polishing area was attained. Meanwhile, a higher material removal rate and better surface roughness were achieved with a smaller working gap (h) and larger volume of the MCF slurry supplied (V). (4) The roughness (Ra) of the aspheric surface decreased from 49.81 to 10.77 nm after 60 min of polishing. The shape retention obtained a Pearson correlation coefficient (Pcc) of 0.9981, which demonstrated that this novel method is appropriate for polishing aspheric elements.

Tumor endothelial marker 8 (TEM8), also known as ANTXR1, was highly expressed in cancers, and was identified as a biomarker for early diagnosis and prognosis in some cancers. However, the clinical role and molecular mechanisms of TEM8 in lung adenocarcinoma (LUAD) are still unclear. The present study aimed to explore its clinical value and the molecular mechanisms of TEM8 underlying the progression of LUAD. Our study found the elevation of TEM8 in LUAD cell lines and tissues. What’s more, we observed that the TEM8 expression level was associated with tumor size, primary tumor, and AJCC stage, and LUAD patients with high TEM8 expression usually have a poor prognosis. Then, we conducted a series of experiments by the strategy of loss-of-function and gain-of-function, and our results suggested that the knockdown of TEM8 suppressed proliferation, migration, and invasion and induced apoptosis in LUAD whereas overexpression of TEM8 had the opposite effect. Molecular mechanistic investigation showed that TEM8 exerted its promoting effects mainly through activating the Wnt/β-catenin signaling pathway. In short, our findings suggested that TEM8 played a crucial role in the progression of LUAD by activating the Wnt/β-catenin signaling pathway and could serve as a potential therapeutic target for LUAD.

Magnetic field-assisted magnetic compound fluid (MCF) ultra-precision machining technology is regarded as an effective method to obtain a smooth surface. However, due to the evaporation and splashing of water in the polishing fluid during processing, the service life of the MCF slurry is reduced. This paper presents a material removal model for MCF polishing, and a novel experimental apparatus is proposed to extend the service life by supplying MCF components into the MCF slurry. Firstly, in order to obtain the ideal polishing tool, the appearance morphologies and the formation process of the MCF slurry were observed by an industrial camera. On this basis, the optimum parameters were determined by multi-factor and multi-level orthogonal experiments. Finally, the investigation of the MCF service life was carried out under the optimal processing parameters. The main findings are summarized as follows. (1) Excellent MCF polishing tools are obtained when the eccentric distance r is 4 mm and the MCF slurry supply V is 1 mL. (2) When the eccentric distance increases from 2 mm to 4 mm, the forming time of the MCF tool decreases sharply, but when the eccentricity exceeds 4 mm, the decreasing trend becomes slow. The molding time grows steadily as the supply is increased. (3) When the machining gap Δ, the MCF carrier speed nc, the eccentricity r, and the revolution speed of magnetic nm are 1 mm, 500 rpm, 4 mm, and 600 rpm, respectively, the ideal machining effect can be obtained. (4) It could be proven that the polishing device is feasible to extend the service time of the MCF slurry by adding MCF components.

Vinyl triflimides were only accessible recently and their chemistry is yet to be discovered. Herein, we describe a general, straightforward and atom-economical synthesis of these materials from alkynes and triflimide. A vast array of terminal and internal alkynes with broad spectrum of functionalities could be employed to generate various di- and trisubstituted vinyl triflimides regiospecifically with high to specific stereoselectivity. Moreover, the protocol could be conducted on gram scale using terminal and internal alkynes. Preliminarily attempts to probe the unknown reactivity of vinyl triflimides revealed part of its chemical properties.

