A High-Reliability RF MEMS Metal-Contact Switch Based on Al-Sc Alloy.

This paper presents a new metal-contact RF MEMS switch based on an Al-Sc alloy. The use of an Al-Sc alloy is intended to replace the traditional Au-Au contact, which can greatly improve the hardness of the contact, and thus improve the reliability of the switch. The multi-layer stack structure is adopted to achieve the low switch line resistance and hard contact surface. The polyimide sacrificial layer process is developed and optimized, and the RF switches are fabricated and tested for pull-in voltage, S-parameters, and switching time. The switch shows high isolation of more than 24 dB and a low insertion loss of less than 0.9 dB in the frequency range of 0.1-6 GHz.

Effects of Mask Material on Lateral Undercut of Silicon Dry Etching.

The silicon etching process is a core component of production in the semiconductor industry. Undercut is a nonideal effect in silicon dry etching. A reduced undercut is desired when preparing structures that demand a good sidewall morphology, while an enlarged undercut is conducive to the fabrication of microstructure tips. Undercut is related to not only the production parameters but also the mask materials. In this study, five mask materials-Cr, Al, ITO, SiNx, and SiO2-are chosen to compare the undercut effect caused by the isotropic etching process and the Bosch process. In the Bosch process, the SiNx mask causes the largest undercut, and the SiO2 mask causes the smallest undercut. In the isotropic process, the results are reversed. The effect of charges in the mask layer is found to produce this result, and the effect of electrons accumulating during the process is found to be negligible. The undercut effect can be enhanced or suppressed by selecting appropriate mask materials, which is helpful in the MEMS process. Finally, using an Al mask, a tapered silicon tip with a top diameter of 119.3 nm is fabricated using the isotropic etching process.

Long non-coding RNA SNHG15 regulates cardiomyocyte apoptosis after hypoxia/reperfusion injury via modulating miR-188-5p/PTEN axis.

Nowadays the most effective way to cure myocardial infarction (MI) is reperfusion, which inevitably leads to cardiomyocyte apoptosis. In this study, we discussed the functions of SNHG15 in regulating cardiomyocyte apoptosis through the modulation of miR-188-5p/PTEN axis. We examined the links between SNHG15 and miR-188-5p/PTEN in mice with MI. Extensive experiments, measurements and comparisons were performed, including RT-PCR, western blotting, luciferase reporter assay, flow cytometry analysis etc. Through a series of comparisons and analysis, we discovered that SNHG15 could interact with the miR-188-5p/PTEN axis and impact the cellular physiology of cardiomyocyte apoptosis. PTEN was upregulated in hypoxia cells, but this effect was attenuated by miR-188-5p. MiR-188-5p could combine with SNHG15 and PTEN, and form a SNHG15-miR-188-5p-PTEN axis, which regulated the apoptosis of MCs. These results suggest that LncRNA SNHG15 regulates cardiomyocyte apoptosis induced by hypoxia or reperfusion injury through modulating of miR-188-5p/PTEN axis.

Design and Fabrication of a Novel Poly-Si Microhotplate with Heat Compensation Structure.

I Microhotplates are critical devices in various MEMS sensors that could provide appropriate operating temperatures. In this paper, a novel design of poly-Si membrane microhotplates with a heat compensation structure was reported. The main objective of this work was to design and fabricate the poly-Si microhotplate, and the thermal and electrical performance of the microhotplates were also investigated. The poly-Si resistive heater was deposited by LPCVD, and phosphorous doping was applied by in situ doping process to reduce the resistance of poly-Si. In order to obtain a uniform temperature distribution, a series of S-shaped compensation structures were fabricated at the edge of the resistive heater. LPCVD SiNx layers deposited on both sides of poly-Si were used as both the mechanical supporting layer and the electrical isolation layer. The Pt electrode was fabricated on the top of the microhotplate for temperature detection. The area of the heating membrane was 1 mm × 1 mm. Various parameters of the different size devices were simulated and measured, including temperature distribution, power consumption, thermal expansion and response time. The simulation and electrical-thermal measurement results were reported. For microhotplates with a heat compensation structure, the membrane temperature reached 811.7 °C when the applied voltage was 5.5 V at a heating power of 148.3 mW. A 3.8 V DC voltage was applied to measure the temperature distribution; the maximum temperature was 397.6 °C, and the area where the temperature reached 90% covered about 73.8% when the applied voltage was 3.8 V at a heating power of 70.8 mW. The heating response time was 17 ms while the microhotplate was heated to 400 °C from room temperature, and the cooling response time was 32 ms while the device was recovered to room temperature. This microhotplate has many advantages, such as uniform temperature distribution, low power consumption and fast response, which are suitable for MEMS gas sensors, humidity sensors, gas flow sensors, etc.

