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Herein, a series of chiral δ-lactam frameworks have been synthesized and catalyzed by chiral phosphoric acid (CPA) utilizing two kinds of open-chain aza-dienes and azlactones derived from amino acids. This powerful [4 + 2] annulation produces a broad substrate scope with functional group tolerance in yield up to 97% with up to 98:2 er. Moreover, a facile scale-up and straightforward conversion to diversely substituted products verify the synthetic utility of this method featuring good compatibility and high efficiency.

The optimal chemotherapy regimen pre-transplantation for adult T-cell acute lymphoblastic leukemia (T-ALL) patients remains unknown. Here, we compared the transplant outcomes in 127 subjects receiving pediatric- (N= 57) or adult-type (N= 70) regimens pre-transplant. The corresponding 3-year cumulative incidences of relapse (CIR) was 7% (95% CI: 3–11%) and 29% (95% CI: 23–35%; P= 0.02), leukemia-free survivals (LFS) was 86% (95% CI: 81–91%) and 57% (95% CI: 51–63%; P= 0.003), overall survivals (OS) was 88% (95% CI: 84–92%) and 58% (95% CI: 52–64%; P= 0.002), the 1-year NRM was 4% (95% CI: 1–7%) and 9% (95% CI: 4–14%; P= 0.40). Multivariate analysis showed that pediatric-type regimen was associated with lower CIR (Hazard Ratio [HR] = 0.31 [95% CI: 0.09–1.00]; P= 0.05), better LFS (HR = 0.34 [95% CI: 0.15–0.78]; P= 0.01) and OS (HR = 0.30 [95% CI: 0.13–0.72]; P= 0.01). Our results suggested that adult T-ALL patients undergoing allo-HSCT might benefit from pediatric-type chemotherapy.

ABSTRACTAlthough the majority of the population will be protected due to the advent and widespread use of the HPV vaccine, the treatment of cervical cancer for all causes, including HPV-negative cervical cancer, is still worthy of further research. The focal point of this study was Canadine’s inhibition of epithelial-mesenchymal transformation (EMT) in cervical cancer. Immunoblotting, wound healing and tumor invasion experiments showed that low concentration of Canadine could inhibit the EMT process, proliferation and migration of HT-3 cells (HPV-negative cell line). Combined with GEO database, it was found that the expression levels of several genes highly expressed in cervical tumor tissues could be inhibited by Canadine, especially MAGEA3. Further experiments confirmed that the inhibition of Canadine on MAGEA3 protein increased with time. The small interference and overexpression plasmid of MAGEA3 were designed and verified. In HT-3 cells, when MAGEA3 levels were directly decreased, mesenchymal phenotypic markers were decreased and epithelial phenotypic markers were increased. The opposite result was obtained by overexpression of MAGEA3. In addition, the inhibition of EMT due to the reduction of endogenous MAGEA3 by Canadine was also offset by the overexpression of exogenous MAGEA3. The study concludes that Canadine inhibits EMT of cervical cancer by inhibiting MAGEA3.

The tendon-to-bone healing after trauma is usually slow and weak, and the repair site is easily disrupted during early mobilization exercise. bFGF and VEGFA gene therapy may hold promise in augmenting the tendon-to-bone healing process through enhancing cell proliferation and angiogenesis. This study is conducted to determine the effects of nanoparticle-mediated co-delivery of bFGF and VEGFA genes to the tendon-to-bone repair interface on the healing strength and biological responses in a chicken model. The PLGA nanoparticle/pEGFP-bFGF + pEGFP-VEGFA plasmid complexes were prepared and were characterized in vitroand in vivo. The nanoparticle/plasmid complexes can effectively transfer bFGF and VEGFA genes to the tendon-to-bone interface. Nanoparticle-mediated co-delivery of bFGF and VEGFA genes significantly improved the tendon-to-bone healing in terms of healing strengths and histology in a chicken flexor tendon repair model. Our results suggest a new biological approach to accelerate the tendon-to-bone healing.

