Vitamin D inhibits ferroptosis and mitigates the kidney injury of prediabetic mice by activating the Klotho/p53 signaling pathway.

Diabetic nephropathy (DN) is a serious public health problem worldwide, and ferroptosis is deeply involved in the pathogenesis of DN. Prediabetes is a critical period in the prevention and control of diabetes and its complications, in which kidney injury occurs. This study aimed to explore whether ferroptosis would induce kidney injury in prediabetic mice, and whether vitamin D (VD) supplementation is capable of preventing kidney injury by inhibiting ferroptosis, while discussing the potential mechanisms. High-fat diet (HFD) fed KKAy mice and high glucose (HG) treated HK-2 cells were used as experimental subjects in the current study. Our results revealed that serious injury and ferroptosis take place in the kidney tissue of prediabetic mice; furthermore, VD intervention significantly improved the kidney structure and function in prediabetic mice and inhibited ferroptosis, showing ameliorated iron deposition, enhanced antioxidant capability, reduced reactive oxygen species (ROS) and lipid peroxidation accumulation. Meanwhile, VD up-regulated Klotho, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, and down-regulated p53, transferrin receptor 1 (TFR1) and Acyl-Coenzyme A synthetase long-chain family member 4 (ACSL4) expression. Moreover, we demonstrated that HG-induced ferroptosis is antagonized by treatment of VD and knockdown of Klotho attenuates the protective effect of VD on ferroptosis in vitro. In conclusion, ferroptosis occurs in the kidney of prediabetic mice and VD owns a protective effect on prediabetic kidney injury, possibly by via the Klotho/p53 pathway, thus inhibiting hyperglycemia-induced ferroptosis.

Type 2 diabetes associated with areca nut usage: A systematic review and meta-analysis.

AIMS/HYPOTHESIS: This study aimed to evaluate the potential association between chewing areca nuts and the occurrence of type 2 diabetes and to investigate whether chewing status (current chewers or ex-chewers) affects this association. METHODS: We searched The Cochrane Library, PubMed, and EMBASE databases for relevant studies up to May 21, 2023, using predefined inclusion and exclusion criteria. Three population-based studies conducted in Taiwan were included in the systematic review and meta-analysis. RESULTS: When combined current or ex-chewers were more likely to develop diabetes (Odds Ratio [OR] = 1.45; 95% confidence interval [CI]: 1.30-1.62) compared to the never chewers. Ex-chewers had a higher risk of diabetes (OR: 1.53, 95% CI: 1.45-1.62) compared to never chewers. However, there was no evidence that current chewers were associated with a higher risk of diabetes compared to never chewers. Male current and ex-chewers were associated with higher risk of diabetes compared with never chewers (OR: 1.55, 95% CI: 1.49-1.61). For females there was insufficient evidence. CONCLUSIONS/INTERPRETATION: Existing evidence suggests a link between chewing areca nuts and the development of type 2 diabetes. Therefore, areca chewers should monitor diabetes-related biomarkers.

DMAF-NET: Deep Multi-Scale Attention Fusion Network for Hyperspectral Image Classification with Limited Samples.

In recent years, deep learning methods have achieved remarkable success in hyperspectral image classification (HSIC), and the utilization of convolutional neural networks (CNNs) has proven to be highly effective. However, there are still several critical issues that need to be addressed in the HSIC task, such as the lack of labeled training samples, which constrains the classification accuracy and generalization ability of CNNs. To address this problem, a deep multi-scale attention fusion network (DMAF-NET) is proposed in this paper. This network is based on multi-scale features and fully exploits the deep features of samples from multiple levels and different perspectives with an aim to enhance HSIC results using limited samples. The innovation of this article is mainly reflected in three aspects: Firstly, a novel baseline network for multi-scale feature extraction is designed with a pyramid structure and densely connected 3D octave convolutional network enabling the extraction of deep-level information from features at different granularities. Secondly, a multi-scale spatial-spectral attention module and a pyramidal multi-scale channel attention module are designed, respectively. This allows modeling of the comprehensive dependencies of coordinates and directions, local and global, in four dimensions. Finally, a multi-attention fusion module is designed to effectively combine feature mappings extracted from multiple branches. Extensive experiments on four popular datasets demonstrate that the proposed method can achieve high classification accuracy even with fewer labeled samples.

