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Abstract: A newly chiral tertiary amine-squaramide has successfully developed and applied into the asymmetric Michael addition of 4-hydroxycoumarin to β,γ-unsaturated α-ketoesters. The catalyst system performed well with a low catalyst loading of 1 mol% under mild reaction conditions. A series of coumarin derivatives were obtained with good yields and enantioselectivities.

Chiral amine-squaramide is a kind of effective hydrogen bond donor bifunctional catalyst to promote many asymmetric transformations. In this paper, novel chiral tertiary amine-squaramide derived from the natural product of the stevioside was developed and applied into the asymmetric Michael addition of acetylacetone to nitroolefins. This asymmetric reaction performed well, and a series of enantiomerically enriched compounds were obtained in high yields (up to 96%) with excellent enantioselectivities (up to 99% ee).

Background The mechanisms underlying the pathogenesis of preeclampsia (PE) remains unclear. Exploring the molecular players in PE progression can provide insights into targeted therapy. Methods The expression levels of circSTAM in placental chorionic tissues of PE patients and normal pregnant women were compared by RT-qPCR. CircSTAM was knocked down by small interfering RNA to investigate its role in migration, invasion and epithelial-mesenchymal transformation (EMT) of trophoblast HTR-8/SVneo cells. The downstream target of circSTAM was predicted using online bioinformatics resources, and their molecular interaction was examined by luciferase reporter assay. Results CircSTAM was upregulated in PE placenta tissues in comparison to normal placental tissues. CircSTAM knockdown significantly enhanced cellular invasion, migration, as well as EMT. Mir-148a-5p was identified as a target of circSTAM to regulate cell migration and invasion. Mir-148a-5p negatively regulated PTEN expression in trophoblast HTR-8 /SVneo cells. Conclusion In summary, circSTAM upregulation in PE trophoblasts promoted the invasion, migration and EMT. CircSTAM may modulate trophoblast phenotype by impinging on mir-148a-5p/PTEN axis. These data provided novel insights into the pathogenesis of PE.

The convenient preparation of N2-unprotected five-membered cyclic guanidines was achieved through a cascade [3 + 2] cycloaddition between organo-cyanamides and α-haloamides under mild conditions in good to excellent yields (up to 99%). The corresponding cyclic guanidines could be easily transformed into hydantoins via hydrolysis.

In this paper, a novel 600 V split-gate VDMOS with the integrated trench MOS barrier Schottky (TMBS) is proposed to reduce the specific gate-drain charge (Q gd,sp) and specific reverse recovery cha...

Mesothelin (MSLN) has been reported to be overexpressed in ovarian cancer and may be an ideal target for immunotherapy. Recent studies have suggested that natural killer (NK) cells may be better chimeric antigen receptor (CAR) drivers because of their favorable innate characteristics, such as directly recognizing and killing tumor cells, resulting in a graft-versus-tumor effect but irresponsible for graft-versus-host disease (GVHD). The therapeutic effects of CAR-engineered NK cells targeting MSLN in ovarian cancer have not been evaluated. In this study, MSLN- and CD19-targeted CAR NK-92 (MSLN- and CD19-CAR NK) cells were constructed. Both MSLN- and CD19-CAR molecules were highly expressed on the surface of NK-92 cells following lentiviral gene transduction. MSLN-CAR NK cells specifically killed MSLN-positive ovarian cancer cells (OVCAR-3 and SK-OV-3), rather than MSLN-negative cells (SK-HEP-1), in vitro. Moreover, compared with parental NK-92 cells and CD19-CAR NK cells, stronger cytokine secretion was detected in MSLN-CAR NK cells cocultured with OVCAR-3 and SK-OV-3. Furthermore, MSLN-CAR NK cells effectively eliminated ovarian cancer cells in both subcutaneous and intraperitoneal tumor models; these cells also significantly prolonged the survival of intraperitoneally tumor-bearing mice. These results demonstrate that MSLN-CAR NK cells have robust specific antitumor activity, both in vitro and in vivo, suggesting that mesothelin could be a potential target for CAR NK cells and could be applied in the treatment of ovarian cancer.