Neural stem cell secretome exerts a protective effect on damaged neuron mitochondria in Parkinson's disease model.

Parkinson's disease (PD) is a common neurodegenerative disease. The main pathological changes are the loss of dopaminergic neurons and the formation of Lewy bodies. There is still no effective cure for PD, and cell replacement therapy has entered a bottleneck period due to tumorigenicity and rejection. Therefore, stem cell secretome has received widespread attention. However, the exploration of the secretome components of neural stem cells (NSCs) is still in its infancy. In this study, 6-hydroxydopamine (6-OHDA) was used to establish a PD rat model in vito and the PC12 cell-damaged model in vitro. The results indicated that the injection of neural stem cell-conditioned medium (NSC-CM) into the striatum and substantia nigra could improve the motor and non-motor deficits of PD rats and rescue the loss of dopaminergic neurons. In addition, NSC-CM alleviated 6-OHDA-induced apoptosis of PC12 cells, reduced the level of oxidative stress, and improved mitochondrial dysfunction in vitro. Parkinson disease protein 7 (Park7) was found in NSC-CM by Liquid chromatography-tandem mass spectrometry (LC-MS/MS), and it may be related to the protective effect of NSC-CM on 6-OHDA-injured neurons through Sirt1 pathway. In conclusion, NSC secretome might provide new ideas for the treatment of PD.

Effect of Ultrasound-Assisted Solvent Enzymatic Extraction on Fatty Acid Profiles, Physicochemical Properties, Bioactive Compounds, and Antioxidant Activity of Elaeagnus mollis Oil.

Elaeagnus mollis oil extracted from the nuts of Elaeagnus mollis Diels can be used in food and pharmaceutical applications due to its excellent nutritional value. An ultrasound-assisted solvent enzymatic extraction (UASEE) method was used to extract oil from Elaeagnus mollis Diels with n-hexane solvent (1:11.6 g/mL) and 1.1% (w/w) mixed enzymes (neutral protease:hemicellulase:pectinase = 1:1:1, w/w/w). The physicochemical properties, fatty acid profile, bioactive compounds, antioxidant activity, morphology, and thermal stability of UASEE oil were investigated and compared with soxhlet extraction (SE) oil and cold pressing (CP) oil. The UASEE oil exhibited a higher content of unsaturated fatty acids (93.96 ± 0.28%), total tocopherols and tocotrienols (147.32 ± 2.19 mg/100 g), total phytosterols (261.78 ± 5.74 mg/100 g), squalene (96.75 ± 0.31 mg/100 g), total phenolic content (84.76 ± 2.37 mg GAE/kg), and antioxidant activity (12.52 ± 0.28 mg/mL) than SE and CP oil. The lower peroxide value and acid value in UASEE oil indicated its better quality and lower likelihood of rancidity. The oil obtained using UASEE had higher thermal stability as well, as indicated by thermogravimetric analysis. Scanning electron microscopy (SEM) showed that the UASEE process causes damage to cell walls, and the leakage of substances in the cells facilitates extraction in the following step. Thus, UASEE is a promising processing method for the extraction of Elaeagnus mollis oil.

Redox-sensitive transcriptional regulator SoxR directly controls antibiotic production, development and thiol-oxidative stress response in Streptomyces avermitilis.

