An Asymmetric Hydrogenation/N-Alkylation Sequence for a Step-Economical Route to Indolizidines and Quinolizidines.

The direct catalytic asymmetric hydrogenation of pyridines for the synthesis of piperidines remains a challenge. Herein, we report a one-pot asymmetric hydrogenation of pyridines with subsequent N-alkylation using a traceless Brønsted acid activation strategy. Catalyzed by an iridium-BINAP complex, the substrates undergo ketone reduction, cyclization and pyridine hydrogenation in sequence to form indolizidines and quinolizidines. The absolute configuration of the stereocenter of the alcohol is retained and influences the formation of the second stereocenter. Experimental and theoretical mechanistic studies reveal that the chloride anion and certain noncovalent interactions govern the stereoselectivity of the cascade reaction throughout the catalytic process.

Wet-Adhesive Multifunctional Hydrogel with Anti-swelling and a Skin-Seamless Interface for Underwater Electrophysiological Monitoring and Communication.

A stable and seamless adhesion between the human skin and the hydrogel-based electronic skin is necessary for accurate sensing and human health monitoring in aquatic environments. Despite achieving significant progress in this field, it remains a great challenge to design skin-interfaced conductive hydrogels with high electrical conductivity, stablility, and seamless underwater adhesion to skin. Herein, a skin-inspired conductive multifunctional hydrogel is proposed, which has a wet-adhesive/hydrophilic and a non-adhesive/hydrophobic bilayer structure. The hydrogel shows high stretchability (∼2400%) and an ultra-low modulus (4.5 kPa), which facilitate the conformal and seamless attachment of the hydrogel to the skin with reduced motion artifacts. Owing to synergistic physical and chemical interactions, this hydrogel can achieve reliable underwater adhesion and display remarkable underwater adhesion strength (388.1 kPa) to porcine skin. In addition, MXene has been employed to obtain high electrical conductivity, create a route for stable electron transport, and reinforce mechanical properties. The hydrogel also possesses self-healing ability, a low swelling ratio (∼3.8%), biocompatibility, and specific adhesion to biological tissues in water. Facilitated with these advantages, the hydrogel-based electrodes achieve reliable electrophysiological signal detection in both air and wet conditions and demonstrate a higher signal-to-noise ratio (28.3 dB) than that of commercial Ag/AgCl gel electrodes (18.5 dB). Also, the hydrogel can be utilized as a strain sensor with high sensitivity for underwater communication. This multifunctional hydrogel improves the stability of the skin-hydrogel interface in aquatic environments and is expected to be promising for the next-generation bio-integrated electronics.

Broadband yellow-orange light generation based on a step-chirped PPMgLN ridge waveguide.

Yellow-orange lights, valuable in photodynamic therapies, spectroscopy, and optogenetics, are limited by the narrow bandwidth and bulky setup via the conventional Raman or optical parametric oscillation processes. Moreover, flatness in the broad-band spectrum is also important for the aforementioned applications with extended functions. In this paper, by carefully designing grating-periods of a step-chirped PPMgLN ridge waveguide for sum frequency generation (SFG), we report a compact broad-band yellow-orange light with bandwidth of 5.6 nm and an un-reported flatness (<1.5 dB). Correspondingly, the optical conversion efficiency is 232.08%/W, which is the best SFG efficiency for PPMgLN at the yellow-orange region, to the best of our knowledge. The results could also be adopted for other broad-band SFG process toward the vis-infrared region in an integrated structure.

1,2-Diamines as the Amine Sources in Amidation and Rhodium-Catalyzed Asymmetric Reductive Amination Cascade Reactions.

The sturdy chelation of 1,2-diamines and transition-metals would retard or even interrupt the routine catalytic cycles. In the amidation and asymmetric reductive amination (ARA) cascade reactions of diamines and ketoesters, we deployed sets of additives to ensure a smooth transformation catalyzed by the complexes of rhodium and versatile and highly modular phosphoramidite-phosphine ligands. The tunability of the ligands was fully exploited to accommodate various diamines and α-ketoesters for the efficient synthesis of chiral 3,4-dihydroquinoxalinones.