How to accelerate tendon healing remains a clinical challenge. In this study, a suture carrying nanoparticle/pEGFP-basic fibroblast growth factor (bFGF) and pEGFP-vascular endothelial growth factor A (VEGFA) complexes was developed to transfer the growth factor genes into injured tendon tissues to promote healing. Polydopamine-modified sutures can uniformly and tightly absorb nanoparticle/plasmid complexes. After tendon tissues were sutured, the nanoparticle/plasmid complexes still existed on the suture surface. Further, we found that the nanoparticle/plasmid complexes delivered into tendon tissues could diffuse from sutures to tendon tissues and effectively transfect genes into tendon cells, significantly increasing the expression of growth factors in tendon tissues. Finally, biomechanical tests showed that nanoparticle/pEGFP-bFGF and pEGFP-VEGFA complex-coated sutures could significantly increase the ultimate strengths of repaired tendons, especially at 4 weeks after operation. Two kinds of nanoparticle/plasmid complex-coated sutures significantly increased flexor tendon healing strength by 3.7 times for Ethilon and 5.8 times for PDS II, respectively, compared with the corresponding unmodified sutures. In the flexor tendon injury model, at 6 weeks after surgery, compared with the control suture, the nanoparticle/plasmid complex-coated sutures can significantly increase the gliding excursions of the tendon and inhibit the formation of adhesion. These results indicate that this nanoparticle/plasmid complex-coated suture is a promising tool for the treatment of injured tendons.

Preoperative fasting, water deprivation, and intraoperative fluid loss and redistribution result in hypovolemia in patients undergoing surgery. Some findings have indicated that the superior vena cava (SVC) diameter and variation, as determined by transesophageal echocardiography during surgery, do not reflect central venous pressure effectively. This study aimed to compare and correlate the SVC diameter and variation with the stroke volume variation for predicting fluid responsiveness in patients undergoing invasive positive pressure ventilation. Thirty‐six patients scheduled for elective gastrointestinal surgery under general anesthesia with invasive positive pressure ventilation were included in this study. After anesthesia induction, the stroke volume variation, SVC diameter, mean arterial pressure, central venous pressure, and pulse were recorded, and measurements after fluid challenge were recorded as well. The SVC variation was calculated before and after the fluid challenge. After the fluid challenge, the SVC diameter markedly increased, whereas the SVC variation and stroke volume variation significantly decreased (P< .05). The optimal cutoff value for the SVC variation was 21.1%, and the area under the curve (AUC) from a receiver operating characteristic curve analysis was 0.849. The optimal cutoff value for the minimal SVC diameter was 1.135 cm, and that AUC was 0.929. In addition, the optimal cutoff value for the maximal SVC diameter was 1.480 cm, and the AUC was 0.862. The minimal SVC diameter may be an effective indicator for predicting fluid responsiveness in patients undergoing invasive positive pressure ventilation.

An organic chemistry experiment designed for senior undergraduates focuses on bifunctional catalysis, a critical yet often omitted topic at the undergraduate level, but essential for advanced studies in chemistry. By utilization of a tertiary amine-thiourea catalyst in the asymmetric Michael addition reaction, the experiment showcases the superiority of bifunctional catalysis over traditional monofunctional approaches. Comprehensive training in designing control experiments, performing flash chromatography, and analyzing results with NMR and HPLC techniques equip students with modern synthetic skill sets. This experiment features easy operation and a relatively short time (4.5 h, including 2–2.5 h reaction time). More importantly, it bridges the educational gap in understanding advanced catalytic mechanisms and techniques in organic chemistry.

Here, we present a versatile, silver-catalyzed multi-auto-tandem reaction involving enamines, alkynals, and nucleophiles, utilizing the highly reactive intermediate azafulvenium. This method allows for flexible and switchable regiodivergent reactions through either intermolecular or intramolecular nucleophilic attacks, which can be controlled by adjusting the catalytic conditions. A range of site-specific functionalized or polycyclic fused pyrrole products were efficiently produced with a high level of chemocontrol.

By employing an electrical micro-titration system, in which a capacitively coupled contactless conductivity detector is used to monitor the reaction process in real time, ciprofloxacin hydrochloride in tablet samples is determined. Because the reaction solutions are isolated from the working electrodes, it shows significant simplicity and cost-effectiveness, by eliminating the requirements for detector exchange/renewal between measurements, and by involving no auxiliary chemicals.

With the growing attention drawn to the electrical substation electromagnetic environmental problem, the application of material with electromagnetic shielding effect gains more and more popularity. This work evaluated the electromagnetic shielding effect of aluminum foam in 10 kV Xifaxian transformer dado and three electrical substations, a 66 kV Niluo substation, a 220 kV Hexi substation and a 500 kV Keerqin substation. 304L stainless steel and its composite material were also used as a comparison. By comparing with the environmental data, it showed that the power frequency electric field intensity next to the transformer of 500 kV Keerqin substation was slightly higher than the national standard, whereas the other power frequency electric field and magnetic induction intensities were lower than the limit values. The power frequency electric field and magnetic induction intensities attenuated with the increase of measuring distance from enclosing wall. 304L stainless steel, aluminum foam and their composite materials all had certain electromagnetic shielding effect. Aluminum foam and composite materials had almost the same shielding effect for power frequency electric field, which was slightly better than 304L stainless steel. Unlike the electric shielding effect, the magnetic shielding effect of aluminum foam was significantly superior to that of the 304L stainless steel. Meanwhile, their composite material had the best one.