The redox-sensitive transcriptional regulator SoxR is conserved in bacteria. Its role in mediating protective response to various oxidative stresses in Escherichia coli and related enteric bacteria has been well established. However, functions and regulatory mechanisms of SoxR in filamentous Streptomyces, which produce half of known antibiotics, are unclear. We report here that SoxR pleiotropically regulates antibiotic production, morphological development, primary metabolism and thiol-oxidative stress response in industrially important species Streptomyces avermitilis. SoxR stimulated avermectin production by directly activating ave structural genes. Four genes (sav_3956, sav_4018, sav_5665 and sav_7218) that are homologous to targets of S. coelicolor SoxR are targeted by S. avermitilis SoxR. A consensus 18-nt SoxR-binding site, 5'-VSYCNVVMHNKVKDGMGB-3', was identified in promoter regions of sav_3956, sav_4018, sav_5665, sav_7218 and target ave genes, leading to prediction of the SoxR regulon and confirmation of 11 new targets involved in development (ftsH), oligomycin A biosynthesis (olmRI), primary metabolism (metB, sav_1623, plcA, nirB, thiG, ndh2), transport (smoE) and regulatory function (sig57, sav_7278). SoxR also directly activated three key developmental genes (amfC, whiB and ftsZ) and promoted resistance of S. avermitilis to thiol-oxidative stress through activation of target trx and msh genes. Overexpression of soxR notably enhanced antibiotic production in S. avermitilis and S. coelicolor. Our findings expand our limited knowledge of SoxR and will facilitate improvement of methods for antibiotic overproduction in Streptomyces species.

Peroxiredoxin 6 secreted by Schwann-like cells protects neuron against ischemic stroke in rats via PTEN/PI3K/AKT pathway.

Schwann cells can promote the survival of damaged neurons and axon regeneration by secreting or releasing some proteins and factors which may provide effective strategies to the remedy for ischemic stroke. The models of middle cerebral artery occlusion and oxygen-glucose deprivation (OGD) were established. Peroxiredoxin 6 (PRDX6) was found in Schwann-like cell conditioned medium (SCLC-CM) by mass spectrometry. The rehabilitative performance of SCLC-CM on focal cerebral ischemia of rats and on OGD-induced PC12 cells were assessed. SCLC-CM significantly improved neurological recovery, reducing the infarct volume of rats after stroke. PRDX6 could significantly inhibit neuron apoptosis in the OGD injury by mediating oxidative stress and activating the PTEN/PI3K/AKT pathway. In conclusion, PRDX6 secreted by Schwann-like cell protects neuron against focal cerebral ischemia, SCLC-CM might be a new effective early intervention for ischemic stroke.

Heat Shock Repressor HspR Directly Controls Avermectin Production, Morphological Development, and H2O2 Stress Response in Streptomyces avermitilis.

The heat shock response (HSR) is a universal cellular response that promotes survival following temperature increase. In filamentous Streptomyces, which accounts for ∼70% of commercial antibiotic production, HSR is regulated by transcriptional repressors; in particular, the widespread MerR-family regulator HspR has been identified as a key repressor. However, functions of HspR in other biological processes are unknown. The present study demonstrates that HspR pleiotropically controls avermectin production, morphological development, and heat shock and H2O2 stress responses in the industrially important species Streptomyces avermitilis. HspR directly activated ave structural genes (aveA1 and aveA2) and H2O2 stress-related genes (katA1, catR, katA3, oxyR, ahpC, and ahpD), whereas it directly repressed heat shock genes (HSGs) (the dnaK1-grpE1-dnaJ1-hspR operon, clpB1p, clpB2p, and lonAp) and developmental genes (wblB, ssgY, and ftsH). HspR interacted with PhoP (response regulator of the widespread PhoPR two-component system) at dnaK1p to corepress the important dnaK1-grpE1-dnaJ1-hspR operon. PhoP exclusively repressed target HSGs (htpG, hsp18_1, and hsp18_2) different from those of HspR (clpB1p, clpB2p, and lonAp). A consensus HspR-binding site, 5'-TTGANBBNNHNNNDSTSHN-3', was identified within HspR target promoter regions, allowing prediction of the HspR regulon involved in broad cellular functions. Taken together, our findings demonstrate a key role of HspR in the coordination of a variety of important biological processes in Streptomyces species. IMPORTANCE Our findings are significant to clarify the molecular mechanisms underlying HspR function in Streptomyces antibiotic production, development, and H2O2 stress responses through direct control of its target genes associated with these biological processes. HspR homologs described to date function as transcriptional repressors but not as activators. The results of the present study demonstrate that HspR acts as a dual repressor/activator. PhoP cross talks with HspR at dnaK1p to coregulate the heat shock response (HSR), but it also has its own specific target heat shock genes (HSGs). The novel role of PhoP in the HSR further demonstrates the importance of this regulator in Streptomyces. Overexpression of hspR strongly enhanced avermectin production in Streptomyces avermitilis wild-type and industrial strains. These findings provide new insights into the regulatory roles and mechanisms of HspR and PhoP and facilitate methods for antibiotic overproduction in Streptomyces species.