We aimed to investigate the inhibitory effect of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes (hucMSC-Exos) transmitting microRNA-342-5p (miR-342-5p) on the development of preeclampsia (PE) by targeting programmed cell death 4 (PDCD4). The primary hucMSCs were cultured and transfected with miR-342-5p, and the exosomes (Exo) were extracted from the hucMSCs. PE rats were performed with an intraperitoneal injection of L-NAME from days 11 to 19 of gestation, and injection of Exo, Exo-negative control (NC), Exo-miR-342-5p agomir, Exo-miR-342-5p antagomir, and overexpressing PDCD4 (oe-PDCD4) vector into the placenta on the 16th day of pregnancy. HE staining was utilized to observe the pathological changes in placental tissues. TUNEL staining was implemented to evaluate cell apoptosis in placental tissues. Blood pressure and 24-h urinary protein in pregnant rats were measured by a non-invasive rat tail artery blood pressure measurement and protein auto-analyzer. Expressions of miR-342-5p, PDCD4, proinflammatory cytokines (TNF-α and IL-1β), and anti-inflammatory cytokines (IL-10 and TGF-β) were detected by RT-qPCR, and PDCD4 protein expression was determined by Western blot. The interaction between miR-342-5p and PDCD4 was analyzed by luciferase activity assay. MiR-342-5p was downregulated while PDCD4 was upregulated in the placental tissues of PE rats. HucMSC-Exo relieved pathology and suppressed inflammatory response, and apoptosis in the placental tissues, as well as reducing blood pressure and 24-h urinary protein of PE rats. Elevated miR-342-5p enhanced the promoting influence of hucMSC-Exo on PE rats, while inhibited miR-342-5p reversed the functions of hucMSC-Exo on PE rats. miR-342-5p targeted PDCD4. Overexpression of PDCD4 worsened the development of PE in rats. HucMSC-Exo conveying elevated miR-342-5p inhibits the development of PE in a rat model through downregulating PDCD4.

Due to the diversity of design data, the display effect of landscape design is not ideal. Based on the analysis of the requirements of low-carbon landscape design, this paper constructs the hardware condition based on the data acquisition sensor, digital controller, image scanner, data storage device, and power control device and carries out Delaunay triangle netting for the terrain data preprocessed, reduces image shaking by introducing discrete elevation, and improves the image clarity by matching and optimizing the seed points of edge correlation to achieve high-quality visualization of landscape design. The test results show that the design platform can show the design effect completely and clearly.

Printed electronics, which fabricate electrical components and circuits on various substrates by leveraging functional inks and advanced printing technologies, have recently attracted tremendous attention due to their capability of large-scale, high-speed, and cost-effective manufacturing and also their great potential in flexible and wearable devices. To further achieve multifunctional, practical, and commercial applications, various printing technologies toward smarter pattern-design, higher resolution, greater production flexibility, and novel ink formulations toward multi-functionalities and high quality have been insensitively investigated. 2D materials, possessing atomically thin thickness, unique properties and excellent solution-processable ability, hold great potential for high-quality inks. Besides, the great variety of 2D materials ranging from metals, semiconductors to insulators offers great freedom to formulate versatile inks to construct various printed electronics. Here, a detailed review of the progress on 2D material inks formulation and its printed applications has been provided, specifically with an emphasis on emerging printed memristors. Finally, the challenges facing the field and prospects of 2D material inks and printed electronics are discussed.

An efficient preparation of sulfamate-fused 2-aminopyrroles was achieved through an isocyanide-based three-component [1+2+2] annulation of isocyanides, dialkyl acetylenedicarboxylates, and sulfamate-derived cyclic imines in good to excellent yields (up to 99 %). This reaction proceeds smoothly without any activation or modification of substances under neutral and metal-free conditions. The reaction could also be conveniently performed on a gram scale.

A shielded trench split-gate vertical double-diffused metal-oxide-semiconductor field-effect transistor (ST-SG-VDMOS) is proposed, and the analytical model for the main components of specific on-re...

A novel indolium-based fluorescent probe (probe 1) for the recognition and detection of hypochlorite (OCl−) has been explored via a double oxidation reaction mechanism. Probe 1 exhibited excellent selectivity and sensitivity for OCl− over other analytes, and with a detection limit of 0.11 μM. Meanwhile, probe 1 showed fast response toward OCl− in less than 3 min with obvious changes in color, which could be observed by naked eye. Moreover, fluorescence imaging experiments by using Eca109 cells were performed utilizing the new probe, demonstrating its practical applications in living cells.