Iridium-catalyzed direct asymmetric reductive amination utilizing primary alkyl amines as the N-sources.

Direct asymmetric reductive amination is one of the most efficient methods for the construction of chiral amines, in which the scope of the applicable amine coupling partners remains a significant challenge. In this study we describe primary alkyl amines effectively serve as the N-sources in direct asymmetric reductive amination catalyzed by the iridium precursor and sterically tunable chiral phosphoramidite ligands. The density functional theory studies of the reaction mechanism imply the alkyl amine substrates serve as a ligand of iridium strengthened by a (N)H-O(P) hydrogen-bonding attraction, and the hydride addition occurs via an outer-sphere transition state, in which the Cl-H H-bonding plays an important role. Through this concise procedure, cinacalcet, tecalcet, fendiline and many other related chiral amines have been synthesized in one single step with high yields and excellent enantioselectivity.

Improving the repair mechanism and miRNA expression profile of tibial defect in rats based on silent information regulator 7 protein analysis of mesenchymal stem cells.

The aim of this study was to verify the role of Silent Information Regulator 7 (SIRT7) in improving the repair mechanism of bone marrow mesenchymal stem cells (BMMSCs) and the expression of microribonucleic acid (miRNA). Human BMMSCs were extracted from patients with femoral fractures, and the proliferation activity of human BMMSCs before and after knockout SIRT7 and the expression levels of bone-related genes and proteins were compared. Thirty-two 8-week-old male Sprague-Dawley (SD) rats were randomly divided into a blank group, a chitosan scaffold group, a control group, and a silence information regulator knockout group 7 (n = 8). In addition to the blank group, the chitosan scaffold, the green fluorescent protein (GFP) transfected stem cell composite chitosan scaffold, and the SIRT7 knockout stem cell composite chitosan scaffold were implanted in the other three groups, respectively. The X-rays and small animal in vivo three-dimensional tomography (Micro-CT) were adopted to quantitatively analyze the volume fraction, the number of trabeculae, and the connection density. Compared with the other three groups, the bone defect was formed more in the medullary mesenchymal stem cell knockout group, and the bone volume fraction, number of trabeculae and connection density were significantly increased (P < 0.05). MiR-98-5p can significantly promote the formation of bone molecules and bone structure in rats (P < 0.05). Human BMMSCs combined with chitosan scaffold can accelerate the repair of tibial defects. MiR-98-5p targeting and regulating bone formation gene (CKIP-1) could significantly improve the process of osteogenesis in rats.

Circ-ATAD1 is overexpressed in osteosarcoma (OS) and suppresses the maturation of miR-154-5p to increase cell invasion and migration.

BACKGROUND: Circ-ATAD1 plays an oncogenic role in gastric cancer. However, its roles in other cancers are unclear. We aimed to analyze the role of circ-ATAD1 in osteosarcoma (OS). METHODS: The expression levels of circ-ATAD1, mature miR-154-5p, and premature miR-154-5p in paired OS and non-tumor tissues from 56 OS patients were determined using RT-qPCR. Nuclear fractionation assay was performed to analyze the subcellular location of circ-ATAD1. The interaction between circ-ATAD1 and premature miR-154-5p was analyzed using RNA pull-down assay. The role of circ-ATAD1 in regulating miR-154-5p maturation was analyzed using RT-qPCR in cells with overexpression. Transwell assays were performed to analyze the roles of circ-ATAD1 and miR-154-5p in regulating OS cell invasion and migration. RESULTS: Circ-ATAD1 was overexpressed in OS compared to non-tumor tissues and was detected in the nuclei of OS cells. Mature miR-154-5p, but not premature miR-154-5p, was downregulated in OS tissues compared to non-tumor tissues and was inversely correlated with circ-ATAD1. In OS cells, circ-ATAD1 overexpression decreased the expression of mature miR-154-5p, but not premature miR-154-5p. Transwell assay analysis showed that circ-ATAD1 overexpression increased cell invasion and migration, and mature miR-154-5p overexpression suppressed these cell behaviors. In addition, circ-ATAD1 overexpression reduced the effects of mature miR-154-5p overexpression on cell behaviors. CONCLUSIONS: Circ-ATAD1 is overexpressed in OS and suppresses miR-154-5p maturation to increase cell invasion and migration.

