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Abstract Background The application of cerebellar transcranial magnetic stimulation (TMS) in stroke patients has received increasing attention due to its neuromodulation mechanisms. However, studies on the effect and safety of cerebellar TMS to improve balance capacity and activity of daily living (ADL) for stroke patients are limited. This systematic review and meta-analysis aimed to investigate the effect and safety of cerebellar TMS on balance capacity and ADL in stroke patients. Method A systematic search of seven electronic databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang and Chinese Scientific Journal) were conducted from their inception to October 20, 2023. The randomized controlled trials (RCTs) of cerebellar TMS on balance capacity and/or ADL in stroke patients were enrolled. The quality of included studies were assessed by Physiotherapy Evidence Database (PEDro) scale. Results A total of 13 studies involving 542 participants were eligible. The pooled results from 8 studies with 357 participants showed that cerebellar TMS could significantly improve the post-intervention Berg balance scale (BBS) score (MD = 4.24, 95%CI = 2.19 to 6.29, P

Effects of B4C on the microstructure and properties of Mg94Zn2.5Y2.5Mn1 alloy were investigated by means of optical microscope, scanning electron microscope, X-ray diffraction, transmission electron microscope, nano indentation tester and electronic universal testing machine. The results indicated that the as-cast Mg94Zn2.5Y2.5Mn1 alloy was mainly composed of α-Mg, fishbone-like W phase, and block 18 R long period stacking ordered (LPSO) phase. The addition of an appropriate amount of B4C could effectively refine grains, promote the formation of the LPSO phase and inhibit the generation of the W phase. The microstructure and mechanical properties of the alloy were both optimal at the addition of 0.5 at.% B4C. The microstructure exhibited a refined grain size from 41.2 μm to 20.7 μm, and the volume fraction of the LPSO phase increased from 8.1 % to 22.5 %. The yield strength increases from 112 MPa to 145 MPa, the tensile strength of the alloy was enhanced from 192 MPa to 256 MPa, and the elongation increased from 4.8 % to 8.6 %.

During malignant tumour development, the extracellular matrix (ECM) is usually abnormally regulated. Dysregulated expression of lysyl oxidase‐like 2 (LOXL2), matrix metalloproteinase 9 (MMP9) and lipocalin 2 (LCN2) are associated with ECM remodelling. In this study, protein–protein interaction assays indicated that LCN2 and LOXL2 interactions and LCN2 and MMP9 interactions occurred both intracellularly and extracellularly, but interactions between LOXL2 and MMP9 only occurred intracellularly. The LCN2/LOXL2/MMP9 ternary complex promoted migration and invasion of oesophageal squamous cell carcinoma (ESCC) cells, as well as tumour growth and malignant progression in vivo, while the iron chelator deferoxamine mesylate (DFOM) inhibited ESCC tumour growth. Co‐overexpression of LCN2, LOXL2 and MMP9 enhanced the ability of tumour cells to degrade fibronectin and Matrigel, increased the formation and extension of filopodia, and promoted the rearrangement of microfilaments through upregulation of profilin 1. In addition, the LCN2/LOXL2/MMP9 ternary complex promoted the expression of testican‐1 (SPOCK1), and abnormally activated the FAK/AKT/GSK3β signalling pathway. In summary, the LCN2/LOXL2/MMP9 ternary complex promoted the migration and invasion of cancer cells and malignant tumour progression through multiple mechanisms and could be a potential therapeutic target.

Abstract Glioblastoma is the most common type of brain tumor. Due to the presence of the blood-brain barrier, the effects of chemotherapy have been unsatisfactory. The combination of focused ultrasound and microbubbles to reversibly open the blood-brain barrier is now considered a key factor in improving treatment outcomes of glioblastoma. In this study, we developed bionic drug delivery microbubbles, which in combination with focused ultrasound had an obvious inhibitory effect on glioblastoma. We extracted the brain microvascular cell membranes, combined them with lipid components, and loaded them with superparamagnetic iron oxide and doxorubicin to prepare biomimetic drug delivery microbubbles (FeDOX@cellMBs). We demonstrated that FeDOX@cellMBs retained the intrinsic properties of loading, such as magnetic properties and drug toxicity, both in vitro and in vivo. FeDOX@cellMBs exhibited good tumor targeting and uptake under the combined action of magnetic and focused ultrasound. Importantly, the FeDOX@cellMBs demonstrated excellent internal stability and effectively inhibited tumor growth in orthotopic glioblastoma mice. Finally, organ H&E staining confirmed that FeDOX@cellMBs were safe for use. In conclusion, FeDOX@cellMBs successfully penetrated the blood-brain barrier and effectively inhibited glioblastoma growth under the combined effects of focused ultrasound and magnetic stimulation. These results provide a new approach for the treatment of glioblastoma, with implications for future clinical translation.

Abstract In order to explore the mapping recognition of arc welding molten pool characterisation and penetration state, according to the idea of embedded system construction, this article adopts the idea of software and hardware co‐design to find the zero‐crossing point of the second derivative in welding image edge detection, and give a threshold. When the absolute value of the first‐order derivative exceeds the threshold and has a different sign with the first‐order derivative of the previous edge, it is judged as a valid edge. The welding current adopts a symmetrical pulsed AC square wave, and the proportion of heat flow input is high. At the base current, the arc light is darker, so a clear image is obtained. This article designs a simulation experiment to verify the effect of the embedded system in this article. From the experimental research, it can be known that the embedded system constructed in this article can play a certain role in the mapping recognition of the arc welding molten pool characterisation and penetration state.

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10−15 g/L, and the quantitative limit reached 1.0 × 10−13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (KD) of 5.701 × 10−11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a KD of up to 4.181 × 10−10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate Cpk integrated Bootstrap-t. The Cpk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.

