In this paper, a 16-channel analog front-end (AFE) electrocorticography signal acquisition circuit for a closed-loop seizure control system is presented. It is composed of 16 input protection ...circuits, 16 auto-reset chopper-stabilized capacitive-coupled instrumentation amplifiers (AR-CSCCIA) with bandpass filters, 16 programmable transconductance gain amplifiers, a multiplexer, a transimpedance amplifier, and a 128-kS/s 10-bit delta-modulated successive-approximation-register analog-to-digital converter (SAR ADC). In closed-loop seizure control system applications, the stimulator shares the same electrode with the AFE amplifier for effective suppression of epileptic seizures. To prevent from overstress in MOS devices caused by high stimulation voltage, an input protection circuit with a high-voltage-tolerant switch is proposed for the AFE amplifier. Moreover, low input-referred noise is achieved by using the chopper modulation technique in the AR-CSCCIA. To reduce the undesired effects of chopper modulation, an improved offset reduction loop is proposed to reduce the output offset generated by input chopper mismatches. The digital ripple reduction loop is also used to reduce the chopper ripple. The fabricated AFE amplifier has 49.1-/59.4-/67.9-dB programmable gain and 2.02-μVrms input referred noise in a bandwidth of 0.59-117 Hz. The measured power consumption of the AFE amplifier is 3.26 μW per channel, and the noise efficiency factor is 3.36. The in vivo animal test has been successfully performed to verify the functions. It is shown that the proposed AFE acquisition circuit is suitable for implantable closed-loop seizure control systems.
The intestinal mucosal barrier (IMB) enables the intestine to provide adequate containment of luminal microorganisms and molecules while preserving the ability to absorb nutrients. In this study, we ...explored the effect of brain-derived neurotrophic factor (BDNF) on IMB function and gut microbiota in mice. BDNF gene knock-out mice (the BDNF+/− group) and wild-type mice (the BDNF+/+ group) were selected. The gut microbiota of these mice was analyzed by denaturing gradient gel electrophoresis (DGGE) assay. The ultrastructure of the ileum and the colonic epithelium obtained from decapitated mice were observed by transmission electron microscopy. The protein expression of epithelial tight junction proteins, zonula occludens-1 (ZO-1) and occludin was detected by immunohistochemistry staining. The protein expression of claudin-1 and claudin-2 was determined by Western blotting. The DGGE band patterns of gut microbiota in the BDNF+/− group were significantly different from that in the BDNF+/+ group, which indicated that the BDNF expression alters the gut microbiota in mice. Compared with the BDNF+/+ group, the BDNF+/− group presented no significant difference in the ultrastructure of ileal epithelium; however, a significant difference was observed in the colonic epithelial barrier, manifested by decreased microvilli, widening intercellular space and bacterial invasion. Compared with the BDNF+/+ group, the expression of ZO-1 and occludin in the BDNF+/− group was significantly decreased. The expression of claudin-1 in the BDNF+/− group was significantly reduced, while the expression of claudin-2 was elevated. These findings indicate that BDNF preserves IMB function and modulates gut microbiota in mice.
Optically transparent polymer films with excellent thermal and ultraviolet (UV) resistance have been highly desired in advanced optoelectronic fields, such as flexible substrates for photovoltaic ...devices. Colorless and transparent polyimide (CPI) films simultaneously possess the good thermal stability and optical transparency. However, conventional CPI films usually suffered from the UV exposure and have to face the deterioration of optical properties during the long-term service in UV environments. In the current work, the commercially available hindered amine light stabilizers (HALS) were tried to be incorporated into the semi-alicyclic CPI matrix with the aim of enhancing the UV exposure stability. For this target, a CPI-0 film was first prepared from hydrogenated pyromellitic dianhydride (HPMDA) and 2,2'-dimethylbenzidine (DMBZ) via a one-step polycondensation procedure. Then, the commercially available HALS were incorporated into the CPI-0 (HPMDA-DMBZ) film matrix to afford four series of CPI/HALS composite films. Experimental results indicated that the Tinuvin
791 HALS showed the best miscibility with the CPI-0 film matrix and the derived CPI-D series of composite films exhibited the best optical transmittances. The CPI-D nanocomposite films showed apparently enhanced UV exposure stability via incorporation of the 791 additives. For the pristine CPI-0 film, after the UV exposure for 6 h, the optical properties, including the transmittance at the wavelength of 350 nm (
), lightness (
*), yellow indices (
*), and haze obviously deteriorated with the
values from 55.7% to 17.5%, the
* values from 95.12 to 91.38, the
* values from 3.38 to 21.95, and the haze values from 1.46% to 9.33%. However, for the CPI-D-10 film (791: CPI-0 = 1.0 wt%, weight percent), the optical parameters were highly maintained with the
values from 61.4% to 53.8%, the
* values from 95.46 to 95.36, the
* values from 1.84 to 1.51, and the haze values from 0.69% to 3.34% under the same UV aging conditions.