Involvement of increased expression of chemokine C-C motif chemokine 22 (CCL22)/CC chemokine receptor 4 (CCR4) in the inflammatory injury and cartilage degradation of chondrocytes.

CCL22, which could induce chondrocyte apoptosis, was identified to be overexpressed in damaged cartilage. This study was conducted with the aim of investigating the effects of CCL22 interference on chondrocyte injury. The osteoarthritis model was established by stimulating chondrocytes with LPS. The expressions of CCL22, CCR4, matrix metallopeptidase (MMP) 3, MMP9, MMP13, (a disintegrin and metalloproteinase with thrombospondin-like motifs) ADAMTS-4, collagen II and inflammatory cytokines were measured using quantitative reverse transcription PCR (RT-qPCR) and western blot. Besides, immunoprecipitation (IP) was employed to verify the binding of CCL22 and CCR4. After CCR4 was overexpressed, cell viability was observed using Cell Counting Kit-8 (CCK-8). Additionally, cell apoptosis as well as its related proteins was detected by TUNEL and western blot, respectively. ng What's more, glycosaminoglycan (GAG) level was detected using GAG kits. CCL22 and CCR4 expression increased noticeably in LPS-stimulated ATDC5 chondrocytes. CCL22 inhibition could suppress the expression of CCR4 in LPS-induced ATDC5 cells. Likewise, CCL22 inhibition could revive the activation of LPS-induced ATDC5 cells by regulating CCR4. In addition, CCL22 knockdown alleviated inflammatory response and cell apoptosis through CCR4. Furthermore, the cartilage degradation of ADTC5 cells could be relieved by CCL22 silence via regulating CCR4. CCL22/CCR4 expression was increased in osteoarthritic cartilage injury and participated in the inflammation and cartilage degradation of chondrocytes.

An Iridium Catalytic System Compatible with Inorganic and Organic Nitrogen Sources for Dual Asymmetric Reductive Amination Reactions.

Asymmetric reductive amination (ARA) is one of the most promising methods for the synthesis of chiral amines. Herein we report our efforts on merging two ARA reactions into a single-step transformation. Catalyzed by a complex formed from iridium and a steric hindered phosphoramidite, readily available and inexpensive aromatic ketones initially undergo the first ARA with ammonium acetate to afford primary amines, which serve as the amine sources for the second ARA, and finally provide the enantiopure C2 -symmetric secondary amine products. The developed process competently enables the successive coupling of inorganic and organic nitrogen sources with ketones in the same reaction system. The Brønsted acid additive plays multiple roles in this procedure: it accelerates the formation of imine intermediates, minimizes the inhibitory effect of N-containing species on the iridium catalyst, and reduces the primary amine side products.

1 kHz, 430 mJ, sub-nanosecond MOPA laser system.

We demonstrate a sub-nanosecond MOPA system with a pulse repetition frequency of 1 kHz at 1.06 µm, based on an integrated seed source with pulse energy of 6.2 mJ and two conductively cooled end-pumped Nd:YAG slab gain modules. After a 4-pass amplification stage and a double-pass amplification stage with amplification factors of 12.6 dB and 5.84 dB, respectively, maximum pulse energy of 434 mJ with pulse duration of 691 ps was obtained, corresponding to a peak power of 628 MW. Via adjusting the pump distribution to compensate the static wavefront distortion of the signal laser, the beam quality, at the maximum pulse energy, was optimized to be 2.5 mm·mrad and 2.2 mm·mrad respectively in the vertical and transverse directions. The results benefit a variety of applications including material processing, nonlinear frequency conversion, and lidars.

A hybrid of FEM simulations and generative adversarial networks to classify faults in rotor-bearing systems.

