Dexmedetomidine Protects Against Kidney Fibrosis in Diabetic Mice by Targeting miR-101-3p-Mediated EndMT.

Objective: Our main purpose is to explore the effect and mechanism of Dexmedetomidine (DEX)  in diabetic nephropathy fibrosis. Methods: Diabetic model was established by intraperitoneal injection of streptozotocin (STZ) treated CD-1 mice and high glucose cultured human dermal microvascular endothelial cells (HMVECs). Immunofluorescence was used to detect renal endothelial-mesenchymal transition (EndMT); Hematoxylin and Eosin (HE) staining and Masson's Trichrome Staining (MTS) was used to analyze renal fibrosis; CCK-8 was used to evaluate cell viability; Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression of miR-101-3p; Western blots were utilized to judge the protein expression levels of EndMT, extracellular matrix and TGF-ß1/Smad3 signal pathway. Results: In this study, we first found that the protective effect of DEX on DN was related to EndMT. DEX alleviated kidney fibrosis by inhibiting EndMT in diabetic CD-1 mice. DEX could also inhibit high glucose-induced HMVECs EndMT. Then, we confirmed that miR-101-3p was the regulatory target of DEX. The expression of miR-101-3p was decreased in diabetic CD-1 mice and high glucose-induced HMVECs. After DEX treatment, the miR-101-3p increased, and the inhibition of miR-101-3p could counteract the protective effect of DEX and aggravate the EndMT. Finally, we found that the TGF- ß1/Smad3 signal pathway was involved in the protective effect of DEX on DN. DEX inhibited the activation of TGF-ß1/Smad3 signal pathway. On the contrary, inhibiting miR-101-3p promoted the expression of TGF-ß1/Smad3. Conclusion: DEX protects kidney fibrosis in diabetic mice by targeting miR-101-3p-mediated EndMT.

A 13-Bit, 12-ps Resolution Vernier Time-to-Digital Converter Based on Dual Delay-Rings for SPAD Image Sensor.

A three-dimensional (3D) image sensor based on Single-Photon Avalanche Diode (SPAD) requires a time-to-digital converter (TDC) with a wide dynamic range and fine resolution for precise depth calculation. In this paper, we propose a novel high-performance TDC for a SPAD image sensor. In our design, we first present a pulse-width self-restricted (PWSR) delay element that is capable of providing a steady delay to improve the time precision. Meanwhile, we employ the proposed PWSR delay element to construct a pair of 16-stages vernier delay-rings to effectively enlarge the dynamic range. Moreover, we propose a compact and fast arbiter using a fully symmetric topology to enhance the robustness of the TDC. To validate the performance of the proposed TDC, a prototype 13-bit TDC has been fabricated in the standard 0.18-µm complementary metal-oxide-semiconductor (CMOS) process. The core area is about 200 µm × 180 µm and the total power consumption is nearly 1.6 mW. The proposed TDC achieves a dynamic range of 92.1 ns and a time precision of 11.25 ps. The measured worst integral nonlinearity (INL) and differential nonlinearity (DNL) are respectively 0.65 least-significant-bit (LSB) and 0.38 LSB, and both of them are less than 1 LSB. The experimental results indicate that the proposed TDC is suitable for SPAD-based 3D imaging applications.

Knockdown of LncRNA-H19 Ameliorates Kidney Fibrosis in Diabetic Mice by Suppressing miR-29a-Mediated EndMT.

Diabetic nephropathy is the leading cause of kidney fibrosis. Recently, altered expressed or dysfunction of some long non-coding RNAs (lncRNAs) has been linked to kidney fibrosis; however, the mechanisms of lncRNAs in kidney fibrosis remain unclear. We have shown that the DPP-4 inhibitor linagliptin can inhibit endothelial-mesenchymal transition (EndMT) and ameliorate diabetic kidney fibrosis associated with DPP-4 protein levels via the induction of miR-29. Here, we found that expression of the lncRNA H19 was significantly up-regulated in TGF-ß2-induced fibrosis in human dermal microvascular endothelial cells (HMVECs) in vitro, and in kidney fibrosis of streptozotocin-induced diabetic CD-1 mice. We also detected up-regulated H19 expression and down-regulated miR-29a expression in the early and advanced mouse models of diabetic kidney fibrosis. H19 knockdown significantly attenuated kidney fibrosis in vitro and in vivo, which was associated with the inhibition of the EndMT-associated gene FSP-1. We also found that the up-regulation of H19 observed in fibrotic kidneys associated with the suppression of miR-29a in diabetic mice. H19, miR-29a, and EndMT contribute to a regulatory network involved in kidney fibrosis, and are associated with regulation of the TGF-ß/SMAD3 singling pathway. This study indicates that inhibition of LncRNA H19 represents a novel anti-fibrotic treatment for diabetic kidney diseases.

