Modeling for High-Frequency Spurious Responses in Incredible High-Performance Surface Acoustic Wave Devices.

To ensure that surface acoustic wave (SAW) filters fulfill the requirements of Carrier Aggregation (CA) applications, the development of modeling tools that can forecast and simulate high-frequency spurious responses has been necessary. This paper presents an advanced methodology for extending the coupling-of-modes (COM) model to obtain precise modeling of the high-frequency spurious responses of incredible high-performance surface acoustic wave (I.H.P. SAW) devices. The extended COM (ECOM) model is derived by modifying the conventional COM model and extending it accordingly. The parameters used in this model are determined through numerical fitting. For validation, firstly, the ECOM model is applied to a one-port synchronous I.H.P. SAW resonator, and the simulation and measurement results match. Then, the structural parameters of the ECOM model are varied, and the accuracy of the model after the structural parameters are varied is verified. It is demonstrated that this model can be applied to the design work of SAW filters. Finally, the ECOM model is applied to the design of the I.H.P. SAW filter based on a 42°YX-LiTaO3 (LT)/SiO2/AlN/Si structure. By using this method, the I.H.P. SAW filter's high-frequency spurious response can be predicted more accurately.

An Infrared Near-Sensor Reservoir Computing System Based on Large-Dynamic-Space Memristor with Tens of Thousands of States for Dynamic Gesture Perception.

To efficiently process the massive amount of sensor data, it is demanding to develop a new paradigm. Inspired by neurobiological systems, an infrared near-senor reservoir computing (RC) system, consisting of infrared sensors and memristors based on single-crystalline LiTaO3 and LiNbO3 (LN) thin film respectively, is demonstrated. The analog memristor is used as a reservoir in the RC system to process sensor signals with spatiotemporal characteristics. LN crystal structure stacked with oxygen octahedra provides favorable conditions for reliable Mott variable-range hopping conduction, which provides the memristor with tens of thousands of reservoir states within a large dynamic range. With the characteristics, the analog sensor signals with high data fidelity can be directly fed to the memristive reservoir, and the spatiotemporal features can be separated and mapped. The system demonstrated a dynamic gesture perception task, achieving an accuracy of 99.6%, which highlights the great application potential of the memristor in signal sensor processing and will advance the application of artificial intelligence in sensor systems. Crystal ion slicing techniques are used to fabricate a single-crystalline thin film for both the memristor and sensor, which opens up the possibility of realizing monolithic integration of a memristor-based near-sensor computing system.

Designed Structures of Interdigital Electrodes for Thin Film SAW Devices.

This paper studied the impact of the microstructure of interdigital electrodes on the performance of surface acoustic wave (SAW) resonators and proposed an innovative piston, dummy finger and tilt (PDT) structure, which was then applied to the GLONASS L3 band filters. Through the adoption of 3D finite element simulation (FEM), photolithography, and testing on an incredible high-performance surface acoustic wave (I.H.P. SAW) substrate, it is concluded that the total aperture length is 20T (T is period), resulting in a more optimal resonator performance; changing the width and length of the piston can suppress transverse modes spurious, but it does not enhance impedance ratio; to further improve the quality of the SAW resonator, the proposed PDT structure has been experimentally proven to not only effectively suppress transverse modes spurious but also possess a high impedance ratio. By utilizing a PDT structure within a "T + π" topology circuit, we successfully designed and manufactured a GLONASS L3 band filter with a bandwidth of 8 MHz and an insertion loss of 3.73 dB. The design of these resonators and filters can be applied to the construction of SAW filters in similar frequency bands such as BeiDou B2 band or GPS L2/L5 band.

Controllable modulation of the oxygen vacancy-induced adjustment of memristive behavior for direct differential operation with transistor-free memristor.