Maresin1 alleviates neuroinflammation by inhibiting caspase-3/ GSDME-mediated pyroptosis in mice cerebral ischemia-reperfusion model.

OBJECTIVE: To explore the mechanism of Maresin1 in reducing cerebral ischemia-reperfusion injury. MATERIALS AND METHODS: Male C57BL/6 mice were randomly divided (n = 5 in each group), and focal middle cerebral artery occlusion (MCAO) model was used to simulate cerebral ischemia/reperfusion injury. TTC and the Longa score were used to detect the degree of neurological deficits. Western blot was used to detect the expression levels of GSDME, GSDME-N, caspase-3 and cleaved caspase-3 in cerebral ischemic penumbra tissue, and immunofluorescence was used to detect the expression levels of GSDME-N. The mRNA expression levels of GSDME and pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) were detected by RT-PCR. RESULTS: Compared with sham group, GSDME mRNA levels in MCAO group were significantly increased at 12 h and 24 h after reperfusion, and GSDME and GSDME-N significantly increased at 6-48 h after reperfusion. Compared with sham group, the percentage of infarct size, the Longa score, the mRNA expression levels of IL-1ß, IL-6 and TNF-α, and GSDME, GSDME-N, caspase-3 and cleaved caspase-3 in MCAO group was significantly increased. Then, the percentage of infarct size and the Longa score significantly decreased after MaR1 administration, the mRNA expression levels of IL-1ß and IL-6 downregulated, and GSDME, GSDME-N, caspase-3 and cleaved caspase-3 were also reduced. After administration of Z-DEVD-FMK(ZDF), the expression of caspase-3, cleaved caspase-3 and GSDME-N was decreased, which in MCAO+MaR1+ZDF group was not statistically significant compared with MCAO+ ZDF group. CONCLUSION: Maresin1 alleviates cerebral ischemia/reperfusion injury by inhibiting pyroptosis mediated by caspase-3/GSDME pathway and alleviating neuroinflammation.

CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of subpopulation of AEC2s.

BACKGROUND: Functional alveolar regeneration is essential for the restoration of normal lung homeostasis after acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Lung is a relatively quiescent organ and a variety of stem cells are recruited to participate in lung repair and regeneration after lung tissue injury. However, there is still no effective method for promoting the proliferation of endogenous lung stem cells to promote repair and regeneration. METHODS: Using protein mass spectrometry analysis, we analyzed the microenvironment after acute lung injury. RNA sequencing and image cytometry were used in the alveolar epithelial type 2 cells (AEC2s) subgroup identification. Then we used Sftpc+AEC2 lineage tracking mice and purified AEC2s to further elucidate the molecular mechanism by which CTGF regulates AEC2s proliferation both in vitro and in vivo. Bronchoalveolar lavage fluid (BALF) from thirty ARDS patients who underwent bronchoalveolar lavage was collected for the analysis of the correlation between the expressing of Krt5 in BALF and patients' prognosis. RESULTS: Here, we elucidate that AEC2s are the main facultative stem cells of the distal lung after ALI and ARDS. The increase of connective tissue growth factor (CTGF) in the microenvironment after ALI promoted the proliferation of AEC2s subpopulations. Proliferated AEC2s rapidly expanded and differentiated into alveolar epithelial type 1 cells (AEC1s) in the regeneration after ALI. CTGF initiates the phosphorylation of LRP6 by promoting the interaction between Krt5 and LRP6 of AEC2s, thus activating the Wnt signaling pathway, which is the molecular mechanism of CTGF promoting the proliferation of AEC2s subpopulation. CONCLUSIONS: Our study verifies that CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of AEC2s subpopulation.