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•The senescence of activated HSCs restricts the liver fibrosis.•IL-10 induces directly the senescence of activated HSCs to attenuate liver fibrosis.•IL-10 induced senescence of ...activated HSCs via STAT3-p53 pathway in vitro.
Hepatic fibrosis is a wound healing process which results in deposition of excessive abnormal extracellular matrix (ECM) in response to various liver injuries. Activated hepatic stellate cells (HSCs) are the major sources of ECM and induction of senescence of activated HSCs is an attractive therapeutic strategy for liver fibrosis. Our previous studies have shown that interleukin-10 (IL-10) attenuates the carbon tetrachloride (CCL4) - and porcine serum-induced liver fibrosis in rats. However, little is known about the mechanisms of IL-10 regulating the senescence of activated HSCs. The aim of this study is to uncover the underlying pathway by which IL-10 mediates activated HSCs senescence to attenuate liver fibrosis. In vivo, we found that IL-10 gene by hydrodynamics-based transfection attenuated CCL4-induced liver fibrosis associated with senescence of activated HSCs in rats. In vitro experiment confirmed that IL-10 could induce senescence of activated HSCs via inhibiting cell proliferation, inducing cell cycle arrest, increasing the SA-β-Gal activity and enhancing expression of senescence marker protein p53 and p21. Treatment with Pifithrin-α, a specific inhibitor of p53, could abrogate IL-10-increased SA-β-Gal activity and expression of P53 and P21in activated HSCs. Lastly, IL-10 also increased the expression of total and phosphorylated signal transducers and activators of transcription 3(STAT3) and promoted phosphorylated STAT3 translocation from cytoplasm to nucleus. Treatment with cryptotanshinone, a specific inhibitor of STAT3, could inhibit the phosphorylation of STAT3 and its downstream proteins p53 and p21 expression and decrease the activity of SA-β-Gal in activated HSCs induced by IL-10. Taken together, IL-10 induced senescence of activated HSCs via STAT3-p53 pathway to attenuate liver fibrosis in rats and present study will provide a new mechanism of antifibrotic effects of IL-10.
Semi-supervised video object segmentation is the process of tracking and segmenting objects in a video sequence based on annotated masks for one or more frames. Recently, memory-based methods have ...attracted a significant amount of attention due to their strong performance. Having too much redundant information stored in memory, however, makes such methods inefficient and inaccurate. Moreover, a global matching strategy is usually used for memory reading, so these methods are susceptible to interference from semantically similar objects and are prone to incorrect segmentation. We propose a spatial constraint network to overcome these problems. In particular, we introduce a time-varying sensor and a dynamic feature memory to adaptively store pixel information to facilitate the modeling of the target object, which greatly reduces information redundancy in the memory without missing critical information. Furthermore, we propose an efficient memory reader that is less computationally intensive and has a smaller footprint. More importantly, we introduce a spatial constraint module to learn spatial consistency to obtain more precise segmentation; the target and distractors can be identified by the learned spatial response. The experimental results indicate that our method is competitive with state-of-the-art methods on several benchmark datasets. Our method also achieves an approximately 30 FPS inference speed, which is close to the requirement for real-time systems.