To achieve the goal of neuromorphic computing hardware implementation with extremely high efficiency, low power consumption, and high density, it is necessary to develop transistor-free memristors and implement differential operation without subtraction circuits. In this study, argon ion irradiation was used during the fabrication process of a single crystalline LiNbO3 (LN) thin film to controllably introduce oxygen vacancies (OVs) into the bottom surface, which realized the modulation of OVs based on the excellent environment provided by a single-crystalline thin film. The memristive behavior of memristors was then modulated by regulating the distribution of OVs, and the effect of OVs distributed near the bottom surface of the single crystalline LN thin film on the memristive behavior was analyzed. In this way, two transistor-free memristors with opposite memristive behavior directions were fabricated. Two transistor-free memristors exhibit excellent synaptic plasticity and reliable multilevel resistance states. Based on two transistor-free memristors, a novel differential pair was constructed. Hardware implementations of direct differential operation without subtraction circuits were achieved. This study provides a new pathway to develop a transistor-free memristor and achieve differential operation without subtraction circuits in neuromorphic computing, which will simplify the peripheral circuits, improve integration density, and reduce power consumption and latency.

Personalized demand-responsive biphasic microneedle patch for smart drug administration.

Many patients, especially those with chronic diseases, would benefit from personalized drugs that could modulate the treatment regimen. Tailored drug delivery via microneedle patches (MNPs) has emerged as a promising technology to address this problem. However, it is still difficult to modulate the treatment regimen in one MNP. Here, multiple treatment regimens were achieved by the same MNP functionalized with modifiable nanocontainers (NCs). The MNPs were biphasic in design, resulting in approximately a twice as high drug loading capacity than that of traditional dissolving MNPs. The drug-loaded NCs could have a zero-order release rate for at least 20 d in vitro. Furthermore, three model MNPs, Type-A (100% drug), Type-B (50% drug and 50% NCs) and Type-C (100% NCs) were generated to simulate various personalized dosing needs. In vivo application of these models could achieve effective therapeutic drug concentrations in the first 12 h and adjusted the duration of effective drug action from 24 h to 96 h and 144 h, respectively, with outstanding biocompatibility. These findings indicate that this device holds significant promise for personalized drug delivery.

Poly-G for tumor matched samples chronicles the evolution of human colorectal cancer / 中华肿瘤杂志

Objective: To analyze poly-guanine (poly-G) genotypes and construct the phylogenetic tree of colorectal cancer (CRC) and provide an efficient and convenient method for the study of intra-tumor heterogeneity and tumor metastasis pathway. Methods: The clinicopathological information of patients with primary colorectal cancer resection with regional lymph node metastases were retrospectively collected in the Department of General Surgery, General Hospital of Tianjin Medical University from January 2017 to December 2017. The paraffin sections of the paired tumor samples were performed consecutively, and multi-region microdissection was performed after histogene staining. The phenol-chloroform extraction and ethanol precipitation scheme was used to obtain DNA, and Poly-G multiplex PCR amplification and capillary electrophoresis detection were performed. The correlation between Poly-G mutation frequency and clinicopathological parameters was analyzed. Based on the difference of Poly-G genotypes between paired samples, the distance matrix was calculated, and the phylogenetic tree was constructed to clarify the tumor metastasis pathway. Results: A total of 237 paired samples were collected from 20 patients including 134 primary lesions, 66 lymph node metastases, 37 normal tissues, and Poly-G mutation was detected in 20 patients (100%). The mutation frequency of Poly-G in low and undifferentiated patients was (74.10±23.11)%, higher than that in high and medium differentiated patients [(31.36±12.04)%, P<0.001]. In microsatellite instability patients, the mutation frequency of Poly-G was (68.19±24.80)%, which was higher than that in microsatellite stable patients [(32.40±14.90)%, P=0.003]. The Poly-G mutation frequency was not correlated with age, gender, and pathological staging (all P>0.05). Based on Poly-G genotype difference of the paired samples, the phylogenetic trees of 20 patients were constructed, showing the evolution process of the tumor, especially the subclonal origins of lymph node metastasis. Conclusion: Poly-G mutations accumulate in the occurrence and development of CRC, and can be used as genetic markers to generate reliable maps of intratumor heterogeneity in large numbers of patients with minimal time and cost expenditure.