CH3NH3PbI3 thin film was deposited by a dual-source evaporation system under high vacuum (∼10−4 Pa). The crystallographic phase was analyzed by X-ray diffraction and confirmed as the perovskite structure. The optical properties of the thin film have been investigated in the spectral range 300-1800 nm. The analysis of the absorption coefficient () reveals direct allowed transition with corresponding energy 1.58 eV. The surface morphology of the film was characterized by atomic force microscopy (AFM). The observed features exhibited by CH3NH3PbI3 give a vital chance to explore its application for various optoelectronic devices. To see its other potential utility, Al/CH3NH3PbI3 /ITO Schottky diodes were fabricated. Based on the analyzing the I-V measurement for the Al/CH3NH3PbI3/ ITO device, the basic device parameters such as barrier height and ideality factor were determined. At the low-voltage region, the current conduction in the device is ohmic type. The charge transport phenomenon appears to be space charge limited current (SCLC) at higher-voltage regions.

In this article, a three-dimensional time-dependent model describing the evolution of single pore during the solid/gas eutectic unidirectional solidification process (also called gasar process) was established. The mass transfer, bubble nucleation, pore growth and interruption were all considered in this model. The pore structure of lotus-type porous copper and aluminum were simulated under different solidification velocities. The results indicate that: coupled growth of both solid and gas phases can be achieved in a proper range of solidification velocities. The solidification velocity for Cu-H2 system is dozens of that for Al-H2 system when the pore diameter is similar to each other. The differences of the solute distribution coefficient (k0), diffusion coefficient (DL) and the constant of solubility of hydrogen (ξ(Tm)) in the melt are regarded as the main reasons of the big discrepancy of solidification velocity between Cu-H2 and Al-H2 systems.

Based on the solid–gas eutectic unidirectional solidification technique and the principle of unidirectional solidification of single-phase alloy, a new method for evaluating the diffusion coefficient of hydrogen in liquid metals was proposed. Taking Cu–H2system for example, the influences of argon partial pressure and superheat degree of melt on the diffusion coefficient of hydrogen in liquid metal were studied and the predicted values were similar to each other. The obtained temperature-dependent equation for diffusion coefficient of hydrogen in liquid copper is comparable with experimental data in literature, which validates the effectiveness of this method. The temperature-dependent equations for diffusion coefficient of hydrogen in liquid Mg, Si and Cu–34.6%Mn alloy were also evaluated by this method, along with the values at the melting point of each metal and alloy.

Lotus-type porous silicon with elongated pores was fabricated by unidirectional solidification under pressurized hydrogen. Porosity, pore diameter, and pore length can be adjusted by changing solidification speed and hydrogen pressure. The porosity of the ingot is nearly constant under different solidification speeds, but decreases with the increase of hydrogen pressure. The overall porosities of ingots fabricated at different hydrogen pressures were evaluated through a theoretical model. Findings are in good agreement with experimental values. The average pore diameter and pore length increase simultaneously while the average pore aspect ratio changes slightly with the decreases of solidification speed and hydrogen pressure. The average pore length is raised from 7 to 24 mm and the pore aspect ratio is raised from 8 to 20 respectively with the average pore diameter promoted by about 0.3 mm through improving the superheat degree of the melt from 200 to 300 K.

In this work, a new method to determine the interference grade of the central film is put forward. The interference figure is generated on a steel ball and a glass disc with a green monochromatic two-beam interferometry. With gradually increasing the rotational speed of the glass disc, the corresponding interference intensities of the central contact area are continually collected and sent to the computer. With these data, the periodical curve of the central interference grey value with the sliding speed has been drawn. Then, the curve is compared with the theoretical result so that the central interference grade of each figure can be determined. It has been found that while the sliding speed varies from 0.09 m/s to 0.21 m/s, the central interference grade of the interference figure is the first under the working conditions of the present paper. As the sliding speed increases between 0.21 m/s and 0.4 m/s, the second grade of the central interference figure is achieved. As the central interference grade has been known, the film thickness and the film shape can be easily determined by the interference picture of the EHL film and the relative optical intensity principle.

