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Objective: In this study, we used HepG2 human hepatocellular carcinoma cells to study the effects of Compound Xishu Granule (CXG) on cell proliferation, apoptosis, and the cell cycle in vitro. We also used a xenograft tumor model to study the anti-tumor effects of CXG and related mechanisms in vivo. Methods: The effect of CXG on cell viability was measured using Cell Counting Kit-8 and a colony formation assay. The effect of CXG on apoptosis and the cell cycle was analyzed using flow cytometry. The in vivo anti-tumor effect of CXG was assessed by measuring the volume change in xenograft tumors after drug administration. The CXG anti-tumor mechanism was studied using western blotting assay to detect cell cycle and apoptotic associated proteins. Results: CXG suppressed HepG2 cell proliferation in a time- and dose-dependent manner in vitro. Colony formation experiments showed that CXG administration for 24 h significantly reduced HepG2 cell formations (P

Abstract Background Evidence of hand, foot, and mouth disease (HFMD) in neonates is limited. The aim of this study was to evaluate the clinical symptoms, pathogens, possible transmission routes, and prognosis of neonatal HFMD in Shanghai. Methods This was a case-control study based on the HFMD registry surveillance system. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. Detailed questionnaires, medical history, and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA, and cytokine interleukin (IL-1β, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were measured. All rectal swab specimens were collected and genotyped for enterovirus, and phylogenetic analysis based on the VP1 sequences of coxsackievirus A6 (CV-A6) was performed to investigate molecular and evolutionary characteristics. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to calculate the risk of clinical manifestations in the group of HFMD neonates and their paired siblings. Results There were 16 neonates among the 12,608 diagnosed patients with HFMD, accounting for 0.13%. All neonatal infections were transmitted by other members of the family, mainly the elder siblings, and were caused by CV-A6. CV-A6 was the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD experienced fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. In the elder siblings with HFMD, the proportion of white blood cells was generally higher than in neonates with HFMD. The immunologic function of the neonates with HFMD was basically normal. The levels of inflammatory markers were higher in both neonates and elder siblings with HFMD compared to age-matched controls. The clinical symptoms receded about 1 week after onset. None of the neonates had sequelae. Conclusions In our study, CV-A6 infection in neonates was benign, but had the character of family clustering. Due to the two-child policy in China, elder siblings may be the main route of HFMD transmission.

Abstract Purpose Gardenia blue is one of the natural food additives used in East Asia for many years. Its biosynthesis relies on a key rate-limiting cellulase: β-glucosidase (BGL), which mainly exists in Aspergillus niger (A. niger) cells. The purpose of this study was to obtain active β-glucosidase by cell engineering method and applied to gardenia blue synthesis, which would help to promote the application and reduce the cost of β-glucosidase and gardenia blue. Methods A. niger was identified based on 18S rRNA gene sequencing. β-Glucosidase gene was cloned and expressed based on PCR and prokaryotic expression. The enzyme activity of β-glucosidase was measured based on p-nitrophenyl-β-D-glucopyranoside method. Results An A. niger isolate (AS3.4523) was identified from soil. The β-glucosidase gene of AS3.4523 was cloned and sequenced, which encoded a new type of β-glucosidase mutant containing two specific amino acid substitutions (Asp154Gly and Ser163Pro). Prokaryotic expression of wild-type β-glucosidase in Escherichia coli BL21 showed low cellulase activity (0.29 ± 0.13 U/mL). However, after removing its signal peptide, the β-glucosidase of A. niger AS3.4523 exhibited extremely higher activity (25.88 ± 0.45 U/mL) compared with wild type β-glucosidase (12.59 ± 1.07 U/mL) or other A. niger strains M85 (3.61 ± 0.24 U/mL) and CICC2041 (4.36 ± 0.76 U/mL). Furthermore, recombinant β-glucosidase was applied to geniposide hydrolysis, and gardenia blue pigment was successfully synthesized with the reaction of genipin and Lys. Conclusions This work has discovered a new type of highly active β-glucosidase and provided a theoretical basis for large-scale producing β-glucosidase, which lays a brand-new foundation for gardenia blue preparation with high efficiency and low cost.

Abstract Background Gestational diabetes mellitus (GDM) is now a global health problem. Poor blood glucose control during pregnancy may lead to maternal and neonatal/foetal complications. Recently, the development of information and communication technology has resulted in new technical support for the clinical care of GDM. Telemedicine is defined as health services and medical activities provided by healthcare professionals through remote communication technologies. This study aimed to update the systematic review of the effectiveness of telemedicine interventions on glycaemic control and pregnancy outcomes in pregnant women with GDM. Methods We searched the Web of Science, PubMed, Scopus, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Wan-fang Database, China Biology Medicine and VIP Database for randomized controlled trials (RCTs) related to the effectiveness of telemedicine interventions for GDM from database inception to July 31st, 2019. Languages were limited to English and Chinese. Literature screening, data extraction and assessment of the risk of bias were completed independently by two reviewers. Meta-analysis and trial sequential analysis were conducted in Stata 14.0 and TSA v0.9.5.10 beta, respectively. Results A total of 32 RCTs were identified, with a total of 5108 patients. The meta-analysis showed that telemedicine group had significant improvements in controlling glycated haemoglobin (HbA1c) [mean difference (MD) = − 0.70, P

This paper introduces the working principle of a MEMS safety and arming (S&A) device and measures and tests a setback arming device. To solve the problem of large fabrication errors in the UV-LIGA process, a MEMS S&A fuze device fabricated by low-speed wire electrical discharge machining (EDM) is proposed. Microsprings are susceptible to flexural deformation and secondary deformation in the EDM process, which is solved by setting the auxiliary support beam, using multiple cuts and destress annealing. The linewidth, thickness and elastic coefficient of the microspring fabricated using the EDM process are closer to the designed values than those fabricated using the UV-LIGA process under the same conditions. When comparing the MEMS S&A devices fabricated by the two processes, it is found that the EDM process has a the higher machining accuracy. In view of the plastic deformation of the upper end of the microspring, the structure of the microspring is optimized to incorporate a gradient linewidth, and the optimized setback arming device is tested. The results show that the device can ensure service process safety and launch reliability. The maximum overload that can be withstood in service processing is 17000 g, and the minimum overload for insurance release during launch is 1500 g.