Effect of down-regulation of let-7c/g on triggering a double-negative feedback loop and promoting restenosis / 中华医学杂志(英文版)

BACKGROUND@#Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) are the main causes of restenosis (RS) in diabetic lower extremity arterial disease (LEAD). However, the relevant pathogenic mechanisms are poorly understood.@*METHODS@#In this study, we introduced a "two-step injury protocol" rat RS model, which started with the induction of atherosclerosis (AS) and was followed by percutaneous transluminal angioplasty (PTA). Hematoxylin-eosin (HE) staining and immunohistochemistry staining were used to verify the form of RS. Two-step transfection was performed, with the first transfection of Lin28a followed by a second transfection of let-7c and let-7g, to explore the possible mechanism by which Lin28a exerted effects. 5-ethynyl-2΄-deoxyuridine (EdU) and Transwell assay were performed to evaluate the ability of proliferation and migration of VSMCs. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the expression of Lin28a protein and let-7 family members.@*RESULTS@#Using a combination of in vitro and in vivo experiments, we discovered that let-7c, let-7g, and microRNA98 (miR98) were downstream targets of Lin28a. More importantly, decreased expression of let-7c/let-7g increased Lin28a, leading to further inhibition of let-7c/let-7g. We also found an increased level of let-7d in the RS pathological condition, suggesting that it may function as a protective regulator of the Lin28a/let-7 loop by inhibiting the proliferation and migration of VSMCs.@*CONCLUSION@#These findings indicated the presence of a double-negative feedback loop consisting of Lin28a and let-7c/let-7g, which may be responsible for the vicious behavior of VSMCs in RS.

BAW Resonator with an Optimized SiO2/Ta2O5 Reflector for 5G Applications.

In the present work, a lithium niobate (LN) 43°Y cut LN film is transferred onto a substrate with 11 layers of SiO2/Ta2O5 and solidly mounted resonators with a reflector are successfully fabricated with the multilayer structure. The design method and fabrication process are demonstrated. The finite element model and the Mason model are used. Scanning electron microscopy and atomic force microscopy are used to characterize film quality. An optimized design of a Bragg reflector to suppress the leakage of acoustic energy by thickness shear mode is proven to be effective. The influence of the reflector on parasitic modes and filter out-of-band suppression is analyzed. The resonator for 3.5 GHz shows an effective electromechanical coupling coefficient of 17.9%, and the figure of merit is 40.4, which is suitable for band pass filter on the N78 band with high rejection.

Wide Band BAW Filter Based on Single-Crystalline LiNbO3 Thin Film With Insulating Bragg Reflector.

Bulk acoustic wave (BAW) filter with large bandwidth is an urgent need in fifth-generation (5G) communication systems. In the present work, 43° Y-cut lithium niobate (LN) single-crystal film is prepared on multilayer oxide film, and bulk acoustic filter with oxide Bragg reflector (BR) is successfully achieved. The design method of the filter and the fabrication process are presented. Atomic force microscope (AFM) and scanning electron microscope (SEM) are used to characterize the quality of thin films. The results demonstrate the feasibility of transferring single-crystal film onto multilayer oxide, which is efficient for the confinement of acoustic energy. The resonator has effective electromechanical coupling coefficient of 14.6% and figure of merit (FOM) of 32.94. The filter with a compact size of 600 [Formula: see text] has a relative bandwidth of 10.3% at a center frequency of 3.128 GHz, which is promising for the application of 5G systems.

Deep chemical identification of phytoecdysteroids in Achyranthes bidentata Blume by UHPLC coupled with linear ion trap-Orbitrap mass spectrometry and targeted isolation / 中国天然药物

Achyranthes bidentata Blume is widely used as a traditional Chinese medicine with the effects of nourishing the liver and kidneys and strengthening muscles and bones. In this work, a rapid and simple strategy was developed for characterizing phytoecdysteroids by ultra-high-performance liquid chromatography coupled with liner ion trap-Orbitrap mass spectrometry using electrospray ionization in the negative mode. As a result, 47 phytoecdysteroids were unambiguously or tentatively characterized. Among them, seven known compounds were identified according to the reference standards along with molecular formula, retention time and fragmentation patterns, while others were mostly potential new compounds. Through targeted isolation, the structures of three new compounds were determined by NMR spectra, which were consistent with LC-MS characterization. The present study provides an efficient method to deeply characterize phytoecdysteroids.