In this paper, the lateral Schottky barrier diodes (SBDs) with small capacitance and low turn-on voltage (Von) were fabricated on n-GaN and AlGaN/GaN heterostructure. The capacitances of lateral n-GaN SBD and lateral AlGaN/GaN SBD are 1.35 pF/mm and 0.70 pF/mm, respectively. Compared with the planar SBDs, the capacitances of lateral SBDs are reduced by about two orders of magnitude without sacrificing the performance of on-resistance (Ron) and reverse leakage current. For the planar and lateral n-GaN SBDs, the value of the Von is similar. However, compared with the planar AlGaN/GaN SBD, the Von of lateral AlGaN/GaN SBD is reduced from 1.64 V to 0.87 V owing to the anode metal directly contacting the two-dimensional electron gas. According to temperature-dependent I-V results, the barrier inhomogeneity of the lateral SBD is more intensive than the planar SBD, which is attributed to etching damage. The withstand voltage of SBD is a very important parameter for power electronic applications. Compared with the breakdown voltage of 73 V in the lateral n-GaN SBD, the lateral AlGaN/GaN SBDs exhibit a breakdown voltage of 2322 V. In addition, we found that Schottky contact introduces anode resistance (RA) by analysing the Ron distribution of lateral SBDs. The experimental results also show that the RA of lateral n-GaN SBD and lateral AlGaN/GaN SBD are 10.5 Ω mm and 9.2 Ω mm respectively, which are much larger than the ohmic contact resistance due to worsening anode contact by metal-induced gap states.

The wheel of high-speed trains requires high strength and hardness while imposing high demands on plasticity and toughness, resulting from the needs of working conditions. The fracture toughness KQ, as an important indicator of dynamics, often varies in the wheel, which affects the overall performance of the wheel. This work performs tests and analyses on typical samples with large fracture differences in fracture toughness at the same position and uniformly distributed on the same wheel. The mechanism of fracture toughness fluctuation is investigated, and the factors affecting fracture toughness are identified. The test mainly focuses on macroperformance, microfracture morphology, inclusion category and shape influence, pearlite lamellar spacing, and pearlite block size. Optical microscopy (OM), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), electron backscatter diffraction (EBSD), and quantitative metallographic technology were employed to investigate the mechanism and influence factors on fracture toughness fluctuation. The analysis shows that the width of the ductile laceration zone is directly correlated with the toughness, and the toughness level is influenced by the cleavage size, pearlite lamellar spacing, and pearlite block uniformity.

It is very important to monitor pH values. In this paper, we fabricated an all-solid-state AlGaN/GaN-based ion-sensitive heterostructure field effect transistor (ISHFET) pH sensor microprobe. The microprobe could facilitate measurement of pH values. The microprobe was fabricated by packaging the pH sensor microprobe chip into a 21 G medical needle. The performance of the integrated pH sensor microprobe was evaluated in pH range of 4–9.18. A sensitivity of 143.57 µA/pH can be achieved using the pH sensor microprobe with a width to length ratio of 4.2 at a drain–source voltage of 0.5 V. The pH sensor microprobe keeps a similar current when the pH values of solutions are the same. A response time of 1 s can be achieved when no neutralization reaction occurs. The pH sensor microprobe can accurately measure pH of solutions under 0.1M interfering ions. This probe-type AlGaN/GaN-based ISHFET pH sensor may be used in medicine or biology, especially in the detection of pH of biological fluid, blood, and some precious biological samples.

Human epidermal growth factor receptor-3 (HER-3) plays a key role in the growth and metastasis of cancer cells. The detection of HER-3 is very important for early screening and treatment of cancer. The AlGaN/GaN-based ion-sensitive heterostructure field effect transistor (ISHFET) is sensitive to surface charges. This makes it a promising candidate for the detection of HER-3. In this paper, we developed a biosensor for the detection of HER-3 with AlGaN/GaN-based ISHFET. The AlGaN/GaN-based ISHFET biosensor exhibits a sensitivity of 0.53 ± 0.04 mA/dec in 0.01 M phosphate buffer saline (1× PBS) (pH = 7.4) solution with 4% bovine serum albumin (BSA) at a source and drain voltage of 2 V. The detection limit is 2 ng/mL. A higher sensitivity (2.20 ± 0.15 mA/dec) can be achieved in 1× PBS buffer solution at a source and drain voltage of 2 V. The AlGaN/GaN-based ISHFET biosensor can be used for micro-liter (5 μL) solution measurements and the measurement can be performed after incubation of 5 min.

Due to the large difference in physical and chemical properties between the substrate and the cladding material, the welding of composite materials is much more difficult than that of single materials. In our work, S32304/Q390C composite material was considered as the research object. By adjusting the welding parameters, two kinds of joint geometry were obtained, namely, the transition layer weld lower (joint A) and higher the composite material interface (joint B). We studied the influence of the transition layer weld on the microstructure and properties of welded joints. The microstructure of the transition layer weld, the distribution of elements, the Schmidt factor of the interface between the transition layer and base layer weld, and the tensile strength of the joint were evaluated. The results show that with the increase of welding heat input, the microstructure of the transition layer weld changes from austenite and skeleton ferrite to austenite and lathy ferrite and austenite and acicular ferrite, while ferrite grows towards the weld center, showing a dendritic shape and a local network structure. At the side of the base layer weld of the interface between the transition and the base layer weld, the thickness of the low-carbon-content layer increased from 100 μm to 150 μm. Iron, chromium, and nickel elements on both sides of the interface were diffused, and the thickness of the diffusion layer increased from 3 μm to 10 μm. The tensile strength values of joints A and B were 648 MPa and 668 MPa, respectively, and the Schmidt factor values were 0.446 and 0.454, respectively. Combination with the analysis of the fracture morphology showed that when the transition layer weld was higher than the interface of the composite plate, the joint had better plastic deformation ability and higher tensile strength.