Reactive Oxygen Species (ROS) are present in excess amounts in patients with tumors, and these ROS can kill and destroy tumor cells. Therefore, tumor cells upregulate ROS-related genes to protect them and reduce their destructing effects. Cancer cells already damaged by ROS can be repaired by expressing DNA repair genes consequently promoting their proliferation. The present study aimed to identify the signature genes of and regulating network of ROS-related genes and DNA repair genes in lung adenocarcinoma (LUAD) using transcriptomic data of public databases. The LUAD transcriptome data in the TCGA database and gene expressions from Gene Expression Omnibus (GEO) were analyzed and samples were clustered into 5 ROS-related categories and 6 DNA repair categories. Survival analysis revealed a significant difference in patient survival between the two classification methods. In addition, the samples corresponding to the two categories overlap, thus, the gene expression profile of the same sample with different categories and survival prognosis was further explored, and the connection between ROS-related and DNA repair genes was investigated. The interactive sample recombination classification was used, revealing that the patient's prognosis was worse when the ROS-related and DNA repair genes were expressed at the same time. The further research on the potential regulatory network of the two categories of genes and the correlation analysis revealed that ROS-related genes and DNA repair genes have a mutual regulatory relationship. The ROS-related genes namely NQO1, TXNRD1, and PRDX4 could establish links with other DNA repair genes through the DNA repair gene NEIL3, thereby balancing the level of ROS. Therefore, targeting ROS-related genes and DNA repair genes might be a promising strategy in the treatment of LUAD. Finally, a survival prognostic model of ROS-related genes and DNA repair genes was established (TERT, PRKDC, PTTG1, SMUG1, TXNRD1, CAT, H2AFX, and PFKP). The risk score obtained from our survival prognostic model could be used as an independent prognostic factor in LUAD patients.

Fritillaria species, a well-known Chinese traditional medicine for more than 2,000 years, have become rare resources due to excessive harvesting. In order to balance the economical requirement and ecological protection of Fritillaria species, it is necessary to determine (1) the important environmental variables that were responsible for the spatial distribution, (2) distribution change in response to climate change in the future, (3) ecological niche overlap between various Fritillaria species, and (4) the correlation between spatial distribution and phylogenies as well. In this study, the areas with potential ecological suitability for Fritillaria cirrhosa, Fritillaria unibracteata, and Fritillaria przewalskii were predicted using MaxEnt based on the current occurrence records and bioclimatic variables. The result indicated that precipitation and elevation were the most important environmental variables for the three species. Moreover, the current suitable habitats of F. cirrhosa, F. unibracteata, and F. przewalskii encompassed 681,951, 481,607, and 349,199 km2, respectively. Under the scenario of the highest concentration of greenhouse gas emission (SSP585), the whole suitable habitats of F. cirrhosa and F. przewalskii reach the maximum from 2021 to 2100, while those of F. unibracteata reach the maximum from 2021 to 2100 under the scenario of moderate emission (SSP370) from 2021 to 2100. The MaxEnt data were also used to predict the ecological niche overlap, and thus high overlap occurring among three Fritillaria species was observed. The niche overlap of three Fritillaria species was related to the phylogenetic analysis despite the non-significance (P > 0.05), indicating that spatial distribution was one of the factors that contributed to the speciation diversification. Additionally, we predicted species-specific habitats to decrease habitat competition. Overall, the information obtained in this study provided new insight into the potential distribution and ecological niche of three species for the conservation and management in the future.

Remote sensing has become an indispensable method for estimating the regional-scale collection of grassland aboveground biomass (AGB). However, the lack of ground verification samples often reduces the inversion accuracy. This paper aimed to find a non-destructive method to quickly obtain grassland AGB at quadrat-scale through unmanned aerial vehicles (UAVs) in a large area. Thus, we proposed and assessed the vertical and horizontal indices from UAV RGB images as predictors of grassland AGB using the random forest (RF) machine learning technique. By comparing the performance of different indices combinations, we found that the model combing the horizontal and vertical indices (RFVH) performed best (R2 = 0.78; RMSE = 24.80 g/m2), followed by the model using only horizontal indices (the RFH model; R2 =0.73; RMSE =26.54 g/m2), and the last was the model using only the vertical index. However, the RFVH model was unsuitable for collecting AGB samples in a large area because the UAVs with RGB cameras failed to obtain vegetation height information in areas with high vegetation coverage. In conclusion, the RFH model can be used to replace the traditional destructive method for collecting ground data over large regions for AGB satellite inversion.

In this paper, we clarify the duplicated electromagnetic characteristics between the proposed two-beam overmoded multi-gap structure published in the paper titled “Tractable resonant structure with two nonuniform beams for a high-power 0.22-THz extended interaction oscillator” [Bi et al., IEEE Electron Device Lett. 42(6), 931–934 (2021)] and conventional multi-gap structures from the physical concept point of view. The replacement of the TE10 mode by the TE30 mode used in the interaction gaps provides the basis for the duplicated electromagnetic field distributions and frequencies between the two structures. The concept of magnetic coupling is proposed to support the resonant condition that supports duplication of the TE30 field and the frequency of the single-gap structure into the periodic standing-wave field of the multi-gap structure. With this concept, the perturbation of different axial phase shifts across one period to the standing-wave field of the TE30-0 mode is analyzed to clarify the profiles of the dispersion curves of the TE30 mode in the overmoded structure and the TE10 mode in the conventional structure. To demonstrate the profiles, a 220-GHz overmoded and conventional structure with nine gaps is designed, and their dispersion curves are obtained by using eigenmode simulations. In addition, the effect of the difference in the boundary conditions of the geometries of these two structures on the magnetic field distribution is analyzed to demonstrate the duplication of the ohmic losses between the two structures. The physical analysis in the duplicated electromagnetic characteristics lays a foundation for the promising design of the overmoded structure with two beams for high frequency extended interaction oscillators.