Microscopic Mechanism of Carbon-Dopant Manipulating Device Performance in CGeSbTe-Based Phase Change Random Access Memory.

Carbon (C)-doped Ge2Sb2Te5 material is a potential candidate in phase change random access memory (PCRAM) because of its superb thermal stability and ultrahigh cycle endurance. Unfortunately, the role and distribution evolution of C-dopant is still not fully understood, especially in practical industrial devices. In this report, with the aid of advanced spherical aberration corrected transmission electron microscopy, the mechanism of microstructure evolution manipulated by C-dopant is clearly defined. The grain-inner C atoms distinctly increase cationic migration energy barriers, which is the fundamental reason for promoting the thermal stability of metastable face-centered-cubic phase and postponing its transition to the hexagonal structure. By current pulses stimulation, the stochastic grain-outer C clusters tend to aggregate in the active area by breaking C-Ge bonding; thus, grain growth and elemental segregation are effectively suppressed to improve device reliability, for example, lower SET resistance, shorter SET time, and enlarged RESET/SET ratio. In short, the visual distribution variations of C-dopant can manipulate the performance of the PCRAM device, having much broader implications for optimizing its microstructure transition and understanding C-doped material system.

[Clinical study of concealed penis correction surgery based on principle of midline symmetry].

OBJECTIVE: To investigate the effectiveness of concealed penis correction surgery based on the principle of midline symmetry. METHODS: Between January 2016 and September 2018, 18 children with concealed penis were treated with correction surgery based on the principle of midline symmetry. All children were 3-12 years old, with an average age of 8.3 years. Physical examination showed that the penis was short; the penis body could not be exposed or be exposed too limited; the corpus cavernosum developed well. The pressure dressing was removed at 3 days after operation and the urethral tube was removed. The color of the glans, the swelling and congestion of penis and scrotum, and the blood supple of the prepuce flap were observed. RESULTS: The operation time ranged from 47 to 54 minutes, with an average of 50 minutes. All children were followed up 3 months after operation. There was no hemorrhage and necrosis of the glans and no infection or ischemic necrosis of the flap. All patients had different degree of prepuce edema at 3 days after operation, 5 patients still had prepuce edema at 2 weeks, and the prepuce edema in all patients subsided at 3 months. All penises were exposed well after midline symmetric anastomosis with no bulky prepuce and scrotum. CONCLUSION: The correction surgery based on the principle of midline symmetry can be used to correct the appearance of the concealed penis effectively.

Enhance the Discrimination Precision of Graphene Gas Sensors with a Hidden Markov Model.

Sensors are the key element to enable smart electronics and will play an important role in the emerging big data era. In this work, we reported an experimental study and a data-analytical characterization method to enhance the precision of discriminating chemically and structurally similar gases. Graphene sensors were fabricated by conventional photolithography and measured with feature analysis against different chemicals. A new hidden Markov model assisted with frequency spectral analysis, and the Gaussian mixture model (K-GMM-HMM) is developed to discriminate similar gases. The results indicated that the new method achieved a high prediction accuracy of 94%, 27% higher than the maximum value obtained by the conventional methods or other feature transient analysis methods. This study indicated that graphene gas sensors with the new K-GMM-HMM analysis are very attractive for chemical discrimination used in future smart electronics.

Excellent thermal stability owing to Ge and C doping in Sb2Te-based high-speed phase-change memory.

The contradictory nature between transition speed and thermal stability of phase-change materials has always been the key limitation to the achievement of wide applications under harsh conditions. Ge2.3Sb2.0Te phase-change alloy is proposed here to feature high thermal stability (10 year data retention above 220 °C) and fast switching speed (SET programming speed up to 5 ns) for electronic storage. In mushroom-shaped device cells, the nanocomposite materials implement an endurance life of nearly 1 × 105 cycles. Such operation speed among high-temperature alloys is the best ever reported. And the moderate incorporation of C offers intriguing benefits that include enhanced thermal stability and reduced RESET voltage in the above-mentioned Ge-rich Sb2Te-based memory cells. Through microscopic analysis, the local segregation of C dopants can further refine the crystalline grains and thus induce a lower volume change and roughness upon heating. These properties are crucial with regard to the application potential in high-performance and high-density embedded memories.

Serine 105 and 120 are important phosphorylation sites for porcine reproductive and respiratory syndrome virus N protein function.