Context Re-yan-ning mixture (RYNM) is a new national drug approved by China's State Food and Drug Administration for the treatment of colds, simple pneumonia and acute bronchitis. Objective To determine the mechanism of action of RYNM in the treatment of bacterial pneumonia. Materials and methods Using the network pharmacology approach, the multiple components, component candidate targets and multiple therapeutic targets of RYNM were screened and functionally enriched. Also, we established a rat Streptococcus pneumonia model to verify the results of network pharmacology enrichment analysis. Forty male SPF Sprague Dawley rats were divided into four groups of 10 rats: control (normal saline), model (normal saline), levofloxacin-intervened and RYNM-intervened groups. IL-10, NOS2, COX-1, IL-6, TNF-α and NF-κB in serum and BALF were detected by ELISA. Western blot detected IL-17, IL-6, TNF-α, COX-2 and Bcl-2. Results The network pharmacology approach successfully identified 48 bioactive components in RYNM, and 65 potential targets and 138 signal pathways involved in the treatment of Streptococcus pneumonia with RYNM. The in vivo experiments indicated that model group has visible inflammation and lesions while RYNM and levofloxacin groups have not. The RYNM exhibited its therapeutic effects on Streptococcus pneumonia mainly via the regulation of cell proliferation and survival through the IL-6/IL-10/IL-17, Bax/Bcl-2, COX-1/COX-2, NF-κB and TNF-α signalling pathways. Discussion and conclusions The present study demonstrated the protective effects of RYNM on Streptococcus pneumonia, providing a potential mechanism for the treatment of bacterial pneumonia with RYNM.

The AlGaN/GaN Schottky barrier diodes (SBDs) working as high-power mixer and multiplier show great potential in millimeter wave (MMW) field owing to their high breakdown voltage. Nevertheless, its further application is severely limited by large reverse leakage current (Jr) since the two-dimensional electron gas (2DEG) channel is hard to be pinched off at low voltage. To address this limitation, a graded AlGaN/GaN heterostructure is introduced to extend the 2DEG channel into a quasi-three-dimensional electron slab. By comparing the fixed Al composition AlGaN/GaN SBD, Jr of the graded AlGaN/GaN SBD is significantly reduced due to the extension of channel carriers, confirming the effective Jr suppression effect of this structure. Furthermore, on this basis, a recessed anode structure is utilized to expect a smaller Jr. The results indicated that the graded AlGaN/GaN SBDs with air-bridge structure have achieved a pretty low Jr value (1.6 × 10−13 A at -15 V), and its cutoff frequency is as high as 60.6 GHz. It is expected that such SBDs with low Jr have significant advantages in future applications.

TIG arc additive manufacturing experiments were performed utilizing TiB2 nanoparticle-reinforced toward to 7075 aluminum alloy welding wire, and the microstructure and mechanical properties corresponding to different locations of welding plate were investigated. At the top location of the deposited layer, the microstructure was characterized by fine dendrite induced by solidification, and equiaxed grain was predominant at the middle location. The grain size at the bottom location was obviously larger compared to the top and middle locations, and secondary-phase particles were homogeneously distributed at the grain boundary or inner grains. The mechanical properties at the top location of the deposited layer were most excellent compared to the middle and bottom locations, and the tensile properties and micro-hardness were decreased with the detected area varying from middle location to the bottom location. The excellent combination of fracture elongation and maximum of tensile strength corresponding to different locations on the deposited layer were determined to be 361.8 MPa with respect to the 7075 aluminum alloy welding wire, respectively, which was higher compared to the samples processed by general arc additive manufacturing process with tensile strength of (279.4 ± 5.3) MPa, indicating the TiB2 nano-sized particles possessed certain enhancing effects on the investigated 7075 aluminum alloy.

Glioma is the most common type of malignant tumor in the central nervous system with an unfavorable prognosis and limited treatment. In this study, we are devoted to addressing the prognostic value of DNA damage repair-related genes in low-grade glioma (LGG). We plotted the landscape of DNA damage repair (DDR)-related genes and identified SMC4 as an independent prognostic marker with integrated bioinformatics analysis, which is overexpressed in different histologic subtypes of glioma. We observed that SMC4 expression is elevated in recurrent LGG patients or those with advanced histologic staging. SMC4 depletion inhibits proliferation and induces increased replication damage in LGG cells. Lastly, we predicted and validated the transcription modulation of SMC4 by a transcription factor, MYB, at the -976bp~ -837bp of the SMC4 promoter region in LGG cells. Together, our study identified SMC4 as a potential prognostic biomarker for LGG patients, which functions to promote cell proliferation by repairing replication damage and the expression of SMC4 could be transcriptionally regulated by MYB.

In this paper, in situ SiC-reinforced Al-Zn-Mg-Cu composites were fabricated by laser powder bed fusion (LPBF). The effects of SiC content on the microstructure, phase composition, microhardness, and wear resistance of as-printed composites were preliminarily investigated. Results show that the microstructure was regulated, the matrix grains were refined, and the tendency to orientation grain growth was suppressed. SiC particles reacted in situ with the Al matrix to produce Si, Al4C3, and Al4SiC4 phases. The microhardness and wear resistance of as-printed composites increased with SiC content due to the fine grain strengthening of the matrix and the second phase strengthening of precipitates and reinforcements.