Condition monitoring of rotor-bearing systems using artificial intelligence has great significance to guarantee the reliability and security of mechanical systems. However, in engineering applications, AI model will fail to classify faults with insufficient fault samples owing to complex working condition. A hybrid fault classification approach is presented by combining finite element method (FEM) with generative adversarial networks (GANs) for rotor-bearing systems. Firstly, FEM simulations are employed to calculate simulation fault samples as additional sources of missing fault samples. Secondly, GANs is used to acquire abundant synthetic samples generated from the simulation and measurement samples, which aims to expand fault samples. Finally, the complete fault samples, including simulation, measurement and their corresponding synthetic samples, are utilized as training samples to train typical classifiers, and further to identify unknown faults. High classification accuracies for a rotor-bearing system using different kinds of artificial intelligent (AI) models are obtained, which demonstrates the effective of proposed method. It is noticed that the present idea can be guided to solve insufficient fault samples problem in more complex mechanical system with agreeable fault classification accuracy.

11 W YLF-based intra-cavity pumped Ho laser with near diffraction limited beam quality.

We develop a fluoride-based intra-cavity pumped Ho laser for the first time, where the severe thermal lensing of the intra-cavity pumping mechanism can be compensated by the negative thermal-optical property of the YLiF4 (YLF) host. A maximum output power of 11.3 W (π-pol) at 2062 nm, corresponding to a conversion efficiency of 28.2% from the incident diode laser to the Ho laser, was obtained with a power instability below 0.5% and a near diffraction limited beam quality with M2 of 1.06 and 1.25 in the horizontal and vertical directions, respectively. These are the maximum power and the best beam quality for the reported compact intra-cavity pumped Ho lasers, to the best of our knowledge.

Anisotropic thermal analyses of a high efficiency Tm:YAP slab laser and its intra-cavity pumping for Ho lasers.

We evaluate the thermal effects of a c-cut Tm:YAP slab laser by considering the anisotropic properties of the biaxial YAP crystal. Significant improvements in thermal stress were demonstrated by selecting the crystallographic a-axis, which possesses higher thermal conductivity and thermal expansion, as the direction of the slab thickness. A maximum laser power of 30 W (E//a) at 2 µm was obtained under an incident LD power of 55 W with an optical conversion efficiency of 55.4% and slope efficiency of 61.8% using the a-slab. The slab laser was then used for realizing compact Ho lasers via intra-cavity pumping, resulting in a 0.8 W Ho:YAG laser and a 5.5 W Ho:YAP laser (E//b) at 2.12 µm and 2.13 µm, respectively.

The combination of asymmetric hydrogenation of olefins and direct reductive amination.

Asymmetric hydrogenation (AH) and direct reductive amination (DRA) are both efficient transformations frequently utilized in industry. Here we combine the asymmetric hydrogenation of prochiral olefins and direct reductive amination of aldehydes in one step using hydrogen gas as the common reductant and a rhodium-Segphos complex as the catalyst. With this strategy, the efficiency for the synthesis of the corresponding chiral amino compounds is significantly improved. The practical application of this synthetic approach is demonstrated by the facile synthesis of chiral 3-phenyltetrahydroquinoline and 3-benzylindoline compounds.

A Personalized Diagnosis Method to Detect Faults in a Bearing Based on Acceleration Sensors and an FEM Simulation Driving Support Vector Machine.

Classification of faults in mechanical components using machine learning is a hot topic in the field of science and engineering. Generally, every real-world running mechanical system exhibits personalized vibration behaviors that can be measured with acceleration sensors. However, faulty samples of such systems are difficult to obtain. Therefore, machine learning methods, such as support vector machine (SVM), neural network (NNs), etc., fail to obtain agreeable fault detection results through smart sensors. A personalized diagnosis fault method is proposed to activate the smart sensor networks using finite element method (FEM) simulations. The method includes three steps. Firstly, the cosine similarity updated FEM models with faults are constructed to obtain simulation signals (fault samples). Secondly, every simulation signal is separated into sub-signals to solve the time-domain indexes to generate the faulty training samples. Finally, the measured signals of unknown samples (testing samples) are inserted into the trained SVM to classify faults. The personalized diagnosis method is applied to detect bearing faults of a public bearing dataset. The classification accuracy ratios of six types of faults are 90% and 92.5%, 87.5% and 87.5%, 85%, and 82.5%, respectively. It confirms that the present personalized diagnosis method is effectiveness to detect faults in the absence of fault samples.