We aim to find a biomarker that can effectively predict the prognosis of patients with cutaneous melanoma (CM). The RNA sequencing data of CM was downloaded from The Cancer Genome Atlas (TCGA) database and randomly divided into training group and test group. Survival statistical analysis and machine-learning approaches were performed on the RNA sequencing data of CM to develop a prognostic signature. Using univariable Cox proportional hazards regression, random survival forest algorithm, and receiver operating characteristic (ROC) in the training group, the four-mRNA signature including CD276, UQCRFS1, HAPLN3, and PIP4P1 was screened out. The four-mRNA signature could divide patients into low-risk and high-risk groups with different survival outcomes (log-rank p < 0.001). The predictive efficacy of the four-mRNA signature was confirmed in the test group, the whole TCGA group, and the independent GSE65904 (log-rank p < 0.05). The independence of the four-mRNA signature in prognostic prediction was demonstrated by multivariate Cox analysis. ROC and timeROC analyses showed that the efficiency of the signature in survival prediction was better than other clinical variables such as melanoma Clark level and tumor stage. This study highlights that the four-mRNA model could be used as a prognostic signature for CM patients with potential clinical application value.

Tumor endothelial marker 8 (TEM8), also known as ANTXR1, was highly expressed in cancers, and was identified as a biomarker for early diagnosis and prognosis in some cancers. However, the clinical role and molecular mechanisms of TEM8 in lung adenocarcinoma (LUAD) are still unclear. The present study aimed to explore its clinical value and the molecular mechanisms of TEM8 underlying the progression of LUAD. Our study found the elevation of TEM8 in LUAD cell lines and tissues. What’s more, we observed that the TEM8 expression level was associated with tumor size, primary tumor, and AJCC stage, and LUAD patients with high TEM8 expression usually have a poor prognosis. Then, we conducted a series of experiments by the strategy of loss-of-function and gain-of-function, and our results suggested that the knockdown of TEM8 suppressed proliferation, migration, and invasion and induced apoptosis in LUAD whereas overexpression of TEM8 had the opposite effect. Molecular mechanistic investigation showed that TEM8 exerted its promoting effects mainly through activating the Wnt/β-catenin signaling pathway. In short, our findings suggested that TEM8 played a crucial role in the progression of LUAD by activating the Wnt/β-catenin signaling pathway and could serve as a potential therapeutic target for LUAD.

BackgroundHuman papillomavirus type 39 associated with genital intraepithelial neoplasia and invasive cancers, has a high prevalence in Southwest China. HPV E6, E7 are two main papillomavirus oncoproteins, closely relate to the function of HPV immortalization, cell transformation, and carcinogenesis. L1 is the major capsid protein, can reflect the replication status of the virus in cells and the progression of cervical lesions. The purpose of this study is to reveal the prevalence of HPV 39 and the genetic polymorphisms of HPV39 based onE6, E7andL1gene in southwest China.MethodsCell samples were collected by cervical scraped for HPV detecting and typing, and HPV39 positive samples were selected out. ImportantE6, E7andL1genes of HPV39 were sequenced and analyzed for the study of HPV39 genetic polymorphisms. Phylogenetic trees were constructed by Maximum-likelihood and Kimura 2-parameters methods in Molecular Evolutionary Genetics Analysis version 6.0. The selection pressures ofE6, E7andL1genes were estimated by Datamonkey web server. The secondary and three-dimensional structure of HPV39 E6, E7 proteins were created by sopma server and SWISS-MODEL software.Results344 HPV39 positive samples were selected from 5718 HPV positive cell samples. Among HPV39E6-E7sequences, 20 single nucleotide mutations were detected, including 10 non-synonymous and 10 synonymous mutations; 26 single nucleotide mutations were detected in HPV39L1sequences, including 7 non-synonymous and 19 synonymous mutations respectively. 11 novel variants of HPV39E6-E7(5 inE6and 6 inE7) and 14 novel variants of HPV39L1were identified in this study. A-branch was the most frequent HPV39 lineage in southwest China during our investigation. Selective pressure analysis showed that codon sites 26, 87, 151 inE6and 75, 180, 222, 272, 284, 346, 356 inL1were positively selected sites, as well as codon sites 45, 138, 309, 381 were negative selection sites inL1gene,E7has neither positive selection sites nor negative selection sites. A certain degree of secondary and three-dimensional structure dislocation was existed due to the non-synonymous mutations.ConclusionsAmino acid substitution affected the secondary and three-dimensional structure of HPV39, and resulting in the differences of carcinogenic potential and biological functions as well as the immune response due to the antigen epitopes difference, the antigen epitopes with stronger adaptability in Southwest will be screened out based on the above research results for the later vaccine development. And gene polymorphism of HPV39 in Southwest China may improve the effectiveness of clinical test and vaccine design, specifically for women in Southwest China.