We report on our recently developed method for tracing lines of flux in three-dimensional diffracted wavefields using an approach we call ’non-linear ray tracing’ but which can be more accurately described as tracing the lines of flux in the context of the Eikonal function. These ’rays’ navigate through the diffracted field guided by the derivative of the phase at a sequence of successive points. Our approach is based on the Angular Spectrum method, a numerical algorithm that accurately and efficiently calculates diffracted fields for numerical apertures

Forecasts of numerical weather prediction models unavoidably contain errors, and it is a common practice to post-process the model output and correct the error for the proper use of the forecasts. This study develops a grid-to-multipoint (G2N) model output error correction scheme which extracts model spatial features and corrects multistation forecasts simultaneously. The model was tested for an operational high-resolution model system, the precision rapid update forecasting system (PRUFS) model, running for East China at 3 km grid intervals. The variables studied include 2 m temperature, 2 m relative humidity, and 10 m wind speed at 311 standard ground-based weather stations. The dataset for training G2N is a year of historical PRUFS model outputs and the surface observations of the same period and the assessment of the G2N performance are based on the output of two months of real-time G2N. The verification of the real-time results shows that G2N reduced RMSEs of the 2 m temperature, 2 m relative humidity, and 10 m wind speed forecast errors of the PRUFS model by 19%, 24%, and 42%, respectively. Sensitivity analysis reveals that increasing the number of the target stations for simultaneous correction helps to improve the model performance and reduces the computational cost as well indicating that enhancing the loss function with spatial regional meteorological structure is helpful. On the other hand, adequately selecting the size of influencing grid areas of the model input is also important for G2N to incorporate enough spatial features of model forecasts but not to include the information from the grids far from the correcting areas. G2N is a highly efficient and effective tool that can be readily implemented for real-time regional NWP models.

JHDM1D antisense 1 (JHDM1D-AS1), a long non-coding RNA (lncRNA), has been shown to promote pancreatic cancer growth by inducing an angiogenic response. However, its biological and clinical significance in non-small-cell lung cancer (NSCLC) is still unclear. In this study, we examined the expression and prognostic significance of JHDM1D-AS1 in NSCLC. The effects of JHDM1D-AS1 knockdown or overexpression on NSCLC growth and metastasis were investigated. We show that JHDM1D-AS1 is upregulated in NSCLC relative to adjacent normal lung tissues. High JHDM1D-AS1 expression is significantly correlated with advanced tumor, node, and metastasis (TNM) stage and lymph node metastasis. JHDM1D-AS1 expression serves as an independent prognostic factor for overall survival of patients with NSCLC. Functionally, JHDM1D-AS1 knockdown inhibits NSCLC cell aggressiveness both in vitro and in vivo, which is rescued by ectopic expression of JHDM1D-AS1. JHDM1D-AS1 binding stabilizes DHX15 protein in NSCLC cells. DHX15 overexpression enhances NSCLC cell proliferation and invasion, whereas knockdown of DHX15 exerts opposite effects. JHDM1D-AS1-mediated aggressive phenotype is impaired when DHX15 is silenced. Ectopic expression of DHX15 restores the defects in proliferation and invasion of JHDM1D-AS1-depleted NSCLC cells. Collectively, the interaction between JHDM1D-AS1 and DHX15 accounts for NSCLC growth and metastasis. This work provides potential additional therapeutic targets for treatment of NSCLC. Keywords: DHX15, lncRNA, lung cancer, metastasis, stabilization

Aptamer–drug conjugates (ApDCs) are potential targeted pharmaceutics, but their clinical applications are hampered by fast clearance in blood. Herein we report the construction of ApDCs modified with artificial base F and the study of biological activities. Two types of F-base-modified ApDCs were prepared, Sgc8-paclitaxel by conjugation and Sgc8-gemcitabine, by automated solid-phase synthesis. In vitro experiments showed that F-base-modified ApDCs retain the specificity of the aptamer to target cells and the biological stability is improved. In vivo studies demonstrated that the circulatory time is increased by up to 55 h or longer, as the incorporated F base leads to a stable ApDC-albumin complex as the formulation for targeted delivery. Moreover, conjugated drug molecules were released efficiently and the drug (paclitaxel) concentration in the tumor site was improved. The results demonstrate that an F-base-directed ApDC-albumin complex is a potential platform for drug delivery and targeted cancer therapy.

The burrowing activity of plateau pikas (Ochotona curzoniae; hereafter, pikas) may profoundly influence vegetation species composition on the Qinghai-Tibetan Plateau (QTP). Although significant efforts have been made to examine the relationship between vegetation species composition and pikas disturbance, our knowledge regarding the direct influence of pikas activity on vegetation species diversity is still limited. We conducted field observations on pikas burrows and surrounding vegetation patches at 23 alpine grassland sites to investigate this effect. When compared to vegetation patches, pikas burrowing activity decreased soil hardness, thus improving water infiltration, while caused the less reduction of soil nutrition and soil moisture when compared to adjacent vegetation patches. Vegetation species composition on pikas burrows significantly differed from that on vegetation patches. Common plant species between pikas burrows and vegetation patches were fewer than three in all types of grasslands, and ten species were found exclusively on pikas burrows. The total species richness, including both pikas burrows and vegetation patches, was approximately 1.3–2.5 times higher than that on each single patch type (pikas burrows or vegetation patches). A conceptual framework was proposed to synthesize the evolution of vegetation species composition under a disturbance regime resulting from pika’s burrowing. Overall, we concluded that pika’s burrowing activity enhanced vegetation species richness by loosening the soil, creating safe sites for seed settling and germination, which provided a novel habitat for vegetation invasion.