Optrodes, which are single shaft neural probes integrated with microelectrodes and optical light sources, offer a remarkable opportunity to simultaneously record and modulate neural activities using light within an animal’s brain; however, a common problem with optrodes is that stimulation artifacts can be observed in the neural recordings of microelectrodes when the light source on the optrode is activated. These stimulation artifacts are undesirable contaminants, and they cause interpretation complexity when analyzing the recorded neural activities. In this paper, we tried to mitigate the effects of the stimulation artifacts by developing a low-noise, double-sided optrode integrated with multiple Electromagnetic Shielding (EMS) layers. The LED and microelectrodes were constructed separately on the top epitaxial and bottom substrate layers, and EMS layers were used to separate the microelectrodes and LED to reduce signal cross-talks. Compared with conventional single-sided designs, in which the LED and microelectrodes are constructed on the same side, our results indicate that double-sided optrodes can significantly reduce the presence of stimulation artifacts. In addition, the presence of stimulation artifacts can further be reduced by decreasing the voltage difference and increasing the rise/fall time of the driving LED pulsed voltage. With all these strategies, the presence of stimulation artifacts was significantly reduced by ~76%. As well as stimulation suppression, the sapphire substrate also provided strong mechanical stiffness and support to the optrodes, as well as improved electronic stability, thus making the double-sided sapphire optrodes highly suitable for optogenetic neuroscience research on animal models.

Magnetic pulse welding (MPW) is widely used in the connection of dissimilar metals. The welding process involves the coupling of the electromagnetic field and structural field, which is a high-energy transient forming process. Based on the current experimental methods, it is difficult to capture the relevant data in the process of magnetic pulse welding, and the transient forming mechanism of magnetic pulse welding needs to be further studied. Taking the magnetic pulse welding of an Al-Mg sheet as an example, based on the Ansoft Maxwell and ANSYS finite element simulation platform, the loose coupling method was used to analyze an electromagnetic field generated by the discharging capacitor bank and structural field of the Al-Mg sheet under the action of electromagnetic force. The discharge period of the magnetic pulse welding capacitor bank was 62 μs. The current direction in the aluminum sheet changed once half a cycle, and the direction of the electromagnetic force was always consistent with the Z-axis. Under the skin effect, the magnetic induction intensity on the lower surface of the aluminum sheet was the largest. At 16 μs, the induced current, electromagnetic force and magnetic induction intensity in the aluminum sheet reached the peak values, which were 7.89 A/m2, 4.58 N/m3 and 12.6 T, respectively. The maximum electromagnetic force and velocity in the structural field were 2400 KN and 300 m/s. The structure field simulation reproduces the transient forming process of magnetic pulse welding, and clarifies the formation mechanism of the “intermediate zone rebound uncomposite zone-welding bonding zone-unbound zone”. Based on the numerical simulation technology, the research on the transient forming mechanism of magnetic pulse welding under multiphysics simulations can promote the development and application of magnetic pulse welding technology and better guide engineering practices.

Traditional GaAs-based frequency multipliers still exhibit great challenges to meet the demand for solid-state high-power THz sources due to low breakdown voltage and heat dissipation of the Schottky barrier diode (SBD). In this study, a GaN SBD chain was fabricated with n−/n+-GaN structure. As a consequence, the breakdown voltage of 54.9 V at 1 μA and cut-off frequency of 587.5 GHz at zero bias were obtained. A 120 GHz frequency-doubler module based on the GaN SBD chain was designed and fabricated. When driven with 500 mW input power in a continuous wave, the output power of the frequency-doubler module was 15.1 mW at 120 GHz. Moreover, the experiments show that the frequency-doubler module can endure an input power of 2 W. In addition, it is worth noting that the SBD chain works well at an anode temperature of 337.2 °C.

Micropyramid vertical GaN-based ultraviolet (UV) light-emitting diodes (LEDs) on Si(111) substrate have been fabricated by selective area growth to reduce threading dislocations and the polarization effects. There is no-light emission at the bottom and six planes of the pyramid at lower current due to the leakage current and nonradiative recombination of the dislocation at the bottom and the 90° threading dislocations (TDs) at six planes of the pyramid, and the top of the pyramid is the high-brightness region. The micropyramid UV LED has a high optical output intensity under a small current injection, and the series resistance of unit area is only a quarter of the conventional vertical LEDs, so the micropyramid UV LED would have a high output power under the drive circuit. The reverse leakage current of a single micropyramid UV LED is 2 nA at −10 V.

Human herpesvirus 6 (HHV-6) is an important immunosuppressive and immunomodulatory virus worldwide. However, whether and how HHV-6 infection influences the metabolic machinery of the host cell to provide the energy and biosynthetic resources for virus propagation remains unknown. In this study, we identified that HHV-6A infection promotes glucose metabolism in infected T cells, resulting in elevated glycolytic activity with an increase of glucose uptake, glucose consumption and lactate secretion. Furthermore, we explored the mechanisms involved in HHV-6A-mediated glycolytic activation in the infected T cells. We found increased expressions of the key glucose transporters and glycolytic enzymes in HHV-6A-infected T cells. In addition, HHV-6A infection dramatically activated AKT-mTORC1 signaling in the infected T cells and pharmacological inhibition of mTORC1 blocked HHV-6A-mediated glycolytic activation. We also found that direct inhibition of glycolysis by 2-Deoxy-D-glucose (2-DG) or inhibition of mTORC1 activity in HHV-6A-infected T cells effectively reduced HHV-6 DNA replication, protein synthesis and virion production. These results not only reveal the mechanism of how HHV-6 infection affects host cell metabolism, but also suggest that targeting the metabolic pathway could be a new avenue for HHV-6 therapy.