A field study on fog chemistry and aqueous-phase processing of aerosol particles was conducted in Fresno, California's San Joaquin Valley (SJV) during wintertime. Fog droplets were collected while interstitial submicron aerosol was characterized in real time using a High Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-AMS). The fog samples were later analyzed using HR-AMS, ion chromatography (IC), and total organic carbon analyzer (TOC). Compared to interstitial aerosol, dissolved solutes in fog waters were composed of higher fractions of ammonium, nitrate, sulfate, methanesulfonic acid, and oxygenated organic compounds, likely due to aqueous formation of secondary species as well as enhanced gas-to-particle partitioning of water-soluble gases under humid conditions. The low-volatility dissolved organic matter in fog water (F-OA) was moderately oxidized with an average oxygen-to-carbon (O/C) ratio of 0.42. The chemical composition of F-OA appeared to be overall similar to that of oxygenated organic component in interstitial aerosol (OOA) and the HR-AMS mass spectra of F-OA and OOA are highly similar (r2 > 0.95). However, there are also significant chemical differences as F-OA appeared to contain a larger fraction of carboxylic functional groups than OOA, indicating enhanced organic acid formation through aqueous-phase reactions. In addition, F-OA was composed of substantially more nitrogen-containing compounds, with an average N/C ratio ∼4 times that of OOA. Most strikingly was that the F-OA spectra showed substantial enhancements of the CxHyN2+ (x ≥ 0; y ≥ 0) ions, which were likely contributed by imidazole- and/or pyrazine-based compounds formed from the aqueous reactions of aldehydes with amino compounds. The results of this study demonstrated that aqueous reactions in atmospheric droplets can significantly modify aerosol composition and contribute to the formation of oxygenated and nitrogen-containing organic compounds in atmospheric aerosol particles. This finding is important for understanding aerosol's effects on human health, air quality, and climate.

： Graphene from chitosan (CG) with wrinkle, few layers and specific defects was prepared via a simple method of low carbonization temperature and high KOH activation temperature. At the activation temperature of 1100 °C, the obtained CG-1100 has the specific surface of 1212 m2·g−1 and the total volume of 1.02 cm3·g−1 at the optimized activation temperature. The results show that the CG-1100 is similar to another two graphenes: graphene nanoparticles (GNP) and multilayer graphene powders (MGP), which contain less defects. The Cu/CG-1100 composite photocatalyst was prepared from CG-1100 and Cu(Ac)2 solution with surface plasmon resonance (SPR) effect by in-situ synthesis method under illumination. When the binary composite contains 10 wt% of Cu NPs, the hydrogen evolution rate of Cu/CG-1100 photocatalyst reached 3.94 mmol·g−1·h−1, which is 3.2 times as high as that of pure Cu NPs. Interestingly, the defect sites of the graphene can influence the photocatalytic hydrogen production rate which was observed by depositing Cu NPs on GNP and MGP. The results showed that more defects on the graphene presented higher photocatalytic hydrogen evolution rate.