A New Method for Programmable RNA Editing Using CRISPR Effector Cas13X.1.

Type VI CRISPR-Cas13 is the only CRISPR system that can bind and cleave RNA without DNase activity. We used the newly discovered, smaller Cas13X.1 protein to construct an editing system in mammalian cells, aiming to break the delivery restrictions of CRISPR-Cas13 system in vivo and promote the application of Cas13X system in clinical therapy. We employed exogenous fluorescence reporter gene mCherry and endogenous gene transketolase (TKT) closely related to cancer cell metabolism as target genes to evaluate the Cas13X.1 system. The recombinant plasmids targeting exogenous gene mCherry and endogenous gene TKT were constructed based on Cas13X.1 backbone plasmid. The editing efficiency, protein expression level, downstream gene transcript level and safety of Cas13X.1 system were evaluated. Both TKT transcripts of endogenous genes and mCherry transcripts of exogenous genes were significantly degraded by Cas13X.1 system with a knockdown efficiency up to 50%. At the same time, Cas13X.1 down-regulated the expression of the corresponding protein level in the editing of transcripts. In addition, the transcripts of key metabolic enzymes related to TKT were also down-regulated synchronously, suggesting that the degradation of TKT transcripts by Cas13X.1 system affected the main metabolic pathways related to TKT. The morphology, RNA integrity and apoptosis of cells loaded with Cas13X.1 system were not affected. The Cas13X.1 system we constructed had strong RNA knockdown ability in mammalian cells with low cellular toxicity. Compared with other CRISPR-Cas13 systems, Cas13X.1 system with smaller molecular weight has more advantages in vivo delivery. The Cas13X.1 system targeting TKT transcripts also provides an alternative method for the study of anti-cancer therapy.

A nomogram for predicting overall survival of patients with squamous cell carcinoma of the floor of the mouth: a population-based study.

BACKGROUND: Floor of mouth squamous cell carcinoma (SCCFOM) is a rare but aggressive malignancy with 5-year overall survival (OS) rates below 40% in published studies. However, the clinicopathological predictors of the prognosis of SCCFOM remain undefined. We aimed to establish a model to predict the survival outcomes of SCCFOM. METHODS: We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with SCCFOM between 2000 and 2017. Data on patient demographics, treatment modalities, and survival outcomes were retrieved. Risk factors for OS were evaluated by survival and Cox regression analyses. A nomogram for OS was developed based on the multivariate model and split the patients into high- and low-risk cohorts based on cutoff values. RESULTS: Overall, 2014 SCCFOM patients were included in this population-based study. Multivariate Cox regression showed that age, married status, grade, American Joint Committee on Cancer stage, radiotherapy, chemotherapy, and surgery were significant risk factors for survival. A nomogram was established using the regression model. The C-indices, areas under the receiver operating characteristic curves, and calibration plots demonstrated the reliable performance of the nomogram. Patients assigned to the high-risk group had a significantly lower survival rate. CONCLUSIONS: The nomogram predicting survival outcomes of SCCFOM patients based on clinical information showed good discriminative ability and prognostic accuracy. Our nomogram could be used to predict the survival probabilities for SCCFOM patients at different timepoints.

Electrotaxis of alveolar epithelial cells in direct-current electric fields.

PURPOSE: This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury. METHODS: AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis. RESULTS: The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11. CONCLUSION: EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.

Aumolertinib-based comprehensive treatment for an uncommon site of EGFR exon 20 insertion mutations with multiple metastases non-small cell lung cancer: a case report.

EGFR exon 20 insertion mutation is a rare mutation subtype of EGFR mutations, with no approved treatment in China so far. The clinical treatments of advanced EGFR exon 20 insertion mutations in non-small cell lung cancer (NSCLC) are mainly based on EGFR-TKI, chemotherapy, ICI, and other therapies. However, the efficacy is not satisfactory. Aumolertinib is the third-generation EGFR-TKI independently developed in China, which has shown excellent efficacy and safety in phase 2 and 3 clinical trials. This study aimed to share a case of applying aumolertinib as the core combined with other treatments for a patient with multiple metastases in NSCLC with an uncommon site of EGFR exon 20 insertion mutations. The comprehensive treatment benefited the patient in terms of 10 months of progression-free survival and a significant improvement in quality of life. We discussed whether we could further explore the potential of aumolertinib in treating EGFR exon 20 insertion mutations through this case report.