The capacitance and the series resistance are two main factors which determine the cut-off frequency of Schottky barrier diodes (SBDs) for their application in millimeter-wave and terahertz regions. The junction capacitance is closely related to the anode dimension of a SBD. Reducing the anode size can effectively decrease the junction capacitance, but it will increase the series resistance and the difficulty of the device manufacturing process is also increased. In this paper, an AlGaN/GaN based air-bridge structure planar SBD with a half through-hole is investigated. The half through-hole was formed on the center of a circular anode by inductively coupled plasma etching to the unintentional doping-GaN channel layer. The capacitance formed by the anode metal and the two-dimensional electron gas at the AlGaN/GaN interface is effectively reduced under the condition of holding the metal area of anode. The total capacitance of the 20 μm-radius anode SBD with a 19.95 μm-radius half through-hole dramatically decreases from 2.32 pF of the device without the half through-hole to 21.5 fF. In addition, since the current is mainly distributed at the edge of the circular anode, the series resistance is only slightly increased. The cut-off frequency of the air-bridge planar SBD with a 20 μm-radius anode and a 19.95 μm-radius half through-hole was 114.1 GHz. To reduce the size of the anode and optimize the ohmic contact, the cut-off frequency could be further improved.

Based on the thermodynamic conversion mechanism and energy transition principle, a three-dimensional cellular automata model of grain growth is established from the aspects of grain orientation, grain size distribution, grain growth kinetics, and grain topology. Also, the effect of temperature on the three-dimensional grain growth process of AZ31 magnesium alloy is analyzed. The results show that the normal growth of three-dimensional grains satisfies the Aboav-weaire equation, the average number of grain planes is between 12 and 14 at 420°C and 2000 CAS, and the maximum number of grain planes is more than 40. Grains of different sizes are distributed normally at different times, most of which are grains with the ratio of grain diameter to average grain diameter R/Rm ≈ 1.0, which meets the minimum energy criterion of grain evolution. The grain of AZ31 magnesium alloy increases in size with the increase of temperature, and the number of grains decreases with the increase in time. The angle between the two-dimensional slices of three-dimensional grains is approximately 120°, which is consistent with that of the traditional two-dimensional cellular automata. The relative error of grain size before and after heat preservation is in the range of 0.1–0.6 μm, which indicates that the 3D cellular automata can accurately simulate the heat preservation process of AZ31 magnesium alloy.

Objective: A novel processing analytical framework of Chinese Material Medica (CMM) includes breeding process analysis, planting process analysis, producing process analysis and manufacture process analysis. In order to study this framework, we used quality control of honeysuckle flower (Lonicerae japonicae Flos) including diploid and tetraploid Lonicera japonica, and wild honeysuckle flower (Lonicerae Flos) including Lonicerae hypoglauca, Lonicerae confusa, Lonicerae fulvotomentosa and Lonicerae macranthoides as an example. Methods: A total of 360 samples were analyzed from three variables including species, growing areas, and optimization of processing methods. For quantitative analysis, chlorogenic acid (CA), isochlorogenic acid A (3, 5-DCA), and isochlorogenic acid C (4, 5-DCA) were measured with high performance liquid chromatography (HPLC). Results: The three organic acids contents are higher in wild honeysuckle flower than honeysuckle flower; L. japonica (tetraploid) is higher than L. japonica (diploid). Modern processing methods (kill-enzyme torrefaction and fixing machine drying) are popular in growing areas and are superior to traditional methods (sun and shade drying). Conclusions: Novel process analysis concepts in processing analytical technology (PAT) enriched the Chinese Material Medica contents. Keywords: Honeysuckle flower, Wild honeysuckle flower, Processing analytical technology, Quality control, Processing method

Integrated optrodes for optogenetics have been becoming a significant tool in neuroscience through the combination of offering accurate stimulation to target cells and recording biological signals simultaneously. This makes it not just be widely used in neuroscience researches, but also have a great potential to be employed in future treatments in clinical neurological diseases. To optimize the integrated optrodes, this paper aimed to investigate the influence of surface material and illumination upon the performance of the microelectrode/electrolyte interface and build a corresponding evaluation system. In this work, an integrated planar optrode with a blue LED and microelectrodes was designed and fabricated. The charge transfer mechanism on the interface was theoretically modeled and experimentally verified. An evaluation system for assessing microelectrodes was also built up. Using this system, the proposed model of various biocompatible surface materials on microelectrodes was further investigated under different illumination conditions. The influence of illumination on the microelectrode/electrolyte interface was the cause of optical artifacts, which interfere the biological signal recording. It was found that surface materials had a great effect on the charge transfer capacity, electrical stability and recoverability, photostability, and especially optical artifacts. The metal with better charge transfer capacity and electrical stability is highly possible to have a better performance on the optical artifacts, regardless of its electrical recoverability and photostability under the illumination conditions of optogenetics. Among the five metals used in our investigation, iridium served as the best surface material for the proposed integrated optrodes. Thus, optimizing the surface material for optrodes could reduce optical interference, enhance the quality of the neural signal recording for optogenetics, and thus help to advance the research in neuroscience.

New sensor technologies play an important role in quality evaluation of Chinese materia medica (CMM) and include near-infrared spectroscopy, chemical imaging, electronic nose and electronic tongue. This review on quality evaluation of CMM and the application of the new sensors in this assessment is based on studies from 2010 to 2015, with prospects and opportunities for future research.

Ion-sensitive field effect transistor (ISFET) has been widely used as a pH sensor. Its sensitivity can be expressed in terms of current or voltage which were defined by us as SA and SV in this article. Using current to represent sensitivity is more convenient for it can simplify the subsequent circuits. What’s more, SA contains more information including the geometry of the device, the parameter of the epitaxial material and the property of the sensitive membrane while SV only contains the information of the sensitive membrane, which helps us to analyze the device performance. In this paper, the sensitivity SA was deduced theoretically based on the previous research and was verified experimentally. On this basis, we put forward a method that can separate the effect of the sensitive membrane on the sensitivity from the material completely by designing a series of AlGaN/GaN based heterostructure ISFET pH sensors with different sizes of the channel area (width/length parameter). Experimental result shows the importance of this method in the future research.