•Time-varying sensor and dynamic feature memory reduce redundancy but retain key data.•Efficient memory reader has smaller footprint and reduces computational overhead.•Spatial constraint module maintains response map to filter visually similar objects.
Cleavage of transfer (t)RNA and ribosomal (r)RNA are critical and conserved steps of translational control for cells to overcome varied environmental stresses. However, enzymes that are responsible ...for this event have not been fully identified in high eukaryotes. Here, we report a mammalian tRNA/rRNA-targeting endoribonuclease: SLFN13, a member of the Schlafen family. Structural study reveals a unique pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N'-domain that may clamp base-paired RNAs. SLFN13 is able to digest tRNAs and rRNAs in vitro, and the endonucleolytic cleavage dissevers 11 nucleotides from the 3'-terminus of tRNA at the acceptor stem. The cytoplasmically localised SLFN13 inhibits protein synthesis in 293T cells. Moreover, SLFN13 restricts HIV replication in a nucleolytic activity-dependent manner. According to these observations, we term SLFN13 RNase S13. Our study provides insights into the modulation of translational machinery in high eukaryotes, and sheds light on the functional mechanisms of the Schlafen family.
Flavonoids are one of the key secondary metabolites determining the quality of tea. Although exogenous brassinosteroid (BR), a steroidal plant hormone, can stimulate polyphenol biosynthesis in tea ...plants (Camellia sinensis L.), the relevance of endogenous BR in flavonoid accumulation and the underlying mechanisms remain largely unknown. Here we show that BR enhances flavonoid concentration in tea leaves by inducing an increase in the endogenous concentration of nitric oxide (NO). Notably, exogenous BR increased levels of flavonoids as well as NO in a concentration dependent manner, while suppression of BR levels by an inhibitor of BR biosynthesis, brassinazole (BRz), decreased the concentrations of both flavonoids and NO in tea leaves. Interestingly, combined treatment of BR and BRz reversed the inhibitory effect of BRz alone on the concentrations of flavonoids and NO. Likewise, exogenous NO also increased flavonoids and NO levels dose-dependently. When the NO level in tea leaves was suppressed by using a NO scavenger, 2,4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), flavonoid concentration dramatically decreased. Although individual application of 0.1μM BR increased the concentrations of flavonoids and NO, combined treatment with exogenous NO scavenger, cPTIO, reversed the effect of BR on flavonoid concentration. Furthermore, BR or sodium nitroprusside (SNP) promoted but cPTIO inhibited the transcription and activity of phenylalanine ammonia-lyase (PAL) in leaves, while combined treatment of BR with SNP or cPTIO had no additive effect. The results of this study suggest that an optimal level of endogenous NO is essential for BR-induced promotion of flavonoid biosynthesis in tea leaves. In conclusion, this study unveiled a crucial mechanism of BR-induced flavonoid biosynthesis, which might have potential implication in improving the quality of tea.
Recharge mileage is of great importance for a hydrogen fuel cell electric vehicle. High pressure hydrogen storage can increase the recharge mileage significantly. Before hydrogen flows into the fuel ...cell, a decompression process is necessary. To overcome the seal of the piping system and realize the decompression, Tesla valve can be well used, since it is a type of check valve without moving parts, and when there is a reverse flow, large pressure drop appears between the inlet and outlet. In order to obtain a better pressure drop performance for a Tesla valve, in this paper, the structural parameters including the hydraulic diameter, the valve angle, and the inner curve radius are investigated for a large range of inlet velocities. The results indicate that a small hydraulic diameter and small inner curve radius but large valve angle can provide a higher pressure drop under a large inlet velocity, while the pressure drop under different structural parameters barely changes under a small inlet velocity (less than 100 m/s). Besides, there is a low-pressure zone behind the outlet of the bend channel, which should be paid attention. This work can be referred by the further applications of Tesla valves in hydrogen fuel cell electric vehicles for hydrogen decompression.
•Tesla valves can be well used for hydrogen decompression.•Structural parameters of Tesla valves for hydrogen decompression are investigated.•Pressure distribution in Tesla valves is analyzed under different inlet velocities.•High pressure drop can be achieved with small hydraulic diameter and inner curve radius but large valve angle.•A low-pressure region behind the bend channel and should be considered.