Modified potato starch with slower digestion may aid the development of new starch derivatives with improved nutritional values, and strategies to increase nutritional fractions such as resistant starch (RS) are desired. In this study, a correspondence between starch structure and enzymatic resistance was provided based on the efficient branching enzyme AqGBE, and modified starches with different amylose content (Control, 100%; PS1, 90%; PS2, 72%; PS3, 32%; PS4, 18%) were prepared. Through SEM observation, NMR and X-ray diffraction analyses, we identified that an increased proportion of α-1,6-linked branches in potato starch changes its state of granule into large pieces with crystallinity. Molecular weight and chain-length distribution analysis showed a decrease of molecular weight (from 1.1 × 106 to 1.1 × 105 g/mol) without an obvious change of chain-length distribution in PS1, while PS2-4 exhibited an increased proportion of DP 6-12 with a stable molecular weight distribution, indicating a distinct model of structural modification by AqGBE. The enhancement of peak viscosity was related to increased hydrophobic interactions and pieces state of PS1, while the contents of SDS and RS in PS1 increased by 37.7 and 49.4%, respectively. Our result provides an alternative way to increase the RS content of potato starch by branching modification.

The application of Chimeric antigen receptor (CAR) T cells in solid tumors is hindered by lack of tumor specific targets and inefficient T cell infiltration in tumor. It has been postulated that AXL may be an ideal immunotherapy target for non-small-cell lung cancer (NSCLC). Here, we screened 208 non-tumor samples from 22 types of human organs or tissues and 90 tumor samples from NSCLC patients by immunohistochemistry or Western Blotting and identified that AXL was rarely expressed in normal tissues but highly expressed in 69% NSCLC samples, suggesting AXL is an ideal target for CAR T cell therapy for lung cancer. We generated low-, mediate-, high-affinity AXL-CARs and evaluated their killing effect on NSCLC. Our data demonstrated antitumor effects of AXL-CAR T cell therapy for various NSCLC models both in vitro and in vivo. AXL-CAR T cells alone exerted strong antitumor effect in subcutaneous lung cancer cell derived xenograft (CDX), pulmonary metastases CDX, and intraperitoneal CDX models. Intraperitoneal delivery of CAR T cells resulted in superior tumor killing effects compared with systemic infusions for the intraperitoneal CDX tumor models. AXL-CAR T combined with microwave ablation (MWA) or EGFR-TKI resulted in enhanced killing effect and CAR-T cell infiltration in vivo. Together, our current study suggests that systemic or regional infusion of AXL-CAR T cell alone or combination with other therapies might have potential translatable value for the treatment of NSCLC in clinical situation.

A highly efficient domino aza-MIRC (Michael Induced Ring Closure) reaction between barbiturate-derived alkenes and N-alkoxy α-haloamides has been achieved in moderate to excellent yields. This reaction proceeds smoothly under mild conditions via a domino aza-Michael addition/intramolecular SN2 sequence, providing a practical tool in the synthesis of bioactive molecules spirobarbiturate-3-pyrrolidinones.

Nutraceuticals containing modified starch with increased content of slowly-digestible starch (SDS) may reduce the prevalence of obesity, diabetes and cardiovascular diseases due to its slow digestion rate. Enzymatic methods for the preparation of modified starch have attracted increasing attention because of their low environmental impact, safety and specificity. In this study, the efficient glucan branching enzyme McGBE from Microvirga sp. MC18 was identified, and its relevant properties as well as its potential for industrial starch modification were evaluated. The purified McGBE exhibited the highest specificity for potato starch, with a maximal specific activity of 791.21 U/mg. A time-dependent increase in the content of α-1,6 linkages from 3.0 to 6.0% was observed in McGBE-modified potato starch. The proportion of shorter chains (degree of polymerization, DP 13) increased from 29.2 to 63.29% after McGBE treatment, accompanied by a reduction of the medium length chains (DP 13-24) from 52.30 to 35.99% and longer chains (DP 25) from 18.51 to 0.72%. The reduction of the storage modulus (G') and retrogradation enthalpy (ΔHr) of potato starch with increasing treatment time demonstrated that McGBE could inhibit the short- and long-term retrogradation of starch. Under the optimal conditions, the SDS content of McGBE-modified potato starch increased by 65.8% compared to native potato starch. These results suggest that McGBE has great application potential for the preparation of modified starch with higher SDS content that is resistant to retrogradation.