Objective: Rapid discrimination of three classes of safflowers, dyed safflower, adulterated safflower, and pure safflower using computer vision and image processing algorithms. Methods: A low cost computer vision system (CVS) was designed to measure the color of safflowers in the RGB (red, green, blue), L∗a∗b∗, and HSV (hue, saturation, vale) color spaces. The color moments in these three color spaces were extracted from the acquired images as color features of safflower. In addition, five kinds of pigments that are commonly used to dye safflowers were identified by high-performance liquid chromatography as a reference. Pattern recognition methods were investigated for rapid discrimination, including an unsupervised principal component analysis (PCA) algorithm and a supervised partial least squares discriminant analysis (PLS-DA) algorithm. Results: The mean error (e¯) between color values measured with the colorimeter and calculated with the CVS was 2.4%, with a high correlation coefficient (r) of 0.9905. This result indicated that the established CVS was reliable for color estimation of safflowers. The PLS-DA model, which had a total accuracy of 91.89%, outperformed the PCA model in classifying pure, adulterated, and dyed safflowers. Conclusion: The color objectification is a promising tool for rapid identification of dyed and adulterated safflowers.

Objective: In this study, safflower (Carthamus tinctorius L.) was taken as a representative example to examine the application of color characteristics to evaluate quality. Methods: A computer vision system was established for the objective and nondestructive assessment of color using image processing algorithms. Color parameters were investigated based on the RGB, L*a*b and HSV color spaces. The content of hydroxysafflor yellow A (HSYA), a major bioactive constituent of safflower, was determined by high-performance liquid chromatography. The relationship between HSYA content and color values was investigated by Pearson correlation analysis. A multiple linear regression model was established to predict the HSYA content from color values. Results: The red color and lightness of safflower were found to be significantly related to HSYA content. The prediction equation obtained by multiple regression was reliable with an R2 value of 0.805 (P < .01). Conclusion: The results suggest that the computer vision technique could be used as a promising and non-destructive technology for color measurement and quality evaluation of CHM.

Our work proved that processing trajectory could effectively obtain a more reliable and robust quantitative model compared with the step-by-step optimization method. The use of systematic tracking was investigated as a tool to optimize modeling parameters including calibration method, spectral pretreatment and variable selection latent factors. The variable was selected by interval partial least-squares (iPLS), backward interval partial least-square (BiPLS) and synergy interval partial least-squares (SiPLS). The models were established by Partial least squares (PLS) and Bagging-PLS. The model performance was assessed by using the root mean square errors of validation (RMSEP) and the ratio of standard error of prediction to standard deviation (RPD). The proposed procedure was used to develop the models for near infrared (NIR) datasets of active pharmaceutical ingredients in tablets and chlorogenic acid of Lonicera japonica solution in ethanol precipitation process. The results demonstrated the processing trajectory has great advantages and feasibility in the development and optimization of multivariate calibration models as well as the effectiveness of bagging model and variable selection to improve prediction accuracy and robustness.

Particle size is of great importance for the quantitative model of the NIR diffuse reflectance. In this paper, the effect of sample particle size on the measurement of harpagoside in Radix Scrophulariae powder by near infrared diffuse (NIR) reflectance spectroscopy was explored. High-performance liquid chromatography (HPLC) was employed as a reference method to construct the quantitative particle size model. Several spectral preprocessing methods were compared, and particle size models obtained by different preprocessing methods for establishing the partial least-squares (PLS) models of harpagoside. Data showed that the particle size distribution of 125–150 μm for Radix Scrophulariae exhibited the best prediction ability with Rpre2 = 0.9513, RMSEP = 0.1029 mg·g−1, and RPD = 4.78. For the hybrid granularity calibration model, the particle size distribution of 90–180 μm exhibited the best prediction ability with Rpre2 = 0.8919, RMSEP = 0.1632 mg·g−1, and RPD = 3.09. Furthermore, the Kubelka-Munk theory was used to relate the absorption coefficient k (concentration-dependent) and scatter coefficient s (particle size-dependent). The scatter coefficient s was calculated based on the Kubelka-Munk theory to study the changes of s after being mathematically preprocessed. A linear relationship was observed between k/s and absorption A within a certain range and the value for k/s was >4. According to this relationship, the model was more accurately constructed with the particle size distribution of 90–180 μm when s was kept constant or in a small linear region. This region provided a good reference for the linear modeling of diffuse reflectance spectroscopy. To establish a diffuse reflectance NIR model, further accurate assessment should be obtained in advance for a precise linear model.

Model performance of the partial least squares method (PLS) alone and bagging-PLS was investigated in online near-infrared (NIR) sensor monitoring of pilot-scale extraction process in Fructus aurantii. High-performance liquid chromatography (HPLC) was used as a reference method to identify the active pharmaceutical ingredients: naringin, hesperidin and neohesperidin. Several preprocessing methods and synergy interval partial least squares (SiPLS) and moving window partial least squares (MWPLS) variable selection methods were compared. Single quantification models (PLS) and ensemble methods combined with partial least squares (bagging-PLS) were developed for quantitative analysis of naringin, hesperidin and neohesperidin. SiPLS was compared to SiPLS combined with bagging-PLS. Final results showed the root mean square error of prediction (RMSEP) of bagging-PLS to be lower than that of PLS regression alone. For this reason, an ensemble method of online NIR sensor is here proposed as a means of monitoring the pilot-scale extraction process in Fructus aurantii, which may also constitute a suitable strategy for online NIR monitoring of CHM.