The nucleocapsid (N) protein is the most abundant protein of porcine reproductive and respiratory syndrome virus (PRRSV). It has been shown to be multiphosphorylated. However, the phosphorylation sites are still unknown. In this study, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) to analyze the phosphorylation sites of N protein expressed in Sf9 cells. The results showed that N protein contains two phosphorylation sites. Since N protein can regulate IL-10, which may facilitate PRRSV replication, we constructed four plasmids (pCA-XH-GD, pCA-A105, pCA-A120 and pCA-A105-120) and transfected them into Pig alveolar macrophages (PAMs,3D4/2). The qPCR results showed that mutations at residues 105 and 120 were associated with down-regulation of the IL-10 mRNA level, potentially decreasing the viral growth ability. Then, we mutated the phosphorylation sites (S105A and S120A) and rescued three mutated viruses, namely, A105, A120 and A105-120. Compared with wild-type virus titers, the titers of the mutated viruses at 48 hpi were significantly decreased. The Nsp(non-structural protein) 9 qPCR results were consistent with the multistep growth kinetics results. The infected PAMs (primary PAMs) results were similar with Marc-145.The findings indicated that the mutations impaired the viral replication ability. The confocal microscopy results suggested that mutations to residues 105 and 120 did not affect N protein distribution. Whether the mutations affected other functions of N protein and what the underlying mechanisms are need further investigation. In conclusion, our results show that residues 105 and 120 are phosphorylation sites and are important for N protein function and for viral replication ability.

Sparse Optimistic Based on Lasso-LSQR and Minimum Entropy De-Convolution with FARIMA for the Remaining Useful Life Prediction of Machinery.

To reduce the maintenance cost and safeguard machinery operation, remaining useful life (RUL) prediction is very important for long term health monitoring. In this paper, we introduce a novel hybrid method to deal with the RUL prediction for health management. Firstly, the sparse reconstruction algorithm of the optimized Lasso and the Least Square QR-factorization (Lasso-LSQR) is applied to compressed sensing (CS), which can realize the sparse optimization for long term health monitoring data. After the sparse signal is reconstructed, the minimum entropy de-convolution (MED) is used to identify the fault characteristics and to obtain significant fault information from the machinery operation. Health indicators with Skip-over, sample entropy and approximate entropy are then performed to track the degradation of the machinery process. The performance analysis of the Skip-over is superior to other indicators. Finally, Fractal Autoregressive Integrated Moving Average model (FARIMA) is employed to predict the Skip-over using the R/S method. The analysis results evidence that the novel hybrid method yields a good performance, and such method can achieve highly accurate RUL prediction and safeguard machinery operation for long term monitoring.

Reducing the stochasticity of crystal nucleation to enable subnanosecond memory writing.

Operation speed is a key challenge in phase-change random-access memory (PCRAM) technology, especially for achieving subnanosecond high-speed cache memory. Commercialized PCRAM products are limited by the tens of nanoseconds writing speed, originating from the stochastic crystal nucleation during the crystallization of amorphous germanium antimony telluride (Ge2Sb2Te5). Here, we demonstrate an alloying strategy to speed up the crystallization kinetics. The scandium antimony telluride (Sc0.2Sb2Te3) compound that we designed allows a writing speed of only 700 picoseconds without preprogramming in a large conventional PCRAM device. This ultrafast crystallization stems from the reduced stochasticity of nucleation through geometrically matched and robust scandium telluride (ScTe) chemical bonds that stabilize crystal precursors in the amorphous state. Controlling nucleation through alloy design paves the way for the development of cache-type PCRAM technology to boost the working efficiency of computing systems.

Surface Energy Driven Cubic-to-Hexagonal Grain Growth of Ge2Sb2Te5 Thin Film.

Phase change memory (PCM) is a promising nonvolatile memory to reform current commercial computing system. Inhibiting face-centered cubic (f-) to hexagonal (h-) phase transition of Ge2Sb2Te5 (GST) thin film is essential for realizing high-density, high-speed, and low-power PCM. Although the atomic configurations of f- and h-lattices of GST alloy and the transition mechanisms have been extensively studied, the real transition process should be more complex than previous explanations, e.g. vacancy-ordering model for f-to-h transition. In this study, dynamic crystallization procedure of GST thin film was directly characterized by in situ heating transmission electron microscopy. We reveal that the equilibrium to h-phase is more like an abnormal grain growth process driven by surface energy anisotropy. More specifically, [0001]-oriented h-grains with the lowest surface energy grow much faster by consuming surrounding small grains, no matter what the crystallographic reconfigurations would be on the frontier grain-growth boundaries. We argue the widely accepted vacancy-ordering mechanism may not be indispensable for the large-scale f-to-h grain growth procedure. The real-time observations in this work contribute to a more comprehensive understanding of the crystallization behavior of GST thin film and can be essential for guiding its optimization to achieve high-performance PCM applications.