Identification of chemical constituents of Xiaochengqi Decoction by UPLC-Q-TOF/Fast DDA combined with UNIFI software / 中国中药杂志

Based on the combination of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF) and Waters UNIFI software, the chemical constituents of the classic prescription Xiaochengqi Decoction were qualitatively analyzed and identified. The UPLC conditions are as follows: Acquity HSS T3 reverse phase column(2.1 mm ×100 mm, 1.8 μm), column temperature of 30 ℃, mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B), and flow rate of 0.3 mL·min~(-1). High-resolution MS data of Xiaochengqi Decoction were collected in ESI~(+/-) modes by Fast DDA. The structures of the chemical constituents were tentatively characterized or identified by UNIFI software according to the retention time of reference standards and characteristic fragment ions in MS profile, and literature data. A total of 233 components in Xiaochengqi Decoction were identified, with 93 from wine-processed Rhei Radix et Rhizoma, 104 from bran-processed Aurantii Fructus Immaturus, and 36 from ginger-processed Magnoliae Officinalis Cortex. These 233 components included anthraquinones, flavonoids, lignans, alkaloids, coumarins, and phenylethanoid glycosides. The result provided experimental evidence for the further study on establishment of quality standard and product development of the formula.

Gait abnormalities among elderly persons with type 2 diabetes and peripheral neuropathy / 中华物理医学与康复杂志

Objective:To explore the features the gait of elderly persons with type 2 diabetes and peri-pheral neuropathy.Methods:Twenty patients no less than 60 years old with type 2 diabetes and peripheral neuropathy (DPN) formed a DPN group, while 20 counterparts with type 2 diabetes but without peripheral neuropathy composed the DM group, and another 20 healthy counterparts served as a control group. The three groups were tested using the Swedish Qualisys motion capture system and their walking speed, step length, step width, stride frequency and stride length, bipedal foot support phase time, single foot support phase time, peak plantar pressure, and regional-holding time were collected and compared.Results:The average walking speed, stride length and stepping frequency of the DPN group were all significantly lower than the other 2 groups′ averages. Their bipedal support phase was significantly longer, but their single foot support phase time was significantly shorter. And in the DPN group the average first and second peak plantar pressures and the second peak pressure time were significantly greater than the other groups′ averages.Conclusions:Elderly patients with type 2 diabetes and peripheral neuropathy have significant gait abnormalities, decreased walking stability, as well as increased plantar pressure and plantar compression time.

Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

A Solidly Mounted Resonator Fabricated by LiNbO3 Single-Crystalline Film on Flexible Polyimide Substrate.

A solidly mounted resonator on flexible polyimide (PI) substrate with high-effective coupling coefficient ( Kt2 ) of 14.06% is reported in this article. This high Kt2 is resulting from the LiNbO3 (LN) single-crystalline film and [SiO2/Mo]3 Bragg reflector. The quality of LN film fabricated by the crystal-ion-slicing (CIS) technique using benzocyclobutene (BCB) bonding layer was close to the bulk crystalline LN. The interfaces of the Al/LN/Al/[SiO2/Mo]3 Bragg reflector/BCB/PI multilayer are sharp, and the thickness of each layer is consistent with its design value. The resonant frequency and Kt2 keep stable when it is bent at different radii. These results demonstrate a feasible approach to realizing RF filters on flexible polymer substrates, which is an indispensable device for building integrated and multifunctional wireless flexible electronic systems.

Novel Method for the Quantitative Analysis of Protease Activity: The Casein Plate Method and Its Applications.

No simple methods are used for the quantitative analysis of the protease activity in colored food up till now. Thus, this study aims to establish a new and simple method for the quantitative detection of protease activity, especially in colored food. The detection accuracy, detection limit, and repeatability of the casein plate method were analyzed. Then, the application of the casein plate method in sample detection and recovery was further evaluated. The results showed that the casein plate method for the quantitative detection of protease activity has high accuracy, high precision, and low detection limit. The recoveries of eight kinds of colored samples were in the range of 92.26-97.84%, and the relative standard deviation (RSD) was in the range of 3.56-10.88%. The results of the casein plate method exhibited high accuracy. This indicated that the method was suitable for the detection of colored samples. The casein plate method for the quantitative detection of protease activity is simple. The newly constructed casein plate method has broad potential application value in food industry, especially for the detection of dark food.