Laser-induced breakdown spectroscopy (LIBS) was applied to perform a rapid elemental analysis and provenance study of Blumea balsamifera DC. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were implemented to exploit the multivariate nature of the LIBS data. Scores and loadings of computed principal components visually illustrated the differing spectral data. The PLS-DA algorithm showed good classification performance. The PLS-DA model using complete spectra as input variables had similar discrimination performance to using selected spectral lines as input variables. The down-selection of spectral lines was specifically focused on the major elements of B. balsamifera samples. Results indicated that LIBS could be used to rapidly analyze elements and to perform provenance study of B. balsamifera.

Near infrared chemical imaging (NIR-CI) combines conventional near infrared (NIR) spectroscopy with chemical imaging, thus provides spectral and spatial information simultaneously. It could be utilized to visualize the spatial distribution of the ingredients in a sample. The data acquired using NIR-CI instrument are hyperspectral data cube (hypercube) containing thousands of spectra. Chemometric methodologies are necessary to transform spectral information into chemical information. Partial least squares (PLS) method was performed to extract chemical information of chlorpheniramine maleate in pharmaceutical formulations. A series of samples which consisted of different CPM concentrations (w/w) were compressed and hypercube data were measured. The spectra extracted from the hypercube were used to establish the PLS model of CPM. The results of the model were Rval2 0.981, RMSEC 0.384%, RMSECV 0.483%, RMSEP 0.631%, indicating that this model was reliable.

The present study aimed at investigating the relationship between tablet hardness and homogeneity of different Yinhuang dispersible tablets by near-infrared chemical imaging (NIR-CI) technology. The regularity of best hardness was founded between tablet hardness and the spatial distribution uniformity of Yinhuang dispersible tablets. The ingredients homogeneity of Yinhuang dispersible tablets could be spatially determined using basic analysis of correlation between analysis (BACRA) method and binary image. Then different hardnesses of Yinhuang dispersible tablets were measured. Finally, the regularity between tablet hardness and the spatial distribution uniformity of Yinhuang dispersible tablets was illuminated by quantifying the agglomerate of polyvinyl poly pyrrolidone (PVPP). The result demonstrated that the distribution of PVPP was unstable when the hardness was too large or too small, while the agglomerate of PVPP was smaller and more stable when the best tablet hardness was 75N. This paper provided a novel methodology for selecting the best hardness in the tabletting process of Chinese Medicine Tablet.

Deoxyschizandrin (DS) is a bioactive benzocyclooctadiene lignan found in the fruit of Schisandra chinensis. However, poor bioavailability and non-specificity of DS frequently caused low therapeutic efficacy. In the present study, DS-liposome (DS-lipo) was implemented to enhance the hepatic targeting and inhibition effects on adipocyte differentiation in 3T3-L1 cells. The formulations enabled encapsulation of as much as 24.14% DS. The DS-lipo prepared was about 73.08 nm, as measured by laser light scattering (LLS) morphology. In the visual field of a scanning electron microscope (SEM), the liposomes were spherical with similar size and uniform dispersion. Fluorescence live imaging study exhibited hepatic targeting of liposomes in vivo. Furthermore, High-Content Analysis (HCS) imaging microassay analyses revealed DS-lipo and DS reduced cytoplasmic lipid droplet in 3T3-L1 adipocytes, with the IC50 value of 8.68 μM and 31.08 μM, respectively. The lipid droplet accumulation inhibition rate of 10 μM DS-lipo was above 90%, which was even superior to the effect of 30 μM DS solution. The current findings suggest that DS-lipo was a therapeutic strategy for alleviating lipid-associated diseases and nonalcoholic fatty liver disease (NAFLD).

Near infrared (NIR) assignment of Isopsoralen was performed using deuterated chloroform solvent and two-dimensional correlation spectroscopy (2D-COS) technology. Yunkang Oral Liquid was applied to study Isopsoralen, the characteristic bands by spectral assignment as well as the bands by interval partial least squares (iPLS) and synergy interval partial least squares (siPLS) were used to establish partial least squares (PLS) model. The coefficient of determination in calibration $(R_{\rm cal}^{2})$ were 0.9987, 0.9970 and 0.9982. The coefficient of determination in cross validation $(R_{\rm val}^{2})$ were 0.9985, 0.9921 and 0.9982. The coefficient of determination in prediction $(R_{\rm pre}^{2})$ were 0.9987, 0.9955 and 0.9988. The root mean square error of calibration (RMSEC) were 0.27, 0.40 and 0.31 ppm. The root mean square error of cross validation (RMSECV) were 0.30, 0.67 and 0.32 ppm. The root mean square error of prediction (RMSEP) were 0.23, 0.43 and 0.22 ppm. The residual predictive deviation (RPD) were 31.00, 16.58 and 32.41. It turned out that the characteristic bands by spectral assignment had the same results with the chemometrics methods in PLS model. It provided guidance for NIR spectral assignment of chemical compositions in Chinese Materia Medica (CMM).

In this work, multivariate detection limits (MDL) estimator was obtained based on the micro-electro-mechanical systems–near infrared (MEMS–NIR) technology coupled with two sampling accessories to assess the detection capability of four quality parameters (glycyrrhizic acid, liquiritin, liquiritigenin and isoliquiritin) in licorice from different geographical regions. 112 licorice samples were divided into two parts (calibration set and prediction set) using Kennard–Stone (KS) method. Four quality parameters were measured using high-performance liquid chromatography (HPLC) method according to Chinese pharmacopoeia and previous studies. The MEMS–NIR spectra were acquired from fiber optic probe (FOP) and integrating sphere, then the partial least squares (PLS) model was obtained using the optimum processing method. Chemometrics indicators have been utilized to assess the PLS model performance. Model assessment using chemometrics indicators is based on relative mean prediction error of all concentration levels, which indicated relatively low sensitivity for low-content analytes (below 1000 parts per million (ppm)). Therefore, MDL estimator was introduced with alpha error and beta error based on good prediction characteristic of low concentration levels. The result suggested that MEMS–NIR technology coupled with fiber optic probe (FOP) and integrating sphere was able to detect minor analytes. The result further demonstrated that integrating sphere mode (i.e., MDL0.05,0.05, 0.22%) was more robust than FOP mode (i.e., MDL0.05,0.05, 0.48%). In conclusion, this research proposed that MDL method was helpful to determine the detection capabilities of low-content analytes using MEMS–NIR technology and successful to compare two sampling accessories.