Microvesicles from Schwann-Like Cells as a New Biomaterial Promote Axonal Growth.

Schwann cells promote axonal regeneration following peripheral nerve injury. However, in terms of clinical treatment, the therapeutic effects of Schwann cells are limited by their source. The transmission of microvesicles from neuroglia cells to axons is a novel communication mechanism in axon regeneration.To evaluate the effect of microvesicles released from Schwann-like cells on axonal regeneration, neural stem cells derived from human embryonic stem cells differentiated into Schwann-like cells, which presented a typical morphology and characteristics similar to those of schwann cells. The glial markers like MBP, P0, P75NTR, PMP-22, GFAP, HNK-1 and S100 were upregulated, whereas the neural stem markers like NESTIN, SOX1 and SOX2 were significantly downregulated in schwann-like cells. Microvesicles enhanced axonal growth in dorsal root ganglia neurons and regulated GAP43 expression in neuron-like cells (N2A and PC12) through the PTEN/PI3 K/Akt signaling pathway. A 5 mm section of sciatic nerve was transected in Sprague-Dawley rats. With microvesicles transplantation, regenerative nerves were evaluated after 6 weeks. Microvesicles increased sciatic function index scores, delayed gastrocnemius muscle atrophy and elevated ßIII-tubulin-labeled axons in vivo. Schwann-like cells serve as a convenient source and promote axonal growth by secreting microvesicles, which may potentially be used as bioengineering materials for nerve tissue repair.

The ROK-family regulator Rok7B7 directly controls carbon catabolite repression, antibiotic biosynthesis, and morphological development in Streptomyces avermitilis.

Carbon catabolite repression (CCR) is a common phenomenon in bacteria that modulates expression of genes involved in uptake of alternative carbon sources. In the filamentous streptomycetes, which produce half of all known antibiotics, the precise mechanism of CCR is yet unknown. We report here that the ROK-family regulator Rok7B7 pleiotropically controls xylose and glucose uptake, CCR, development, as well as production of the macrolide antibiotics avermectin and oligomycin A in Streptomyces avermitilis. Rok7B7 directly repressed structural genes for avermectin biosynthesis, whereas it activated olmRI, the cluster-situated activator gene for oligomycin A biosynthesis. Rok7B7 also directly repressed the xylose uptake operon xylFGH, whose expression was induced by xylose and repressed by glucose. Both xylose and glucose served as Rok7B7 ligands. rok7B7 deletion led to enhancement and reduction of avermectin and oligomycin A production, respectively, relieved CCR of xylFGH, and increased co-uptake efficiency of xylose and glucose. A consensus Rok7B7-binding site, 5'-TTKAMKHSTTSAV-3', was identified within aveA1p, olmRIp, and xylFp, which allowed prediction of the Rok7B7 regulon and confirmation of 11 additional targets involved in development, secondary metabolism, glucose uptake, and primary metabolic processes. Our findings will facilitate methods for strain improvement, antibiotic overproduction, and co-uptake of xylose and glucose in Streptomyces species.

BldD, a master developmental repressor, activates antibiotic production in two Streptomyces species.