The fatigue damage model based on theory of damage mechanics is capable of predicting the fatigue life under multiaxial loading. Meanwhile, the application of critical plane method in the prediction of multiaxial fatigue life has made certain progress. According to the law of thermodynamics, a new damage evolution equation is developed in the present study to predict the fatigue life of geometrically discontinuous structure under tension-torsion loading based on damage mechanics and the critical plane method. The essence of this approach is that the strain parameter of the uniaxial nonlinear fatigue damage model is replaced with the equivalent strain, which consists of the relevant parameters of the critical plane. However, it is difficult to calculate the stress–strain status and the critical plane position of geometrically discontinuous structure by theoretical methods because of the existence of stress concentration and the multiaxial nonproportional characteristics. Therefore, a new numerical simulation method is proposed to determine the critical plane of geometrically discontinuous structure under multiaxial loading by means of the finite element method and MATLAB software. The fatigue life of notched specimens subjected to combined bending and torsion is predicted using the proposed method, and the result is compared with those from the experiments and the Manson–Coffin law. The comparisons show that the proposed method is superior to the Manson–Coffin law and is capable of reproducing the experimental results reasonably when the geometry of the structure is complex. It completely meets the needs of engineering practice.

A highly regio-, diastereo-, and enantioselective trimethylenemethane (TMM) cycloaddition reaction for the rapid assembly of 2-acyl-methylenecyclopentane in an atom-economic fashion is described. This intermolecular protocol allows for facile and divergent access to an array of structurally attractive cyclic adducts. The choice of a robust chiral diamidophosphite ligand, developed by our group, proved to be crucial for the success of this transformation.

Purpose: This study aimed to evaluate the effect of continuous clustered care on the physical growth of preterm infants and on the satisfaction with the nursing care. Methods: 120 preterm infants who were admitted to our hospital from Jan 2018 to Dec 2018 were recruited as the study cohort. These infants were randomly divided into a control group (n=60, routine care) and an experimental group (n=60, continuous clustered nursing care). The study compared the parenting skills in the two groups, the infant development at 6 and 12 months, the prevalence of diseases within one year after discharge, and the parents’ satisfaction with the nursing care. Results: There was no significant difference in the parenting skill levels between the two groups. The body masses, heights, and head circumferences of the infants at 6-months and 12-months in the experimental group were better than they were in the control group. The experimental group’s physical and intellectual development were significantly better than the physical and intellectual development in the control group (P

The PI3K/AKT/mTOR signaling pathway is constitutively active in PTEN-deficient cancer cells, and its targeted inhibition has significant anti-tumor effects. However, the efficacy of targeted therapies is often limited due to drug resistance. The relevant signaling pathways in PTEN-deficient cancer cells treated with the PI3K/mTOR inhibitor BEZ235 were screened using a phosphokinase array, and further validated following treatment with multiple PI3K/AKT/mTOR inhibitors or AKT knockdown. The correlation between PTEN expression levels and STAT3 kinase phosphorylation in the tissue microarrays of gastric cancer patients was analyzed by immunohistochemistry. Cell proliferation and clonogenic assays were performed on the suitably treated PTEN-deficient cancer cells. Cytokine arrays, small molecule inhibition and knockdown assays were performed to identify related factors. PTEN-deficient tumor xenografts were established in nude mice that were treated with PI3K/AKT/mTOR and/or STAT3 inhibitors. PTEN deficiency was positively correlated with low STAT3 activity. PI3K/mTOR inhibitors increased the expression and secretion of macrophage migration inhibitory factor (MIF) and activated the JAK1/STAT3 signaling pathway. Both cancer cells and in vivo tumor xenografts showed that the combined inhibition of PI3K/AKT/mTOR and STAT3 activity enhanced the inhibitory effect of BEZ235 on the proliferation of PTEN-deficient cancer cells. Our findings provide a scientific basis for a novel treatment strategy in cancer patients with PTEN deficiency.