NLRC5 modulates bone metabolism and plays a role in periodontitis.

INTRODUCTION: NOD-like receptor C5 (NLRC5) plays a significant role in the immune system, and is one of the largest members of the pattern recognition receptor family. Previous studies have found that NLRC5 might be involved in the regulation of various diseases, such as fibrotic diseases and cancers; however, its effect on bone metabolism-related diseases has not been reported. METHODS: Skeletons of Nlrc5-/- mice generated by CRISPR/Cas9 and wild-type (WT) mice were compared using X-ray, micro-computed tomography, double labeling, and histological examination. Tartrate-resistant acid phosphatase and pit-absorption assays were performed to evaluate the effect of NLRC5 on osteoclasts differentiation and osteoclastic capacity. The influence of NLRC5 on osteoblasts differentiation and bone formation were studied using alkaline phosphatase and alizarin red staining, respectively. Experimental periodontitis was induced by Porphyromonas gingivalis infection and ligature to investigate the role of NLRC5 in inflammatory periodontal bone loss. RESULTS: Adenovirus-mediated NLRC5 overexpression in human bone marrow mesenchymal stem cells regulated osteogenesis positively. The femoral osteogenesis ability was significantly weakened in Nlrc5-/- mice. Histology showed that the area of the femoral trabeculae in the Nlrc5-/- mice was less than that in the WT mice, and radiology suggested that the Nlrc5-/- mice had fewer trabeculae and a thinner bone cortex than those of the WT mice. Nlrc5 knockout decreased osteoblast mineralization and increased osteoclastogenesis in vitro. NLRC5 was downregulated in periodontitis and P. gingivalis infection. In the experimental periodontitis model, the alveolar bone loss, inflammatory cell infiltration, and inflammatory cytokines secretion (interleukin [IL]-1ß, IL-6, and tumor necrosis factor alpha [TNF-α]) in the Nlrc5-/- mice were significantly enhanced compared to WT mice. CONCLUSION: We verified a novel role of NLRC5 in bone metabolism by regulating both osteoclasts activity and osteoblasts activity. Our results revealed a protective effect of NLRC5 against periodontal inflammation and alveolar bone destruction. NLRC5 could be a novel treatment target to prevent periodontal bone destruction.

Efficacy of periodontal minimally invasive surgery with and without regenerative materials for treatment of intrabony defect: a randomized clinical trial.

OBJECTIVES: The minimally invasive surgical technique was modified in suture (MISTms) in this study. The trial was to determine the efficacy of MISTms with and without regenerative materials for the treatment of intrabony defect and to identify factors influencing 1-year clinical attachment level (CAL) gain. METHODS: Thirty-six patients with interdental intrabony defects were randomly assigned to MISTms (MISTms alone, 18) or MISTms plus deproteinized bovine bone mineral and collagen membrane (MISTms combined, 18). Wound healing was evaluated by early healing index (EHI) at 1, 2, 3, and 6 weeks. Probing depth (PD), CAL, gingival recession, radiographic defect depth, and distance from the base of defect to the cementoenamel junction were recorded at baseline and 1 year postoperatively. A one-year composite outcome measure based on the combination of CAL gain and post-surgery PD was evaluated. Factors influencing 1-year CAL gain were analyzed. RESULTS: Fifteen patients in MISTms-alone and 16 in the MISTms-combined group finished the study. The MISTms-alone group showed significantly better wound healing at 1 week. CAL significantly gained in the MISTms-alone and MISTms-combined group, with 2.53 ± 1.80 mm and 2.00 ± 1.38 mm respectively. The radiographic bone gain was 3.00 ± 1.56 mm and 3.85 ± 1.69 mm respectively. However, there were no significant differences between the two groups about 1-year outcomes. Lower EHI (optimal wound healing) and more baseline CAL positively influenced 1-year CAL gain. CONCLUSIONS: MISTms is an effective treatment for intrabony defects. The regenerative materials do not show an additional effect on 1-year outcomes. Early wound healing and baseline CAL are factors influencing 1-year CAL gain. CLINICAL RELEVANCE: MISTms with and without regenerative materials are both effective treatments for intrabony defect. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR2100043272.