Lotus-type porous silicon is a promising micro-channel heat sink material in cooling of high powered electronic devices. Lotus-type porous silicon with elongated pores has been successfully fabricated by unidirectional solidification at different velocities. The average pore diameter and inter-pore spacing all increase whether along the height direction of the ingot or with increasing the thickness of graphite sheet (lower solidification velocity). The calculated porosity is in good agreement with the experimental results which almost keep as constant at different solidification velocities. The penetration ratio or the pore length increases with decreasing solidification velocity. The bigger pores are more likely to grow longer than smaller ones. In addition, the microstructure observation shows that the pores mostly distribute at the grain boundaries.

Ultrathin MgB2 film is essential for the fabrication of MgB2 superconducting single photon detectors (SSPDs). In this paper, we prepared 20nm and 10nm MgB2 film using ex-situ annealing of Mg-B multilayer method. The precursor films were prepared by electron beam evaporation. A flowing Mg vapour and H2 was introduced in the annealing process to keep MgB2 thin film thermodynamically stable. The annealing temperature was between 680 and 740 and annealing time was 1-10min. 20nm MgB2 films on MgO(111) substrates had the critical temperature (Tc) of 32.2K. The films grew along c-axes direction. As the substrate changed to SiC(001) and Al2O3(001), Tc decreased to 30.3K and 10.2K respectively. For 10nm MgB2 film on SiC(001) substrate, Tc was 24.2K. The self-field critical current density for 10nm and 20nm film on SiC(001) substrate was 2.1×106A/cm2 and 2.3×106A/cm2, respectively. AFM image showed that the film had a flat surface with mean roughness of 0.899nm for 10nm MgB2 film.

In the present paper, a new method for measuring elastohydrodynamic lubrication (EHL) pressure in line contact is proposed, which is based on the photoelastic technique. The pressure distribution of EHL film and the inner stresses in the friction pairs are fundamental issues to carry out EHL research. The film thickness, pressure and temperature have been successfully obtained with solving the basic equations such as Reynolds equation and energy equation simultaneously or separately, with numerical model of EHL problem. The film thickness can be also measured with the optical interference technique. However, the pressure measurement is still a problem which has not been well solved yet, so as the inner stresses inside the friction pairs. With the experimental mechanics, the photoelastic technique is a possible method to be used for measuring the pressure distribution of EHL film and inner friction pair in the line contact. Therefore, A flat plastic disk and a steel roller compose the frictional pairs of the photoelastic pressure measuring rig with combining the monochromatic LED light source, polarizer CCD camera and stereomicroscope to form the whole pressure measuring system of the line contact EHL. The experimental results with the rig display the typical features of EHL pressure. This shows that the method is feasible to be used for measuring the pressure of EHL film and the inner stresses of the friction pairs in the line contact.

Background: Long noncoding enhancer RNAs (lnc-eRNAs) are a subset of stable eRNAs identified from annotated lncRNAs. They might act as enhancer activity-related therapeutic targets in cancer. However, the underlying mechanism of epigenetic activation and their function in cancer initiation and progression remain largely unknown. Results: We identify a set of lncRNAs as lnc-eRNAs according to the epigenetic signatures of enhancers. We show that these lnc-eRNAs are broadly activated in MLL-rearranged leukemia (MLLleukemia), an aggressive leukemia caused by a chromosomal translocation, through a mechanism by which the HOXA cluster initiates enhancer activity, and the epigenetic reader BRD4 cooperates with the coregulator MLL fusion oncoprotein to induce transcriptional activation. To demonstrate the functional roles of lnc-eRNAs, two newly identified lnc-eRNAs transcribed from the SEELA eRNA cluster (SEELA), SEELA1 and SEELA2, are chosen for further studies. The results show that SEELA mediated cis-activated transcription of the nearby oncogene Serine incorporate 2(SERINC2) by directly binding to the K31 amino acid (aa) of histone H4. Chromatin-bound SEELA strengthens the interaction between chromatin and histone modifiers to promote histone recognition and oncogene transcription. Further studies show that the SEELA-SERINC2 axis regulated aspects of cancer metabolism, such as sphingolipid synthesis, to affect leukemia progression. Conclusions: This study shows that lnc-eRNAs are epigenetically activated by cancer-initiating oncoproteins and uncovers a cis-activating mechanism of oncogene transcription control based on lnc-eRNA-mediated epigenetic regulation of enhancer activity, providing insights into the critical roles of lnc-eRNAs in cancer initiation and progression.