This study aimed to investigate the impact of body mass index (BMI) on the short-term and long-term results of a large cohort of gastric cancer (GC) patients undergoing gastrectomy.Recently, the ..."obesity paradox" has been proposed, referring to the paradoxically "better" outcomes of overweight and obese patients compared with nonoverweight patients. The associations between BMI and surgical outcomes among patients with GC remain controversial.A single-institution cohort of 1249 GC patients undergoing gastrectomy between 2000 and 2010 were categorized to low-BMI (<18.49 kg/m), normal-BMI (18.50-24.99 kg/m), and high-BMI (≥25.00 kg/m) groups. The postoperative complications were classified according to the Clavien-Dindo system, and their severity was assessed by using the Comprehensive Complication Index (CCI). The impact of BMI on the postoperative complications and overall survival was analyzed.There were 908, 158, and 182 patients in the normal-BMI, low-BMI, and high-BMI groups, respectively. The overall morbidity in the high-BMI group (24.7%) was higher than that in either the low-BMI or the normal-BMI group (20.9% and 15.5%, respectively; P = 0.006), but the mean CCI in the low-BMI group was significantly higher (8.32 ± 19.97) than the mean CCI in the normal-BMI and high-BMI groups (3.76 ± 11.98 and 5.58 ± 13.07, respectively; P < 0.001). The Kaplan-Meier curve and the log-rank test demonstrated that the low-BMI group exhibited the worst survival outcomes compared with the normal-BMI group, whereas the high-BMI group exhibited the best survival outcomes (P < 0.001). In multivariate analysis, BMI was identified as an independent prognostic factor. In the stage-specific subgroup analysis, a low BMI was associated with poorer survival in the cases of stage III-IV diseases.Low BMI was associated with more severe postoperative complications and poorer prognosis. Despite a higher risk of mild postoperative complications, the high-BMI patients exhibited paradoxically "superior" survival outcomes compared with the normal-BMI patients. These findings confirm the "obesity paradox" in GC patients undergoing gastrectomy.
Receptor activator of NF‐κB ligand (RANKL) is essential for osteoclast formation and bone remodeling. Nevertheless, the cellular source of RANKL for osteoclastogenesis has not been fully uncovered. ...Different from peripheral adipose tissue, bone marrow (BM) adipose lineage cells originate from bone marrow mesenchymal stromal cells (BMSCs). Here, we demonstrate that adiponectin promoter‐driven Cre expression (AdipoqCre) can target bone marrow adipose lineage cells. We cross the AdipoqCre mice with ranklfl/fl mice to conditionally delete RANKL from BM adipose lineage cells. Conditional deletion of RANKL increases cancellous bone mass of long bones in mice by reducing the formation of trabecular osteoclasts and inhibiting bone resorption but does not affect cortical bone thickness or resorption of calcified cartilage. AdipoqCre; ranklfl/fl mice exhibit resistance to estrogen deficiency and rosiglitazone (ROS)‐induced trabecular bone loss but show bone loss induced by unloading. BM adipose lineage cells therefore represent an essential source of RANKL for the formation of trabecula osteoclasts and resorption of cancellous bone during remodeling under physiological and pathological conditions. Targeting bone marrow adiposity is a promising way of preventing pathological bone loss.
Synopsis
RANKL is essential for osteoclast formation and bone remodeling, but the cellular source for osteoclastogenesis has not been fully uncovered. Bone marrow adipose lineage cells are essential RANKL sources for trabecular osteoclast formation and bone resorption in the context of pathological bone loss.
The AdipoqCre line targets bone marrow adipose lineage cells.
Conditional knockout of RANKL in bone marrow adipose lineage cells increases cancellous bone mass by reducing formation of trabecular osteoclasts and inhibiting bone resorption.
AdipoqCre; ranklfl/fl mice exhibit resistance to estrogen deficiency and rosiglitazone induced trabecular bone loss but show bone loss induced by unloading.
Bone marrow adipose lineage cells are an essential source of RANKL for trabecular osteoclast formation and bone resorption in the context of pathological bone loss.
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