Impact of Wedge Parameters on Ultrasonic Lamb Wave Liquid-Level Sensor.

The ultrasonic Lamb wave detection principle can realize the noncontact measurement of liquid level in closed containers. When designing an ultrasonic Lamb wave sensor, it is vital to thoroughly study and select the optimal wedge size at the front of the sensor. In this paper, firstly, we select the best working mode of Lamb waves according to their propagation dispersion curve in aluminum alloy, and we obtain the best angle of wedge through experiments. Secondly, we study the impact of the size of the wedge block on the results, and we obtain the selection method of wedge block parameters. The evaluations show that, when the frequency-thickness product is 3 MHz·mm, the Lamb waves work in the A1 mode, and the experimental effect is the best. At this time, the incident angle of the ultrasonic wave is 27.39°. The wedge thickness should be designed to avoid the near-field area of the ultrasonic field, and we should choose the length as odd multiples of 1/4 wavelength. The rules obtained from the experiment can effectively select the best working mode for ultrasonic Lamb waves, while also providing a basis for the design of the wedge block size in a Lamb wave sensor.

Design and Reliability Analysis of a Novel Redundancy Topology Architecture.

Topology architecture has a decisive influence on network reliability. In this paper, we design a novel redundancy topology and analyze the structural robustness, the number of redundant paths between two terminal nodes, and the reliability of the proposed topology by using natural connectivity and time-independent and time-dependent terminal pair reliability, k-terminal reliability, and all-terminal reliability comprehensively and quantitatively, and we compare these measures of the proposed topology with AFDX in three scenarios. The evaluations show that in the structural robustness analysis, when no nodes are removed, the natural connectivity of the proposed topology with 10 nodes, 16 nodes, and 20 nodes is 77.8%, 26.95%, and 81.39% higher than that of AFDX, respectively. In the time-independent reliability analysis, when the link reliability is 0.9, terminal pair reliability of the proposed topology with 10 nodes, 16 nodes, and 20 nodes is 5.78%, 17.75%, and 34.65% higher than that of AFDX, respectively; k-terminal reliability is 10.04%, 31.97%, and 53.74% higher than that of AFDX, respectively; and all-terminal reliability is 29.36%, 74.37%, and 107.91% higher than that of AFDX, respectively. In the time-dependent reliability analysis, when the operating time is 8000 h, the terminal pair reliability of the proposed topology with 10 nodes, 16 nodes, and 20 nodes is 3.53%, 10.87%, and 21.08% higher than that of AFDX, respectively; the k-terminal reliability is 6.20%, 19.65%, and 32.58% higher than that of AFDX, respectively; and the all-terminal reliability is 18.25%, 45.04%, and 63.86% higher than that of AFDX, respectively. The proposed topology increases the redundant paths of data transmission. It ensures reliable data transmission and has high robustness and reliability. It provides a new idea for improving the reliability of industrial buses.

Whole-transcriptome analysis of periodontal tissue and construction of immune-related competitive endogenous RNA network.