Cathelicidin-related antimicrobial peptide (CRAMP) has been reported to have positive immune-modulatory and anti-inflammatory effects. However, the effect of recombinant CRAMP-encoding Lactobacillus plantarum on experimental colitis is unknown. In this study, 4 strains of CRAMP-encoding L. plantarum FCQHC24 were constructed using genetic engineering. They were administered orally to mice for 4 consecutive days after experimental colitis was induced using 3% dextran sodium sulfate (DSS). Disease severity was determined. The levels of colonic inflammatory cytokines and CRAMP and activation of transcription factor nuclear factor-κB (NF-κB) were analyzed. The 4 engineered CRAMP-encoding L. plantarum strains significantly increased the colonic CRAMP production, especially the strains containing the Usp45 signal peptide, accompanied by reduced colon shortening and body weight (bw) loss. In addition, treatment with the engineered probiotics decreased the levels of colonic pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) and increased the level of colonic anti-inflammatory cytokine IL-10 in DSS-induced experimental colitis. The engineered probiotics suppressed DSS-induced phosphorylation and activation of colonic p38, extracellular signal-regulated kinase 1/2, and NF-κB. Taken together, this study showed that CRAMP-encoding L. plantarum FCQHC24 had the therapeutic potential for colitis by modulating colonic CRAMP production.

An efficient potassium hydroxide-catalyzed alkynylation of heteroaromatic N-oxides under transition-metal-free conditions with the assistance of visible-light has been developed. Various C2-alkynylheterocycles were obtained in up to 92% yield with good functional group tolerance. This new method is operational simple, highly efficient, atom economic, and environmental friendly.

Structural modification of starch using efficient α-amylases to improve its properties is an established method in the starch industry. In our previous research, the novel maltogenic α-amylase CoMA that catalyzes multi-molecular reactions has been identified. In this study, the impact of CoMA on the structure and retrogradation properties of potato starch was evaluated. CoMA cleaves internal starch chains to change the proportion of amylose and amylopectin in starch. Following treatment, visible pores and microporous on the surface of starch granules were observed from SEM analysis. CoMA modification led to increased insoluble blue complex formation and hydrolysis to shorten the outer chains, which was found to reduce the development rate of starch according to network interactions from the dynamic rheological analysis. Furthermore, maltose accumulation with water competition was also deduced to be involved in the inhibition of retrogradation. Its activities in the cleavage of internal starch granules, shortening of outer chains of starch, and maltose formation make CoMA a powerful agent for the inhibition of starch retrogradation with a very low effective dose of 0.5 mg/kg, which may find potential applications in the starch processing industry.

The influences of P-pillar and trench technology in VDMOS have been studied by the comparison of five 600 V VDMOS structures, which contain the conventional VDMOS (C-VDMOS), split-gate VDMOS with one floating P-pillar in the middle (SG-VDMOS-P1), split-gate VDMOS with two P-pillars on the each side (SG-VDMOS-P2), split-gate VDMOS with a P-pillar under the trench (SG-VDMOS-TP1) and SG-VDMOS-P2 with a central trench (SG-VDMOS-TP2). The breakdown voltages (BV) and on-resistances $(R_{on})$ of five structures are simulated by the TCAD. The simulation results are given in this paper.

Essential proteins are those necessary for the survival or reproduction of species and discovering such essential proteins is fundamental for understanding the minimal requirements for cellular life, which is also meaningful to the disease study and drug design. With the development of high-throughput techniques, a large number of Protein-Protein Interactions (PPIs) can be used to identify essential proteins at the network level. Up to now, though a series of network-based computational methods have been proposed, it is still a challenge to improve the prediction precision as the high false positives in PPI networks. In this paper, we propose a new method GOS to identify essential proteins by integrating the Gene expressions, Orthology, and Subcellular localization information. The gene expressions and subcellular localization information are used to determine whether a neighbor in the PPI network is reliable. Only reliable neighbors are considered when we analyze the topological characteristics of a protein in a PPI network. We also analyze the orthologous attributes of each protein to reflect its conservative features, and use a random walk model to integrate a protein's topological characteristics and its orthology. The experimental results on the yeast PPI network show that the proposed method GOS outperforms the ten existing methods DC, BC, CC, SC, EC, IC, NC, PeC, ION, and CSC.

The upregulation of homeobox-B7 (HOXB7) in cancers has been reported. However, its role in oral cancer progression remains to be investigated. In current study, our data revealed that reconstitution of HOXB7 expression by transient transfection resulted in increased cell growth, migration and invasion in vitro. In addition, apoptosis and clonogenic assay data showed that overexpression of HOXB7 decreased the sensitivity of oral cancer cells to vincristine-induced apoptosis of HSC-4 and KB/VCR cells. Furthermore, overexpression of HOXB7 promoted oral cancer cells' migration and invasion through activation of TGFβ2/SMAD3 signaling pathway. Moreover, forced expression of HOXB7 increased Bcl-2 to Bax ratio, which would promote cell survival and induce drug and radiotherapy resistance. Altogether, our findings support the role of HOXB7 in the progression of oral cancer. Therefore, HOXB7 potentially can be a therapeutic target for oral cancer.