The resistance to radiotherapy in lung cancer can be attributed to vasculogenic mimicry (VM) to some extent. Celecoxib (CXB), a selective inhibitor of cyclooxygenase-2 (COX-2), is reported as a radiosensitizer in non-small cell lung cancer (NSCLC). However, whether CXB can regulate VM formation via an off-target effect to radiosensitize NSCLC remains unclear. This study aimed to elucidate the mechanism underlying the radiosensitizing effect of CXB on NSCLC, i.e., whether CXB can inhibit VM formation via binding to newly identified targets other than COX-2. CXB radiosensitivity assay was performed in BALB/c mice bearing H460 xenografts and C57 mice bearing Lewis lung cancer (LLC) xenografts, which were divided into the control, CXB, irradiation (IR) treatment, and IR plus CXB groups. VM formation was observed using 3D Matrigel, periodic acid solution (PAS) staining, and immunofluorescence staining. The potential off-targets of CXB were screened using Protein Data Bank (PDB) database, MGLTools 1.5.6, and AutoDock Vina 1.1.2 and confirmed by Western blotting, enzyme activity assay, and RNA interference in vitro experiments and by immunohistochemistry in vivo experiments. CXB treatment almost eliminated the enhancement of VM formation by IR in vitro and in vivo, partially due to COX-2 inhibition. Four potential off-targets were predicted by molecular docking. Among them, aminopeptidase N (APN) and integrin alpha-V (ITAV) were remarkably inhibited in protein expression and enzyme activity in vitro or in vivo, consistent with the remarkable reduction of VM formation in H460 xenografts in BALB/c mice. In conclusion, CXB dramatically blocked VM through inhibiting newly identified off-targets APN and ITAV, other than COX-2, then radiosensitizing NSCLC.

Fractional vegetation cover (FVC) products provide essential data support for ecological environmental monitoring and simulation studies. However, the lack of validation efforts of FVC products limits their applications. Based on Sentinel-2 data and intensive multi-scale measured FVC data, the accuracies of two FVC products (GEOV3 and MuSyQ) in alpine grassland ecosystems were validated through direct validation and multi-scale validation. Based on the heterogeneity of the underlying surface (HUS) of the monitoring plots, the impact of the HUS of the monitoring plots on the product validation was analyzed. The results showed that: (1) the measured data directly validated that the GEOV3 FVC product performed better than the MuSyQ FVC product; (2) the multi-scale validation method based on high-resolution reference FVC map of Sentienl-2 satellite images validated the accuracy of these two FVC products, which was higher than the accuracy directly validated by FVC measured data, leading to overestimation of the validation results; and (3) the HUS of the monitored plots has a significant impact on the FVC product validation. By quantifying the HUS of the monitored plots and removing the heterogeneous monitoring plots, the uncertainty of the validation results can be reduced. It is necessary to consider the impact of validation methods and the HUS on the validation results in future product validation.

Bactrocera dorsalis is a notorious polyphagous pest in China, and its management strategies largely depend on methyl eugenol (ME), which has been widely used as an attractant to monitor and eradicate B. dorsalis populations for seven decades. However, the non-responsiveness levels in field B. dorsalis populations to ME is unknown. In this study, we monitored the response to ME in field populations from the four most heavily infested provinces in China, and the results showed that the populations had lower sensitivity to ME relative to GZS susceptible strain. The percent responsiveness of the lowest sensitivity population was 5.88-, 3.47-, and 1.47-fold lower relative to the susceptible strain at doses of 1, 10, and 100 µL of ME, respectively. Gene expression analysis and inhibitor assays further revealed that odorant binding protein (BdorOBP2, BdorOBP83b) and the P450 enzyme system may be associated with the lower response to ME. To our knowledge, this work is the first to report that the P450 enzyme system confers a lower responsiveness to lure insects. These findings provided valuable insights for exploiting ME non-responsiveness to protect sterile males from ME-based control strategies and the use of lures combined with insecticides.

An optimized multi-step index (MSI) 2-LP-mode fiber is proposed and fabricated with low propagation loss of 0.179 dB/km, low intermodal crosstalk and excellent bend resistance. We experimentally clarified the characteristics of backward Brillouin scattering (BBS) and forward Brillouin scattering (FBS) induced by radial acoustic modes (R0,m) in the fabricated MSI 2-LP-mode fiber, respectively. Via the use of this two-mode fiber, we demonstrated a novel discriminative measurement method of temperature and acoustic impedance based on BBS and FBS, achieving improved experimental measurement uncertainties of 0.2 °C and 0.019 kg/(s·mm2) for optoacoustic chemical sensing. The low propagation loss of the sensing fiber and the new measurement method based on both BBS and FBS may pave the way for long-distance and high spatial resolution distributed fiber sensors.

Radioiodination of oligonucleotides provides an extra modality for nucleic acid-based theranostics with potential applications. Herein, we report the design and synthesis of a phosphoramidite embedded with a phenolic moiety and demonstrate that oligonucleotides can be readily functionalized with phenol as a precursor by general DNA synthesis. It was identified that the introduction of the precursor does not block the specificity of an aptamer, and the radioiodination is applicable to both DNA and RNA oligonucleotides in a site-specific approach with a commercial kit.