BACKGROUND: In periodontitis, noncoding RNAs may play a regulatory role in the immune microenvironment through competitive endogenous RNA. We aimed to profile noncoding RNA expression and construct immune-related ceRNA network in periodontitis. METHODS: Five inflamed periodontal tissue and five healthy gingivae were collected for whole-transcriptome sequencing. Differential gene, functional enrichment, and protein-protein interaction network analysis were performed to explore the function of differentially expressed genes. CIBERSORTx was used to analyze level of immune cell infiltration in the periodontal tissue. An immune-related competitive endogenous RNA network was constructed and expression of key regulators in the network was validated. RESULTS: Compared with healthy gingiva, 200 mRNAs, 90 long noncoding RNAs, 65 microRNAs, and 518 circular RNAs were differentially expressed, and cell chemotaxis was significantly enhanced in inflamed periodontal tissue. Immune cell infiltration analysis showed that neutrophils, macrophages M1, T follicular helper cells, and naive B cells were significantly increased in periodontitis. Key regulators including JUN, FOS, THBS1, KLF2, WIF1, were identified and their expression was then validated. CONCLUSION: We constructed an immune-related competitive endogenous RNA network in periodontal tissue, which provided new insights into immune homeostasis in periodontitis and laid a foundation for further study of noncoding RNAs. Key regulators in this network may be promising targets for future periodontitis treatment.

[Study on Parametric Release of Ethylene Oxide Sterilization of Medical Devices].

This study briefly introduces the basic theory of sterilization, the characteristics of ethylene oxide sterilization for medical devices and the key factors about sterilization effectiveness, analyzes and compares three methods used in the product release of medical devices sterilized by ethylene oxide: test for sterility, traditional release and parametric release, and focuses on the theoretical basis, feasibility, validation requirements, advantages and disadvantages of parametric release.

Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma.

Angiogenesis is the process of capillary sprouting from pre-existing vessels and it plays a critical role in the carcinogenic process of lung adenocarcinoma (LUAD). However, the association of angiogenesis regulators with the prognosis and progression of LUAD needs to be further elucidated. In this study, we adopted differential expression analysis, Cox proportional hazards (PH) regression analysis and experimental validation to identify angiogenesis regulators correlated with a poor prognosis, immune infiltration and cancer progression in LUAD. These results showed that the diagnostic and prognostic models based on COL5A2 and EPHB2 served as independent biomarkers with superior predictive ability. The patients in the high-risk group exhibited a worse prognosis in the TCGA cohort (P < 0.001, HR = 1.72, 95% CI 1.28-2.30), GSE310210 cohort (P = 0.005, HR = 2.87, 95% CI 1.46-5.61), and GSE31019 cohort (P = 0.01, HR = 2.14, 95% CI 1.19-3.86) than patients in the low-risk group. The high prognostic risk patients had a higher TMB (P < 0.001); higher fractions of M0 macrophages, neutrophils, NK cells resting, and T cells CD4 memory activated (P < 0.05); and higher expression of immune checkpoints PD-1, PDL-1, PDL-2, and B7H3 (P < 0.001). Patients in the high-risk group were more sensitive to chemotherapeutic drugs and molecular targeted drugs such as cisplatin, doxorubicin, gefitinib, and bosutinib (P < 0.0001). In addition, inhibition of COL5A2 and EPHB2 effectively suppressed the proliferation and migration of LUAD cells. The current study identified angiogenesis regulators as potential biomarkers and therapeutic targets for LUAD and may help to further optimize cancer therapy.

Dual-wavelength demodulation technique for interrogating a shortest cavity in multi-cavity fiber-optic Fabry-Pérot sensors.

This paper demonstrates, for the first time, a novel demodulation technique that can be applied for interrogating a shortest cavity in multi-cavity Fabry-Pérot (F-P) sensors. In this demodulation technique, using an amplified spontaneous emission (ASE) light source and two optical fiber broadband filters, the interference only occurs in a shortest F-P cavity that is shorter than the half of the coherence length. Using a signal calibration algorithm, two low-coherence interference optical signals with similar coherence lengths were calibrated to obtain two quadrature signals. Then, the change in the cavity length of the shortest F-P cavity was interrogated by the two quadrature signals and the arctangent algorithm. The experimental results show that the demodulation technique successfully extracted 1 kHz and 500 Hz vibration signals with 39.28 µm and 64.84 µm initial cavity lengths, respectively, in a multi-cavity F-P interferometer. The demodulation speed is up to 500 kHz, and the demodulation technique makes it possible for multi-cavity F-P sensors to measure dynamic and static parameters simultaneously. The results show that the demodulation technique has wide application potential in the dynamic measurement of multi-cavity F-P sensors.