BldD generally functions as a repressor controlling morphological development of Streptomyces. In this work, evidences that BldD also activates antibiotic production are provided. In Streptomyces roseosporus (which produces daptomycin widely used for treatment of human infections), deletion of bldD notably reduced daptomycin production, but enhanced sporulation. BldD stimulated daptomycin production by directly activating transcription of dpt structural genes and dptR3 (which encodes an indirect activator of daptomycin production), and repressed its own gene. BldD-binding sites on promoter regions of dptE, dptR3, and bldD were all found to contain BldD box-like sequences, facilitating prediction of new BldD targets. Two Streptomyces global regulatory genes, adpA and afsR, were confirmed to be directly activated by BldD. The protein AfsR was shown to act as an activator of daptomycin production, but a repressor of development. BldD directly represses nine key developmental genes. In Streptomyces avermitilis (which produces effective anthelmintic agents avermectins), BldD homolog (BldDsav) directly activates avermectin production through ave structural genes and cluster-situated activator gene aveR. This is the first report that BldD activates antibiotic biosynthesis both directly and via a cascade mechanism. BldD homologs are widely distributed among Streptomyces, our findings suggest that BldD may activate antibiotic production in other Streptomyces species.

SAV4189, a MarR-Family Regulator in Streptomyces avermitilis, Activates Avermectin Biosynthesis.

The bacterial species Streptomyces avermitilis is an important industrial producer of avermectins, which are widely utilized as effective anthelmintic and insecticidal drugs. We used gene deletion, complementation, and overexpression experiments to identify SAV4189, a MarR-family transcriptional regulator (MFR) in this species, as an activator of avermectin biosynthesis. SAV4189 indirectly stimulated avermectin production by altering expression of cluster-situated activator gene aveR, and directly repressed the transcription of its own gene (sav_4189) and adjacent cotranscribed gene sav_4190 (which encodes an unknown transmembrane efflux protein). A consensus 13-bp palindromic sequence, 5'-TTGCCYKHRSCAA-3' (Y = T/C; K = T/G; H = A/C/T; R = A/G; S = C/G), was found within the SAV4189-binding sites of its own promoter region, and shown to be essential for binding. The SAV4189 regulon was thus predicted based on bioinformatic analysis. Night new identified SAV4189 targets are involved in transcriptional regulation, primary metabolism, secondary metabolism, and stress response, reflecting a pleiotropic role of SAV4189. sav_4190, the important target gene of SAV4189, exerted a negative effect on avermectin production. sav_4189 overexpression and sav_4190 deletion in S. avermitilis wild-type and industrial strains significantly increased avermectin production. SAV4189 homologs are widespread in other Streptomyces species. sav_4189 overexpression in the model species S. coelicolor also enhanced antibiotic production. The strategy of increasing yield of important antibiotics by engineering of SAV4189 homologs and target gene may potentially be extended to other industrial Streptomyces species. In addition, SAV4189 bound and responded to exogenous antibiotics hygromycin B and thiostrepton to modulate its DNA-binding activity and transcription of target genes. SAV4189 is the first reported exogenous antibiotic receptor among Streptomyces MFRs.

[Study on esterified modification of anthocyanins by FTIR].

Anthocyanins are relatively abundant in vegetables and fruits, which have potential positive health effects. The role of anthocyanins as food coloring agents becomes very important because they can provide attractive bright color of many food products. Nevertheless, the instability of natural anthocyanins was a big obstacle for its usage in food as colorants. The stability of the red radish anthocyanins is significantly improved by modified esterification of the colorant. Usually, the red radish anthocyanins was composed of several components of similar structures. The major methods for determining the structures of anthocyanin colorants involve chromatographic techniques such as TLC, HPLC and HPLC-MS, which are very useful in separation and identification of the components of anthocyanins However, compared to the spectroscopic method, the chromatographic methods are usually complicated and time-consuming during separation and analysis. In the present paper, the authors seek to establish a new, rapid and economic method for the analysis of structural change before and after esterified modification of anthcyanins in view of unique macro-fingerprint characteristics of infrared spectroscopy, which could reflect the whole change of complicated mixture system. The anthocyanins from red radish was esterification-modified by reacting with succinic anhydride, and the natural and modified anthocyanins were detected by FTIR The results showed that carbonyl of succinic anhydride was connected with the hydroxyl in glucosyl rings of anthocyanins to form new esterified anthocyanins, which are more stable than the natural one and present attractive bright color as usual.