BackgroundP16 methylation is expected to be potential diagnostic and therapeutic targets for esophageal cancer (EC). The intratumoral heterogeneity (ITH) of EC has been mentioned but has not been quantitatively measured yet. We aimed to clarify the impact of ITH on pathological diagnosis and P16 methylation, and the concordance between endoscopic biopsy and the corresponding surgically resected tissue.MethodsWe designed a systematic sampling method (SSM) compared with a general sampling method (GSM) to obtain EC tumor tissue, tumor biopsy, and normal squamous epithelium biopsy. MethyLight assay was utilized to test P16 methylation. All specimens obtained by the SSM were pathologically diagnosed.ResultsA total of 81 cases were collected by the GSM, and 91.4% and 8.6% of them were esophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EADs), respectively. Nine SSM cases were 100.0% ESCCs. The positive rates of P16 methylation of the GSM tumor and normal tissues were 63.0% (51/81) and 32.1% (26/81), respectively. For SSM samples, tumor tissues were 100.0% (40/40) EC and 85.0% (34/40) P16 methylated; tumor biopsy was 64.4% (29/45) diagnosed of EC and 68.9% P16 methylated; the corresponding normal biopsies were 15.7% (8/51) dysplasia and 54.9% (28/51) P16 methylated. The concordance of pathological diagnosis and P16 methylation between tumor biopsy and the corresponding tumor tissue was 75.0% and 62.5%, respectively.ConclusionThe SSM we designed was efficient in measuring the ITH of EC. We found inadequate concordance between tumor biopsy and tissue in pathological diagnosis and P16 methylation.

Ischemia-reperfusion (I/R) injury is detrimental to cardiovascular system. Alteration in glucose metabolism has been recognized as an important adaptive response under hypoxic conditions. However, the biological benefits underlying this metabolic phenotype remain to be elucidated. This study was designed to investigate the impact of hypoxic acclimation (HA) on cardiac I/R injury and the antioxidative mechanism(s). Male adult mice were acclimated in a hypoxic chamber (10% oxygen [O2]) for 8 h/day for 14 days, and then subjected to cardiac I/R injury by ligation of left anterior descending coronary artery for 30 min and reperfusion for 24 h or 7 days. Our results showed that HA attenuated oxidative stress and reduced infarct size in the I/R hearts. This cardioprotective effect is coupled with an elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification partially due to inflammatory stimulation. Hyperglycosylation activated glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme in the pentose phosphate pathway, resulting in an upregulation of NADPH/NADP+ and GSH/GSSG couples and enhancement of redox homeostasis in the heart. Pharmacological suppression of O-GlcNAcylation totally abolished the influence of HA on the G6PDH activity, redox balance and post-I/R damage in the hearts and cultured cardiomyocytes, whereby augmentation of O-GlcNAcylation further enhanced the benefits, suggesting a central role of O-GlcNAcylation in HA-initiated antioxidative and cardioprotective effects. These findings, therefore, identified HA as a promising anti-I/R strategy for the heart and proposed O-GlcNAc modification of G6PDH as a therapeutic target in ischemic heart disease.

Abstract In the field of three‐dimensional (3D) cell culture and tissue engineering, great advance focusing on functionalized materials and desirable culture systems has been made to mimic the natural environment of cells in vivo. Mechanical loading is one of the critical factors that affect cell/tissue behaviors and metabolic activities, but the reported models or detection methods offer little direct and real‐time information about mechanically induced cell responses. Herein, for the first time, a stretchable and multifunctional platform integrating 3D cell culture, mechanical loading, and electrochemical sensing is developed by immobilization of biomimetic peptide linked gold nanotubes on porous and elastic polydimethylsiloxane. The 3D scaffold demonstrates very good compatibility, excellent stretchability, and stable electrochemical sensing performance. This allows mimicking the articular cartilage and investigating its mechanotransduction by 3D culture, mechanical stretching of chondrocytes, and synchronously real‐time monitoring of stretch‐induced signaling molecules. The results disclose a previously unclear mechanotransduction pathway in chondrocytes that mechanical loading can rapidly activate nitric oxide signaling within seconds. This indicates the promising potential of the stretchable 3D sensing in exploring the mechanotransduction in 3D cellular systems and engineered tissues.

Allergic diseases are significant diseases that affect many patients worldwide. In the past few decades, the incidence of allergic diseases has increased significantly due to environmental changes and social development, which has posed a substantial public health burden and even led to premature death. The understanding of the mechanism underlying allergic diseases has been substantially advanced, and the occurrence of allergic diseases and changes in the immune system state are known to be correlated. With the identification and in-depth understanding of innate lymphoid cells, researchers have gradually revealed that type 2 innate lymphoid cells (ILC2s) play important roles in many allergic diseases. However, our current studies of ILC2s are limited, and their status in allergic diseases remains unclear. This article provides an overview of the common phenotypes and activation pathways of ILC2s in different allergic diseases as well as potential research directions to improve the understanding of their roles in different allergic diseases and ultimately find new treatments for these diseases.

Vegetation patch patterns, which are used as indicators of state, functionality, and catastrophic changes in the arid ecosystem, have received much attention. However, little is known about the controlling factors and indicators that underlie vegetation patch patterns in the alpine grassland ecosystem. Here, we firstly studied characteristics of vegetation patch patterns with aerial photography by using an unmanned aerial vehicle and evaluated the vegetation patch-size distribution with power law (PL) and truncated power law (TPL) models on the central part of the Qinghai-Tibetan Plateau (QTP). We then investigated the effects of environmental factors and biotic disturbances on vegetation patch patterns. The results showed that (1) there were four typical vegetation patch patterns, i.e. spot, stripe, sheet, and uniform patterns; (2) soil water content and air temperature were major environmental factors affecting vegetation patch patterns; (3) biotic disturbance of plateau pika (Ochotona curzoniae) affected vegetation patch patterns by changing the number, area, and connectivity of vegetation patches; and (4) vegetation patch-size distribution parameters were significantly related to soil hydrothermal variables (P

This study aimed to investigate the association of vegetable and fruit consumption with carotid plaque (CP) and carotid intima-media thickness (CIMT), two predictors of carotid atherosclerosis, within urban and rural adults at high risk of developing cardiovascular diseases (CVDs) in regional China. A total of 11,392 adults at high CVD risk were identified from general population of 71,511 in this cross-sectional study, conducted between November of 2015 and May of 2016 in the Jiangsu Province. Among these 11,392 high risk participants, CP prevalence was 36.7%. The independent variables, vegetable and fruit intake frequency, were assessed by a food frequency questionnaire. The outcome variables, CIMT and CP, were measured by ultrasound examination. The ANCOVA analysis showed no association between CIMT values and vegetable and fruit intake frequencies. Multivariate logistic regression models were introduced to examine the association between vegetable and fruit intake and CP. After adjustment for potential confounders, the odds ratios (ORs) for participants who occasionally and daily consumed vegetable to experience any CP were 0.67 (95%CI: 0.58-0.78) and 0.70 (95%CI: 0.62-0.79), respectively, compared with those rarely consumed vegetable. While the adjusted ORs were 0.77 (95%CI: 0.64-0.92) and 0.80 (95%CI: 0.68-0.94), separately, for occasional and daily vegetable consumers to develop single CP relative to their counterparts who rarely consumed any vegetables. However, no significant association between fruit consumption and CP was observed. Among the Chinese population at high CVD risk, consumption of fresh vegetables was negatively associated with the risk of developing carotid plaque.