Simple and robust differentiation of Ganoderma species by high performance thin-layer chromatography coupled with single quadrupole mass spectrometry QDa / 中国天然药物

In this study, a high performance thin-layer chromatography/single quadrupole mass spectrometry QDa (HPTLC-QDa) method for robust authentication of Ganoderma lucidum, a popular and valuable herbal medicine, has been developed. This method is simple and practical, which allows direct generation of characteristic mass spectra from the HPTLC plates automatically with the application of in situ solvent desorption interface. The HPTLC silica gel plates were developed with toluene-ethyl formate-formic acid (5 : 5 : 0.2, V/V) and all bands were transferred to QDa system directly in situ using 80% methanol with 0.1% formic acid as desorption solvent. The acquired HPTLC-QDa spectra showed that luminous yellow band b3, containing ganoderic acid B/G/H and ganodeneric acid B, the major active components of Ganoderma, could be found only in G. lucidum and G. lucidum (Antler-shaped), but not in G. sinense and G. applanatum. Moreover, bands b13 and b14 with m/z 475/477 and m/z 475/491/495, respectively, could be detected in G. lucidum (Antler-shaped), but not in G. lucidum, thus allowing simple and robust authentication of G. lucidum with confused species. This method is proved to be simple, practical and reproducible, which can be extended to analyze other herbal medicines.

Record-Low Subthreshold-Swing Negative-Capacitance 2D Field-Effect Transistors.

Power consumption is one of the most challenging bottlenecks for complementary metal-oxide-semiconductor integration. Negative-capacitance field-effect transistors (NC-FETs) offer a promising platform to break the thermionic limit defined by the Boltzmann tyranny and architect energy-efficient devices. However, it is a great challenge to achieving ultralow-subthreshold-swing (SS) (10 mV dec-1 ) and small-hysteresis NC-FETs simultaneously at room temperature, which has only been reported using the hafnium zirconium oxide system. Here, based on a ferroelectric LiNbO3 thin film with great spontaneous polarization, an ultralow-SS NC-FET with small hysteresis is designed. The LiNbO3 NC-FET platform exhibits a record-low SS of 4.97 mV dec-1 with great repeatability due to the superior capacitance matching characteristic as evidenced by the negative differential resistance phenomenon. By modulating the structure and operating parameters (such as channel length (Lch ), drain-sourse bias (Vds ), and gate bias (Vg )) of devices, an optimized SS from ≈40 to ≈10 mV dec-1 and hysteresis from ≈900 to ≈60 mV are achieved simultaneously. The results provide a new potential method for future highly integrated electronic and optical integrated energy-efficient devices.

Macromolecules and Antibody-Based Drugs.

Macromolecule drugs particularly antibody drugs are very powerful therapies developing rapidly in the recent 20 years, providing hopes for many patients diagnosed with "incurable" diseases in the past. They also provide more effective and less side effects for many afflicting diseases, and greatly improve the survival rate and life quality of patients. In the last two decades, the proportion of US Food and Drug Administration (FDA) approved macromolecules and antibody drugs are increasing quickly, especially after the discovery of immune checkpoints. To crown all, the 2017 Nobel prize in physiology or medicine was given to immunotherapy. In this chapter, we would like to summarize the current situation of macromolecule and antibody drugs, and what effort scientists and pharmaceutical industry have made to discover and manufacture better antibody drugs.

Engineering of self-rectifying filamentary resistive switching in LiNbO3 single crystalline thin film via strain doping.

The abilities to fabricate wafer scale single crystalline oxide thin films on metallic substrates and to locally engineer their resistive switching characteristics not only contribute to the fundamental investigations of the resistive switching mechanism but also promote the practical applications of resistive switching devices. Here, wafer scale LiNbO3 (LNO) single crystalline thin films are fabricated on Pt/SiO2/LNO substrates by ion slicing with wafer bonding. The lattice strain of the LNO single crystalline thin films can be tuned by He implantation as indicated by XRD measurements. After He implantation, the LNO single crystalline thin films show self-rectifying filamentary resistive switching behaviors, which is interpreted by a model that the local conductive filaments only connect/disconnect with the bottom interface while the top interface maintains the Schottky contact. Thanks to the homogeneous distribution of defects in single crystalline thin films, highly reproducible and uniform self-rectifying resistive switching with large on/off ratio over four order of magnitude was achieved. Multilevel resistive switching can be obtained by varying the compliance current or by using different magnitude of writing voltage.