This study demonstrated particle size effect on the measurement of saikosaponin A in Bupleurum chinense DC. by near infrared reflectance (NIR) spectroscopy. Four types of granularity were prepared including powder samples passed through 40-mesh, 65-mesh, 80-mesh, and 100-mesh sieve. Effects of granularity on NIR spectra were investigated, which showed to be wavelength dependent. NIR intensity was proportional to particle size in the first combination-overtone and combination region. Local partial least squares model was constructed separately for every kind of samples, and data-preprocessing techniques were performed to optimize calibration model. The 65-mesh model exhibited the best prediction ability with root mean of square error of prediction (RMSEP) = 0.492 mg·g−1, correlation coefficient RP=0.9221, and relative predictive determinant (RPD) = 2.58. Furthermore, a granularity-hybrid calibration model was developed by incorporating granularity variation. Granularity-hybrid model showed better performance than local model. The model performance with 65-mesh samples was still the most accurate with RMSEP = 0.481 mg·g−1, RP=0.9279, and RPD = 2.64. All the results presented the guidance for construction of a robust model coupled with granularity-hybrid calibration set.

Friction stir welding (FSW) is well recognized as a very practical technology for joining magnesium alloys. Although, a large amount of progress have been made on the FSW of magnesium alloys, it should be emphasized that many challenges still remain in joining magnesium using FSW. In this article, we briefly review the background of friction stir welding of magnesium alloys, and then focus on the effects of the friction stir welding on the macrostructure, microstructure evolution, texture distribution, and the mechanical properties of the welding joints. The macro-defects in welds and their relationship to the welding parameters such as welding speed, rotation speed, and axial force were also discussed. The review concluded with some suggested methods improvement and future challenges related to FSW of magnesium alloys. The purpose of the present review paper is to fully understand the relationships between the microstructure and the properties, and then establish a global, state-of-the-art FSW of magnesium alloys.

In this paper, a 2D numerical model that is more physically realistic was established to simulate the complete process of Ti/Al explosive welding. Basing on the ANSYS/AUTODYN software package, the smoothed particle hydrodynamics (SPH) and arbitrary Lagrangian-Eulerian (ALE) were used for running this simulation. The numerical model can capture the typical physics in the explosive welding process, including the expansion of explosives, flyer plate bending, the impact of metal plates, jetting, and the wavy interface. The variable physical parameters during the explosive welding process were discussed. Most parts of the jet originated from the aluminum plate. According to the model, the jet velocity reached 7402 m/s. The pressure at the detonation point was too small to make the two plates to bond. The pressure could reach an order of magnitude of 107 kPa when the detonation energy tended to be stable and was far more than the yield strength of both materials, which resulted in an obvious narrow region of plastic strain emerging close to the collision zone. The signs of shear stresses between the two plates were the opposite. The interface morphology changed from straight to wave along the propagation of the detonation wave in the simulation, which was consistent with the experimental results.

A bimetal composite of 2205 duplex stainless steel and AZ31B magnesium alloy was cladded successfully through the method of explosive welding. The microstructural characteristics and mechanical properties of 2205/AZ31B bimetal composite are discussed. The interface of 2205/AZ31B bimetallic composite was a less regular wavy morphology with locally melted pockets. Adiabatic shear bands occurred only in the AZ31B side near explosive welding interface. The microstructure observed with EBSD showed a strong refinement near the interface zones. Line scan confirmed that the interface had a short element diffusion zone which would contribute to the metallurgical bonding between 2205 duplex stainless steel and AZ31B magnesium alloy. The value of micro-hardness near the bonding interface of composite plate increased because of work hardening and grain refinement. The tensile shear strength of bonding interface of 2205/AZ31B composite was 105.63 MPa. Tensile strength of 2205/AZ31B composite material was higher than the base AZ31B. There were two abrupt drops in stress in the stress–strain curves of the 2205/AZ31B composite materials.

This study demonstrated that near infrared chemical imaging (NIR-CI) was a rapid and nondestructive technique for discrimination of chlorpheniramine maleate (CPM) and assessment of its surface content uniformity (SCU) in a pharmaceutical formulation. The characteristic wavenumber method was used for discriminating CPM distribution on the tablet surface. To assess the surface content uniformity of CPM, binary image and statistical measurement were proposed. Furthermore, high-performance liquid chromatography (HPLC) was used as reference method for accurately determining volume content of CPM in the sample. Moreover, HPLC was performed to assess volume content uniformity (VCU) of CPM in whole region and part region of the tablets. The NIR-CI result showed that the spatial distribution of CPM was heterogeneous on the tablet surface. Through the comparison of content uniformity of CPM determined by NIR-CI and HPLC, respectively, it demonstrated that a high degree of VCU did not imply a high degree of SCU of the samples. These results indicate that HPLC method is not suitable for testing SCU, and this has been verified by NIR-CI. This study proves the feasibility of NIR-CI for rapid discrimination of CPM and assessment of its SCU, which is helpful for the quality control of commercial CPM tablets.