Abstract We wanted to determine whether subjective sleep disturbance was associated with serum glycated hemoglobin (HbA1c) in people with type 2 diabetes mellitus. In total, 944 randomly-selected people with diabetes completed the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). Participants’ glycaemia was assessed using HbA1c in March 2016 and September 2017. The PSQI score and the change in score(△PSQI), and the HbA1c and its change (△HbAlc) were analysed by sex and age (30–45, 46–60, 61–75, and 76–89 years). Associations between time point PSQI and △PSQI with static HbA1c and △HbA1c were analysed using multiple linear regression. The results showed subjective sleep disturbance among people with diabetes was not correlated with serum HbAlc (β coefficient = 0.032, P = 0.103). However, cross-sectional multiple linear regression showed the relationship was present in women (β coefficient = 0.163, P

Echinochloa crus-galli is a major weed in rice fields in China, and quinclorac has been long used for its control. Over-reliance of quinclorac has resulted in quinclorac resistance in E. crus-galli. Two resistant (R) E. crus-galli populations from Hunan, China were confirmed to be at least 78-fold more resistant to quinclorac than the susceptible (S) population. No difference in foliar uptake of 14C-labelled quinclorac was detected between the R and S plants. However, a higher level of 14C translocation and a lower level of quinclorac metabolism were found in the R plants. Basal and induced expression levels of β-cyanoalanine synthase (β-CAS) gene and β-CAS activity were not significantly different between the R and S plants. However, the induction expression of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO1) gene by quinclorac treatment was evident in the S plants but not in the R plants. Quinclorac resistance in the two resistant E. crus-galli populations was not likely to be related to foliar uptake, translocation or metabolism of quinclorac, nor to cyanide detoxification via β-CAS. Thus, target-site based quinclorac signal reception and transduction and regulation of the ethylene synthesis pathway should be the focus for further research. Keywords: Echinochloa crus-galli, Quinclorac resistance, Quinclorac metabolism, β-cyanoalanine synthase, 1-aminocyclopropane-1-carboxylic acid synthase, 1-aminocyclopropane-1-carboxylic acid oxidase, Rice

AIM: To study whether specific anesthetic drugs or tear layer evaporation was primarily responsible for the acute cataract and what the change of lens structure is in anesthetized mice. METHODS: Five groups were set up in the experiment: Group A (topicamide and phenylephrine mixed eye drop+ chloral hydrate), Group B (tropicamide and phenylephrine mixed eye drop+sevoflurane), Group C (tropicamide and phenylephrine mixed eye drop), Group D (topicamide and phenylephrine mixed eye drop+chloral hydrate, carbomer eye drop in the right eyes), and Group E (tropicamide and phenylephrine mixed eye drop+sevoflurane, carbomer eye drop in the right eyes). A simple classification system was used to assess the severity of lens opacity. And a numerical value from 0 to 3 to each grade was assigned for the cataract index calculation and data analysis. The gross appearance and time course of development of lens opacity were assessed. Hematoxylin and eosin staining was used to observe the lens structure changes in the reversible cataract. RESULTS: Tropicamide did not induce lens opacification in mice. Lens opacity caused by inhaled sevoflurane was similar to injected cholral hydrate. Both inhaled-anesthetic-induced lens opacity and injected-anesthetic-induced lens opacity could be prevented by carbomer eye drop. In the severe opacity lens, a wide range of lens fiber cell structure had disordered. The fiber cells became uneven thickness. CONCLUSION: The acute reversible lens opacity can unilaterally develop or be induced by a local cause. The structure of lens fiber cells changed in the lens opacity which may influence the permanent connection of the lens fiber cells. This study was not only of practical significance to help maintain lens transparency for eye research, but also of the deeper consideration about the reversible lens opacification phenomenon.

AIM: To investigate the protective effects of gigantol on aldose reductase(AR)pathway and oxidative stress induced by high glucose in human retinal microvascular endothelial cells(HRMECs).METHODS: HRMECs were cultured and divided into the five groups: normal glucose group, mannitol group,high glucose group, gigantol group and epalrestat group. Cell vitality was detected by the MTS assay, reactive oxygen species(ROS)levels were detected by DCFH-DA fluorescent probe, protein expressions of nuclear factor kappa B(NF-κB)were observed by Western blotting, mRNA levels of AR, hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)were measured by qRT-PCR.RESULTS: DCFH-DA fluorescent probe levels showed that gigantol reduced ROS generation obviously, and protein expressions of NF-κB, mRNA expressions of AR,HIF-1α and VEGF were all decreased. The expression trends of AR and NF-κB in epalrestat group were consistent with gigantol group.CONCLUSION: Gigantol and epalrestat could inhibit the activation of AR/NF-κB pathway, and gigantol also could inhibit high glucose induced oxidative stress and in HRMECs, which may have a protective effect on diabetic retinopathy(DR), and improve angiogenesis.