Reversible Phase Change Characteristics of Cr-Doped Sb2Te3 Films with Different Initial States Induced by Femtosecond Pulses.

As a kind of chalcogenide alloy, phase change material has been widely used as novel storage medium in optical disk or electrical memory. In this paper, femtosecond pulses are used to study the reversible phase transition processes of Cr-doped Sb2Te3 films with different initial states. The SET processes are all induced by multiple pulses and relate to the increase of crystallized partial in the irradiated spot. When the Cr concentration is 5.3 at % or 10.5 at %, the crystallization mechanism is still growth-dominated as Sb2Te3, which is beneficial for high speed and high density storage, whereas the necessary crystallization energy increases with more Cr-dopants, leading to higher amorphous thermal stability. RESET results by multiple pulses show that Cr-dopants will not increase the power consumption, and the increase in Cr-dopants could greatly increase the antioxidant capacity. Single-pulse experiments show that the RESET process involves the competition of melting/amorphization and recrystallization. The reversible SET/RESET results on different initial states are quite different from each other, which is mainly due to the different surroundings around the irradiated spot. Crystalline surroundings provide higher thermal conductivity and lead to easier crystallization, whereas amorphous surroundings were the reverse. All in all, Cr-doped Sb2Te3 films with suitable composition have advantages for storage with high density, better thermal stability, and lower power consumption; and the suitable initial states could ensure better reversible phase transition performances.

Direct observation of titanium-centered octahedra in titanium-antimony-tellurium phase-change material.

Phase-change memory based on Ti0.4Sb2Te3 material has one order of magnitude faster Set speed and as low as one-fifth of the Reset energy compared with the conventional Ge2Sb2Te5 based device. However, the phase-transition mechanism of the Ti0.4Sb2Te3 material remains inconclusive due to the lack of direct experimental evidence. Here we report a direct atom-by-atom chemical identification of titanium-centered octahedra in crystalline Ti0.4Sb2Te3 material with a state-of-the-art atomic mapping technology. Further, by using soft X-ray absorption spectroscopy and density function theory simulations, we identify in amorphous Ti0.4Sb2Te3 the titanium atoms preferably maintain the octahedral configuration. Our work may pave the way to more thorough understanding and tailoring of the nature of the Ti-Sb-Te material, for promoting the development of dynamic random access memory-like phase-change memory as an emerging storage-class memory to reform current memory hierarchy.

Understanding the crystallization behavior of as-deposited Ti-Sb-Te alloys through real-time radial distribution functions.

Phase change materials, successfully used in optical data-storage and non-volatile electronic memory, are well-known for their ultrafast crystallization speed. However, the fundamental understanding of their crystallization behavior, especially the nucleation process, is limited by present experimental techniques. Here, real-time radial distribution functions (RDFs), derived from the selected area electron diffractions, are employed as structural probes to comprehensively study both nucleation and subsequent growth stages of Ti-doped Sb2Te3 (TST) materials in the electron-irradiation crystallization process. It can be found that the incorporation of Ti atoms in Sb2Te3 forms wrong bonds such as Ti-Te, Ti-Sb, breaks the originally ordered atomic arrangement and diminishes the initial nucleus size of the as-deposited films, which results in better thermal stability. But these nuclei hardly grow until their sizes exceed a critical value, and then a rapid growth period starts. This means that an extended nucleation time is required to form the supercritical nuclei of TST alloys with higher concentration. Also, the increasing formation of four-membered rings, which served as nucleation sites, after doping excessive Ti is responsible for the change of the crystallization behavior from growth-dominated to nucleation-dominated.

Phase-change properties of GeSbTe thin films deposited by plasma-enchanced atomic layer depositon.

Phase-change access memory (PCM) appears to be the strongest candidate for next-generation high-density nonvolatile memory. The fabrication of ultrahigh-density PCM depends heavily on the thin-film growth technique for the phase-changing chalcogenide material. In this study, Ge2Sb2Te5 (GST) and GeSb8Te thin films were deposited by plasma-enhanced atomic layer deposition (ALD) method using Ge [(CH3)2 N]4, Sb [(CH3)2 N]3, Te(C4H9)2 as precursors and plasma-activated H2 gas as reducing agent of the metallorganic precursors. Compared with GST-based device, GeSb8Te-based device exhibits a faster switching speed and reduced reset voltage, which is attributed to the growth-dominated crystallization mechanism of the Sb-rich GeSb8Te films. These results show that ALD is an attractive method for preparation of phase-change materials.