A facile and efficient protocol for palladium-catalyzed C8-selective acylation of quinoline N-oxides with α-oxocarboxylic acids has been developed. In this approach, N-oxide was utilized as a stepping stone for the remote C-H functionalization. The reactions proceeded efficiently under mild reaction conditions with excellent regioselectivity and broad functional group tolerance.

A novel ratiometric fluorescence probe (M1) for hypochlorite (ClO−) based on a mechanism of Fluorescent Resonance Energy Transfer (FRET) has been constructed. Probe M1 can be regarded as a difunctional probe for ClO− and Hg2+. Probe M1 exhibited good specificity and sensitivity towards ClO− over other related analytes as along with low detection limit (13.6 nM). Furthermore, it has been successfully used in living Eca109 cells for fluorescence imaging hypochlorite.

A novel indolium-based fluorescent probe (probe 1) for the recognition and detection of hypochlorite (OCl

With a fixed breakdown voltage of the power MOSFET, the on-state resistance is always optimized by introducing a heavy doping concentration into the JFET region. This heavy doping concentration can be accomplished by ion implantation and following corresponding thermal steps. The implanted atoms distribute in a related range of depth. This phenomenon will make compensation of the p-type impurities in base regions. Thus the threshold voltage and blocking capability of the device will be different from the intended targets. In this paper, analytical and simulation study are made to analyze the impact from JFET region doping on the characteristics of power MOSFETs. Process parameters like implantation dosage and drive-in temperature are the key factors which have important influence on the final device characteristics. With fixed drive-in temperature and time, bigger implantation dosage will lead a bigger compensation of the p-type atoms in base regions. Then the threshold voltage and the breakdown voltage will be smaller. With a fixed implantation dosage, the higher drive-in temperature will make the atoms diffuse deeper. If the junction depth of the JFET region doping exceeds the junction depth of the base regions, the breakdown voltage will decrease obviously. So the process parameters for JFET region doping should be adjusted carefully.

The failure models of 700 V VDMOSFET have been established according to the test results. The maximum theoretical breakdown voltage of 520 V and the simulation of the failure models are in agreement with the failure analysis and the test result. It's believed that the failure is induced by the large space between the junctions due to the inappropriate gate-pad area layout design. Two schemes are given to construct a large junction under the gate-pad to solve the failure problem in this paper. The first scheme is that the total gate-pad area is covered by the GR mask usually used to form the deep field limiting rings (FLRs) to support high voltage. In the second scheme, the GR mask is instead by the AA mask resulting in a shallow junction with a modified length of polysilicon-gate-bus. The validity of two schemes has been proved by the simulation. Only the first scheme has been implemented because of the second tape-out cost, and the final test breakdown voltage is about 710 V almost satisfying the design target.

“In-situ” error detection and correction (EDAC) techniques have been proposed to reduce PVTA margins and improve energy efficiency. However, previous EDAC works incur large design complexity and overhead. In this paper, we propose a light-weight energy-efficient latch transition sensor(LTS) that adds only 12 transistors to a conventional latch. It uses a two-way monitor that senses data transitions within detection window to indicate timing errors. It has low hardware overhead and increases energy efficiency. LTS is implemented in a commercial processor at SMIC 40nm process with a energy saving of 34.55%, while incurring 9.33% system area overhead compared to a baseline design. At 0.6v, the LTS processor gains 6.89% performance increasing at fixed voltage, 2%∼7% energy saving at fixed throughput and 1%∼3% less area overhead than other error-resilient processors using previous EDAC techniques.

In this paper, we propose to add a BOXID at conventional Umosfet device in its drift region that shows an improvement in the breakdown performance as compared to the conventional trench device due to a reduction in the vertical electric field, and through the TCAD software to optimally adjust the position and thickness of the BOXID in the device. The simulation results show that in the two device on resistance is very similar, the Umosfet voltage of the device is increased from 33 V to 59 V, and the performance is stable.

The thermal oxidizing process used to manufacture UMOS causes the interface of SiO 2 /Si existing a great deal of interface charge, which influenced the electrical properties of device. The SWB platform is used to investigate the influence of SiO 2 /Si interface charge on the electrical properties of UMOS. The simulation result shows that the drain current increases with the increase of interface charge, and the breakdown voltage, threshold voltage and on-resistance decrease with the increase of interface charge, which is consistent with theoretical analysis. The influence of interface charge on the electrical properties of UMOS is negligible when the surface charge density is lower than 2.5e11 cm∼2, on the contrary, it will make the drain current increase and breakdown voltage drop sharply and even make a failure of the device.