Graphene-Based Sensors for Human Health Monitoring.

Since the desire for real-time human health monitoring as well as seamless human-machine interaction is increasing rapidly, plenty of research efforts have been made to investigate wearable sensors and implantable devices in recent years. As a novel 2D material, graphene has aroused a boom in the field of sensor research around the world due to its advantages in mechanical, thermal, and electrical properties. Numerous graphene-based sensors used for human health monitoring have been reported, including wearable sensors, as well as implantable devices, which can realize the real-time measurement of body temperature, heart rate, pulse oxygenation, respiration rate, blood pressure, blood glucose, electrocardiogram signal, electromyogram signal, and electroencephalograph signal, etc. Herein, as a review of the latest graphene-based sensors for health monitoring, their novel structures, sensing mechanisms, technological innovations, components for sensor systems and potential challenges will be discussed and outlined.

Direct 800 nm diode-pumped Holmium laser with broad pump wavelength range and temperature adaptability.

We developed an 808 nm diode laser pumped composite Holmium laser via the integration of Tm-doped and Ho-doped YAG crystals into a single bulk structure. A maximum output power of 1.8 W at 2122 nm with near diffraction-limited beam quality was achieved for an absorbed pump power of approximately 7 W. Given that the pump wavelength is approximately 20 nm away from the absorption peak of the Tm-doped region of the crystal, pump wavelength adaptability of the Tm/Ho composite laser was effectively demonstrated. In this case, a pump range width in excess of 40 nm at approximately 800 nm was predicted by defining the pump spectrum of the gain medium. The temperature adaptability of the Ho laser was demonstrated by varying the cooling temperature from 9 °C to 27 °C. This resulted in Ho laser operation above 1.5 W with a power deviation below 10%. This work presents the experimental results for a compact assessable 2.1 µm laser without pump wavelength and operation temperature restrictions.

Secondary amines as coupling partners in direct catalytic asymmetric reductive amination.

The secondary amine participating asymmetric reductive amination remains an unsolved problem in organic synthesis. Here we show for the first time that secondary amines are capable of effectively serving as N-sources in direct asymmetric reductive amination to afford corresponding tertiary chiral amines with the help of a selected additive set under mild conditions (0-25 °C). The applied chiral phosphoramidite ligands are readily prepared from BINOL and easily modified. Compared with common tertiary chiral amine synthetic methods, this procedure is much more concise and scalable, as exemplified by the facile synthesis of rivastigmine and N-methyl-1-phenylethanamine.

Direct Asymmetric Reductive Amination for the Synthesis of (S)-Rivastigmine.

In this article we demonstrate how asymmetric total synthesis of (S)-rivastigmine has been achieved using direct asymmetric reductive amination as the key transformation in four steps. The route started with readily available and cheap m-hydroxyacetophenone, through esterification, asymmetric reductive amination, N-diphenylmethyl deprotection and reductive amination, to provide the final (S)-rivastigmine in 82% overall yield and 96% enantioselectivity. In the asymmetric reductive amination, catalysed by the iridium⁻phosphoramidite ligand complex and helped by some additives, the readily prepared 3-acetylphenyl ethyl(methyl)carbamate directly reductively coupled with diphenylmethanamine to yield the chiral amine product in 96% ee and 93% yield.

Passively Q-switched solid-state Tm:YAG laser using topological insulator Bi2Te3 as a saturable absorber.

We demonstrated a passively Q-switched solid-state Tm:YAG laser using topological insulator (TI) Bi2Te3 as the saturable absorber (SA) for the first time, to the best of our knowledge. The Q-switched laser pulses were obtained with the minimum pulse width of 382 ns, the maximum pulse energy of 4.8 µJ, the maximum average output power of 272 mW, and a pulse repetition rate of 57.67 kHz. The results indicate that Bi2Te3 can be a promising kind of saturable absorber in the 2 µm wavelength region.