[Talk about nomenclature of twelve meridians from quantitative yin-yang theory].

Based on leads provided by Neijing and other literature, analyze origins of the three-yin and the three-yang and the their respective contents of yin and yang, indicating the principle that the order of yang-qi from more to less is Yang ming, Tai yang, Shao yang, and the order of yin-qi is Tai yin, Shao yin, Jue yin. According to the location of five (six) zang-organs, respective yin-qi content is defined, and according to the principle of more yin-qi matches more, and less yin-qi matches less, five (six) zang-organs match each other. The zang-organs above the diaphragm joints with The Hand-Channels and the zang-organs below the diaphragm with The Foot-Channels, completing the nomenclature of twelve meridians. The names of the six yang-channels correspond to the yin-channels of the exterior-interior relationship, the yin-channels link with hands (feet), and the yang-channels also link with hands (feet), and the amount of yin-qi of the zang-organs corresponding to the yin-channels and the amount of yang-qi of the fu-organs corresponding to yang-channels are in a state of balance. Based on this principle, nomenclature of six channels are completed. Emphasize that the nomenclature of twelve meridians contains profound TCM theories, especially, TCM, by yin-yang, three-yin and three- yang, illustrates living phenomena from the whole to the system and organ level in human body, and the scientific principle "yin-yang can be unlimitedly divided" and its significance, which must guide the studies on living phenomena with modern life sciences from the whole to the molecular level.

[Manipulation methods of slow-rapid reinforcing-reducing method].

After consulting literature, following the original meaning of the paper about slow-rapid reinforcing-reducing method in Huangdi's Internal Classic, in combination with explanation of later ages, and comprehension and clinical experience of the authors, it is put forward that the slow-rapid reinforcing-reducing method in Huangdi's Internal Classic is not single manipulation method, but it is a guiding principle for reinforcing-reducing manipulation, it includes many manipulation methods and they were listed, and all of the reinforcing-reducing methods of later ages are developed from these. In the teaching material Acupuncture and Moxibustion Sciences they are included in single reinforcing-reducing method, reducing extension and intension of this definition. The relative description in the teaching material only is slow-rapid reinforcing-reducing method of narrow sense, but the manipulations can be divided into qi-carrying manipulating needle type and three-one pushing-pulling type.

[Multi-central clinical evaluation of ginger-partitioned moxibustion for treatment of leukopenia induced by chemotherapy].

OBJECTIVE: To prove the therapeutic effect of ginger-partitioned moxibustion on leukopenia induced by chemotherapy and effect on life quality of the patient with tumor after chemotherapy. METHODS: Randomized, controlled, multi-central cooperative method was used and the patients confirmed to the enrolled criteria were divided in-to two groups. The test group were treated with ginger-partitioned moxibustion at Dazhui (GV 14), Geshu (BL 17), Pishu (BL 20), etc.; and the control group with oral administration of Chinese patent medicine. RESULTS: Out of the 221 cases confirmed to program analysis, 113 cases were in the test group and 108 cases in the control group. After 10 days, the cured rate and the effective rate were 84.1% and 66.4% in the test group and 35.2% and 33.3% in the control group, respectively, with very significant differences between the two groups (both P < 0.01); fifteen days later, the therapeutic effects in the two groups were maintained. The two methods could improve clinical symptoms, with the test group being better than the control group. Any adverse response was not found in the two groups, and the injuries of functions of the heart, lung and kidney induced by chemotherapy had some improvement. CONCLUSION: The therapeutic effect of ginger-partitioned moxibustion on luekopenia induced by chemotherapy is reliable and is better than oral administration of Chinese patent medicine, with a better duplication.