Understanding phase-change behaviors of carbon-doped Ge2Sb2Te5 for phase-change memory application.

Phase-change materials are highly promising for next-generation nonvolatile data storage technology. The pronounced effects of C doping on structural and electrical phase-change behaviors of Ge2Sb2Te5 material are investigated at the atomic level by combining experiments and ab initio molecular dynamics. C dopants are found to fundamentally affect the amorphous structure of Ge2Sb2Te5 by altering the local environments of Ge-Te tetrahedral units with stable C-C chains. The incorporated C increases the amorphous stability due to the enhanced covalent nature of the material with larger tetrahedral Ge sites. The four-membered rings with alternating atoms are reduced greatly with carbon addition, leading to sluggish phase transition and confined crystal grains. The lower RESET power is presented in the PCM cells with carbon-doped material, benefiting from its high resistivity and low thermal conductivity.

One order of magnitude faster phase change at reduced power in Ti-Sb-Te.

To date, slow Set operation speed and high Reset operation power remain to be important limitations for substituting dynamic random access memory by phase change memory. Here, we demonstrate phase change memory cell based on Ti0.4Sb2Te3 alloy, showing one order of magnitude faster Set operation speed and as low as one-fifth Reset operation power, compared with Ge2Sb2Te5-based phase change memory cell at the same size. The enhancements may be rooted in the common presence of titanium-centred octahedral motifs in both amorphous and crystalline Ti0.4Sb2Te3 phases. The essentially unchanged local structures around the titanium atoms may be responsible for the significantly improved performance, as these structures could act as nucleation centres to facilitate a swift, low-energy order-disorder transition for the rest of the Sb-centred octahedrons. Our study may provide an alternative to the development of high-speed, low-power dynamic random access memory-like phase change memory technology.

Application of three-step epitaxial process to dual trench epitaxial diode array.

The application of three-step Epitaxial (EPI) process to dual trench epitaxial diode array for high density phase change random access memory (PCRAM) was reported in this paper. With three-step EPI process condition, both vertical and lateral Arsenic auto-doping were suppressed effectively from Arsenic heavily-doped substrate. It was found that EPI layer (- 300 nm) with high-quality single crystalline and good thickness uniformity within 200 mm diameter wafer could be achieved. It was also found that both lateral and vertical Arsenic auto-doping concentration could be reduced by 2-3 orders by adding high temperature and low deposition rate EPI step before main EPI process, as compared to the conventional CVD EPI process. As a result, diode breakdown voltage was improved above 11 V and the On/Off current ratio of diode is greater than 9 orders of magnitude.

Reactive ion etching of Si(x)Sb2Te in CF4/Ar plasma for nonvolatile phase-change memory device.

Si(x)Sb2Te material system is novel for phase-change random access memory applications. Its properties are more outstanding than the widely used material Ge2Sb2Te5. Etching process is one of the critical steps in the device fabrication. The etching characteristics of phase-change material Si(x)Sb2Te were studied with CF4/Ar gas mixture by a reactive ion etching system. The changes of etching rate, etching profile and surface root-mean-square roughness resulted from variation of the gas-mixing ratio were investigated under constant pressure (50 mTorr) and applying power (200 W). Si0.34Sb2Te is with the highest phase-change speed and the lowest power consumption in the PCRAM memory among these compositions, which means it is the most promising candidate for the PCRAM applications. So the most optimized CF4/Ar gas ratio for Si0.34Sb2Te was studied, the value is 25/25. The etching rate is 155 nm/min, and the selectivity of Si0.34Sb2Te to SiO2 is as high as 3.4 times. Furthermore, the smooth surface was achieved with this optimized gas ratio.

Design of side bottom-electrode-contact for high density phase-change memory array.

In this work, a high density phase-change memory (PCM) array with advanced side bottom-electrode-contact (BEC) scheme, which is highly compatible with current complementary metal oxide semiconductor technology, has been proposed. The data storage capacity has been doubled than orthodoxy PCM structure and the contact area between bottom electrode and PCM cell shrinks from 20096 nm2 to 600 nm2. The optimized titanium nitride (TiN) film as side BEC is 10 nm due to trading off between RESET current and SET resistance. As simulation results presented, the PCM cell with optimized side BEC thickness shows lower SET current of 0.06 mA, lower RESET current of 0.24 mA and higher resistance ratio of 10(3) between amorphous and crystalline phases. This side BEC process scheme is cost-effective process accompanying with tungsten via formation to minimize programming power. Meanwhile, based on the three-dimensional (3D) side BEC numerical model, it is manifested that there is cross-talk immunity in adjacent PCM cells during programming.