To make up for the deficiencies in the present method of measuring microdetonator output energy, this paper uses PVDF (Polyvinylidene Fluoride) piezoelectric films as sensors and designs a system to test the output pressure of microdetonators with a 2.5 mm diameter. The average measured output pressure was 9.87GPa. In addition, detonation tests were carried out which showed that a microdetonator with a 10 mg charge could reliably detonate a JO-9C(III model) lead explosive with an 8 mg charge in a 0.7 mm air-gap. The detonation simulations for lead explosives using LS-DYNA software were consistent with the detonation test results. There was less than 5% error between the output pressure values and the test values of microdetonators. The results showed that PVDF piezoelectric films have rapid response times, high precision and low production cost in output pressure tests. The simulation model has practical significance for the quantitative evaluation of microdetonator output energy.

The manufacturing process of planar microsprings by the UV-LIGA process was introduced; the mechanism of fabrication error was analyzed from three process stages of exposure, SU-8 swelling, and corrosion; and the corresponding improvement measures were proposed. The line width of two groups of microsprings after the exposure, SU-8 swelling, and debonding was measured, and the elastic coefficients in three coordinate directions were accurately measured. The results show that the factors that affect the line width error are stable. The effects of the exposure diffraction, swelling of SU-8 glue, and debonding corrosion process on the line width size follow the order: corrosion error > swelling error > exposure error. When the line width is small, the aspect ratio of the microspring is large, and the direction of machining error is generally negative. The relative error of the elastic coefficient of microsprings in three coordinate directions is larger. The influence rule of the line width error on the elastic coefficient follows the order: kerrory > kerrorx > kerrorz.

Increasing knowledge of the relationship between cancer and dysregulated polyamine catabolism suggests interfering with aberrant polyamine metabolism for anticancer therapy that will have considerable clinical promise. SMO (spermine oxidase) plays an essential role in regulating the polyamines homeostasis. Therefore, development of SMO inhibitors has increasingly attracted much attention. Previously, we successfully purified and characterised SMO. Here, we presented an in silico drug discovery pipeline by combining pharmacophore modelling and molecular docking for the virtual screening of SMO inhibitors. In vitro evaluation showed that N-(3-{[3-(dimethylamino)propyl]amino}propyl)-8-quinolinecarboxamide (SI-4650) inhibited SMO enzyme activity, increased substrate spermine content and reduced product spermidine content, indicating that SI-4650 can interfere with polyamine metabolism. Furthermore, SI-4650 treatment suppressed cell proliferation and migration. Mechanistically, SI-4650 caused cell cycle arrest, induced cell apoptosis, and promoted autophagy. These results demonstrated the properties of interfering with polyamine metabolism of SI-4650 as a SMO inhibitor and the potential for cancer treatment.

To solve the structural strength problem of a MEMS arming device for a fuze, a kind of arming device applied to a certain type of 40 mm grenade is designed. This paper introduces the working principle of the arming device; simulates the shear pin, rotary pin and locking mechanism in the device; designs a variety of different test tools for test verification; and further increases the explosion reliability and arming safety tests. The results show that the arming device improves the structural strength and can meet the action requirements of a certain type of 40 mm grenade for safety release, as well as the application requirements of explosion reliability and arming safety.

Fatigue failure is invariably the most crucial failure mode for metallic structural components. Most microstructural strategies for enhancing fatigue resistance are effective in suppressing either crack initiation or propagation, but often do not work for both synergistically. Here, we demonstrate that this challenge can be overcome by architecting a gradient structure featuring a surface layer of nacre-like nanolaminates followed by multi-variant twinned structure in pure titanium. The polarized accommodation of highly regulated grain boundaries in the nanolaminated layer to cyclic loading enhances the structural stability against lamellar thickening and microstructure softening, thereby delaying surface roughening and thus crack nucleation. The decohesion of the nanolaminated grains along horizonal high-angle grain boundaries gives rise to an extraordinarily high frequency (≈1.7 × 103 times per mm) of fatigue crack deflection, effectively reducing fatigue crack propagation rate (by 2 orders of magnitude lower than the homogeneous coarse-grained counterpart). These intriguing features of the surface nanolaminates, along with the various toughening mechanisms activated in the subsurface twinned structure, result in a fatigue resistance that significantly exceeds those of the homogeneous and gradient structures with equiaxed grains. Our work on architecting the surface nanolaminates in gradient structure provides a scalable and sustainable strategy for designing more fatigue-resistant alloys.

The purpose of this work was to investigate a novel aqueous dispersion (Eudragit® L100-55) f or e nteric c oating o f drugs. Three different casting solutions, Eudragit® L100-55 aqueous dispersion, Eudragit® L 100-55 o rganic s olution, and Eudragit® L30D-55 aqueous dispersion, were used to prepare free films by the casting method. Drug-loaded pellets, prepared by the extrusion-spheronization method, were coated with one of these three coating solutions using the fluidized-bed spray coating technology. Properties of the free films were thoroughly investigated. Films formed by Eudragit® L100-55 aqueous dispersions showed similar properties to those formed by Eudragit® L100-55 organic solution regarding thermodynamic properties, moisture permeability, solubility and acid tolerance ability. Furthermore, the performance of the novel film was better than that formed by Eudragit® L30D-55 aqueous dispersion. Among the three enteric coating solutions, Eudragit® L100- 55 aqueous dispersion will be a promising aqueous dispersion for enteric coating and can be used in the development of enteric-coated preparations.