Protective effects of dexmedetomidine on cerebral ischemia/reperfusion injury via the microRNA-214/ROCK1/NF-κB axis.

BACKGROUND: Cerebral ischemia/reperfusion injury (CIRI) is a complication of surgical procedure associated with high mortality. The protective effect of dexmedetomidine (DEX) on CIRI has been explored in previous works, yet the underlying molecular mechanism remains unclear. Our study explored the protective effect of DEX and its regulatory mechanism on CIRI. METHODS: A CIRI rat model was established using middle cerebral artery occlusion (MCAO). Neurological deficit scores for rats received MCAO modeling or DEX treatment were measured. Cerebral infarction area of rats was detected by TTC staining, while damage of neurons in hippocampal regions of rats was determined by hematoxylin-eosin (HE) staining. Apoptosis rate of neurons in hippocampal regions was examined by TUNEL staining. The dual-luciferase assay was performed to detect the binding of microRNA-214 (miR-214) to Rho-associated kinase 1 (ROCK1). RESULTS: DEX treatment significantly reduced infarction area of MCAO rats and elevated miR-214 expression. Injection of miR-214 inhibitor attenuated the effect of DEX in MCAO rats by increasing the area of cerebral infarction in rats and apoptosis rate of hippocampal neurons. ROCK1 was targeted and negatively regulated by miR-214. The overexpression of ROCK1 led to activation of NF-κB to aggravate CIRI. CONCLUSION: Therapeutic effects of DEX on CIRI was elicited by overexpressing miR-214 and impairing ROCK1 expression and NF-κB activation. Our finding might provide novel insights into the molecular mechanism of DEX in rats with CIRI.

Synthesis and properties of sildenafil isostere.

A series of novel pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and evaluated for their anti-phosphodiesterase-5 (PDE-5) activity. A total of 28 compounds, containing alkyl and aryl groups at the 1-N and 3-C positions on the pyrazole ring, and also bearing different alkyl substituents on the piperazine ring were synthesized. Four compounds (4d, 5d, 6d, and 5o) were found to have better inhibitory activity against PDE-5 (IC50 < 10 nM). All four of the most active compounds contain a phenyl ring at the N1 position. Compounds containing a 3,5-dimethylpiperazinyl group show better activity than others. These results suggest that compound 5o can be used as a lead structure for developing new inhibitors of PDE-5.

Analysis and Validation of Ultrasonic Probes in Liquid Level Monitoring Systems.

Selecting and designing the optimum ultrasonic probe is vital for ultrasonic measurements and experiments. The amplitude of the emitted ultrasonic wave excitation signal as well as the diameter and the natural frequency of the probe seriously affect the validity of the probe results. In this paper, we analyze the significance of the key parameters of the ultrasonic probe theoretically. Further, an external fixed-point liquid level monitoring system was assembled according to the principle of ultrasonic reflection and transmission. On this experimental platform, we study the key parameters of the ultrasonic probe that affect the system evaluation through a simulation and experiment, and select the optimal sensor parameters for this experiment. The evaluations show that under the experimental conditions where the tested container is made of aluminum alloy and its wall thickness is 3 mm, the best results are obtained when the diameter of the ultrasonic sensor is 15 mm, the amplitude of the emitted excitation signal is ±15 V, and the frequency is 1 MHz. The results' average deviation is less than ±0.22 V. The evaluations are consistent with the simulation results. This research can effectively monitor the liquid in the closed, ultra-thin-walled container, and can realize non-contact measurement. It provides an effective basis for the parameters selection and design of the ultrasonic probe in the ultrasonic-based experiments and tests.