A novel and efficient route is proposed to fabricate Fe3O4/polypyrrole (Fe3O4/PPy) nanotubes via a one-pot process. The one-pot strategy involves the synthesis of Fe3O4/PPy nanotubes by oxidative polymerization of pyrrole (Py) monomer using Fe3+ as an oxidant in the presence of methyl orange (MO) and Fe3+ used as iron source to form Fe3O4 simultaneously in basic conditions without adding any additional iron source and oxidant. The effects of Fe3+ concentration on the morphology and adsorption capacity of the Fe3O4/PPy nanotubes were investigated. The Fe3O4/PPy nanotubes exhibit a tubular structure. Fe3O4 nanoparticles are well dispersed among the PPy nanotubes. The Fe3O4/PPy nanotubes exhibit excellent magnetic property, which make them easy to separate from wastewater by magnetic separation. The diameter of the PPy nanotubes decreased with the increase of the Fe3+ concentration. The Fe3O4/PPy nanotubes showed strong adsorption capability for Cr(VI) with the maximum adsorption capacity of about 451.45 mg·g−1, which is significantly higher than bare Fe3O4 nanoparticles. Cr(VI) was adsorbed on Fe3O4/PPy nanotubes by ion exchange and chelation, where Cr(VI) was partially reduced to Cr(III) due to the existence of −NH+ on the Fe3O4/PPy nanotubes. Furthermore, the Fe3O4/PPy nanotubes are recyclable, retaining 90% of the initial removal efficiency after 5 adsorption/desorption cycles.

To evaluate the value of thrombospond in Type I domain-containing 7A (THSD7A) and M-type phospholipase A2 receptor (PLA2R) in primary membranous nephropathy (PMN) and to explore the relationship between their antibody levels and prognosis.Renal tissues in 128 patients with membranous nephropathy in the Second Xiangya Hospital of Central South University were collected from February 2015 to August 2017, including 108 patients with primary membranous nephropathy (PMN group) and 20 patients with secondary membranous nephropathy (SMN) (SMN group). Indirect immunofluorescence method was used to detect the expression of PLA2R antigen in kidney tissues,and the glomerular expression of THSD7A antigen was examined by immunohistochemistry and indirect immunofluorescence. The serum levels of anti-PLA2R antibodies and THSD7A antibodies were also detected by ELISA. According to the results of PMN examination,the patients were also divided into a PLA2R-related membranous nephropathy group and a THSD7A-related membranous nephropathy group.The positive rate of PLA2R in the renal tissues in the PMN group was higher than that in the SMN group (78% in the PMN group, 35% in the SMN group,PLA2R and THSD7A are the target antigen of PMN, and the associated autoantibodies are helpful for the differential diagnosis of PMN. The anti-PLA2R antibody levels can reflect the severity of the disease and evaluate the effect of treatment. The incidence of THSD7A membranous nephropathy is low, and monitoring the serum anti-THSD7A antibody levels can assess patients' condition and predict disease outcome.

ESD damage location and diagnosis is a difficult technology for complex IC chips. This study introduces several techniques of ESD damage location, diagnosis and analysis for complex chips, including conventional analysis techniques such as optical microscopy and scanning electron microscopy, as well as advanced analysis techniques such as low light detection, hot spot analysis and magnetic induction imaging analysis. It also introduces the method, process and identification method of IC chip damage diagnosis. Some practical cases show the application of ESD damage location diagnosis technology, which has important guiding significance for the design, manufacture, assembly, application and failure analysis of complex integrated circuits.

Stitching alkynes into bryostatin 3 The bryostatin family of marine natural products has been explored for a wide variety of pharmaceutical applications but remains challenging to source. The general structure comprises a macrocycle that contains three smaller, six-membered rings. Bryostatin 3 is distinguished by the added complexity of a fourth, fused lactone ring. Trost et al. report a convergent synthesis of this complex molecule, taking advantage of alkyne coupling reactions to stitch together three main fragments and asymmetric dihydroxylation and propargylation reactions to set stereochemistry. Science , this issue p. 1007

Cyclobutanones are synthetically versatile compounds that often requires extensive effort to access. Herein, we report a facile synthesis of cyclobutanones based on the C(sp 3 )-H insertion chemistry of oxidatively generated gold carbenes. A range of cyclobutanones was obtained in synthetically useful yields from substrates with minimal structural prefunctionalization. This discovery reveals new synthetic utilities of gold-catalyzed oxidative transformations of alkynones.