Background/Aims: Lipid droplets (LDs) are dynamic organelles that store neutral lipids during times of energy excess, and an increased accumulation of LDs in the liver is closely linked to hepatic steatosis. Our previous studies suggested that resveratrol (RSV) supplement could improve hepatic steatosis, but the underlying mechanism, particularly which related to LD accumulation, has not yet been elucidated. Methods: A high-fat diet (HFD) and palmitic acid were used to induce hepatic steatosis in mouse liver and hepatocytes, respectively. The effects of RSV on LD accumulation were analyzed in vivo and in vitro. The effects of RSV on the expression levels of LD-associated genes (ATF6, Fsp27β/CIDEC, CREBH, and PLIN1) were measured by qRT-PCR and western blot assays, followed by KD or overexpression of SIRT1 and ATF6 with small interfering RNAs or overexpressed plasmids, respectively. The dual luciferase reporter assay, chromatin immunoprecipitation assay, coimmunoprecipitation, and proximity ligation assay were utilized to clarify the mechanism of transcriptional regulation and possible interaction between SIRT1 and ATF6. Results: There was a significant increase in the accumulation of LDs in liver and hepatocytes during the process of HFD-induced steatosis, respectively, which was significantly inhibited by RSV supplementation. RSV notably activated SIRT1 expression and decreased the expression levels of ATF6, Fsp27β/CIDEC, CREBH, and PLIN1, which are associated with LD accumulation. Interestingly, the inhibitory effects of RSV on LD accumulation and the associated expression of genes in hepatocytes were abrogated or strengthened with SIRT1 silencing or overexpression, respectively. On the contrary, the benefits of RSV in hepatocytes were eliminated or aggravated when transfected with the overexpressed ATF6 or ATF6 siRNA, respectively. Furthermore, we found that RSV stimulated SIRT1 expression significantly, which was followed by increased deacetylation and inactivation of ATF6, resulting in a positive feedback loop for SIRT1 transcription associated with ATF6 binding to the SIRT1 promoter region. Conclusion: Taken together, these findings indicate that RSV supplementation improves hepatic steatosis by ameliorating the accumulation of LDs, and this might be partially mediated by a SIRT1/ATF6-dependent mechanism.

AIM: To study the effects of FOXO4 on oxidative stress and apoptosis of retinal vascular endothelial cells under high glucose environmental conditions. METHODS: Human retinal vascular endothelial cells were cultured with high glucose medium. Real-time PCR and Western blot were used to detect the expressions of FOXO4 within cells; meanwhile, both FOXO4 RNAi lentivirus and control vector lentivirus were infected the retinal vascular endothelial cells cultured in high sugar culture medium. Real-time PCR and Western blot techniques were used to detect the interference efficiency. After collection of supernatant and cells treated with various interferences, the SOD activity, MDA content in the supernatants and ROS level within cells were detected. Flow cytometry was used to determine the changes of cell apoptosis. Western blot was used to detect the expressions of apoptotic protein cleaved Caspase-3 and cleaved Caspase-9 within cells. RESULTS: The expression of FOXO4 was increased in retinal vascular endothelial cells after treatment with high glucose medium. FOXO4 RNAi lentivirus infection reduced the expression level of FOXO4 in retinal vascular endothelial cells under high glucose environmental conditions. By contrast, control vector lentivirus had no effect on FOXO4 expression in cells. High glucose induced elevated levels of ROS in retinal vascular endothelial cells, reduced the activity of SOD in cell culture medium, increased the content of MDA, elevated the rate of apoptosis, and promoted the expressions of cleaved Caspase-3 and cleaved Caspase-9 proteins in cells. After down-regulation of FOXO4 expression, retinal endothelial cells were induced by high glucose, the activity of SOD in the cell culture medium increased, the levels of MDA, ROS, apoptosis, and the levels of cleaved Caspase-3 and cleaved Caspase-9 proteins decreased in cells as compared with those of retinal vascular endothelial cells. Moreover, compared with those did not interfere with FOXO4 expression, there was statistically significant differences(PCONCLUSION: High glucose induces the expression of FOXO4 in retinal vascular endothelial cells. Knocking-down of FOXO4 expression reduces oxidative stress and apoptosis induced by high glucose medium.

Cancer immunotherapy works by stimulating and strengthening the body’s anti-tumor immune response to eliminate cancer cells. Over the past few decades, immunotherapy has shown remarkable efficacy in the treatment of cancer, particularly the success of immune checkpoint blockade targeting CTLA-4, PD-1 and PDL1, which has led to a breakthrough in tumor immunotherapy. Tumor neoantigens, a new approach to tumor immunotherapy, include antigens produced by tumor viruses integrated into the genome and antigens produced by mutant proteins, which are abundantly expressed only in tumor cells and have strong immunogenicity and tumor heterogeneity. A growing number of studies have highlighted the relationship between neoantigens and T cells’ recognition of cancer cells. Vaccines developed against neoantigens are now being used in clinical trials in various solid tumors. In this review, we summarized the latest advances in the classification of immunotherapy and the process of classification, identification and synthesis of tumor-specific neoantigens, as well as their role in current cancer immunotherapy. Finally, the application prospects and existing problems of neoantigens were discussed.

The goal of this study is to further develop a multi-modality eye imaging system and evaluate its feasibility of acquiring images of different modalities simultaneously. An integrated multimodality imaging system combining spectral-domain optical coherence tomography (SD-OCT), photoacoustic microscopy (PAM), and fluorescence microscopy (FM) was developed, and its performance for eye imaging was validated on multiple clinically-relevant retinal disease models in vivo in rabbits. OCT imaging allows for visualization of the different anatomic retinal layers with high axial resolution. PAM can be used to image vasculature, angiogenesis, and hemorrhages. The leakage of neovascularization can be verified with FM and fluorescein dye. Simultaneous imaging with OCT, PAM, and FM ensures co-registration of the three modalities without being affected by motion artifacts caused by breathing, body or eye movements, and heartbeat. This simultaneous multi-modality eye imaging system could be a new tool for applications both in ophthalmology and other fields.

Patulin (PAT) is a mycotoxin, with several acute, chronic, and cellular level toxic effects, produced by various fungi. A limit for PAT in food of has been set by authorities to guarantee food safety. Research on PAT in tea has been very limited although tea is the second largest beverage in the world. In this paper, HPLC−DAD and GC−MS methods for analysis of PAT in different tea products, such as non-fermented (green tea), partially fermented (oolong tea, white tea, yellow tea), completely fermented (black tea), and post-fermented (dark tea and Pu-erh tea) teas were developed. The methods showed good selectivity with regard to tea pigments and 5-hydroxymethylfurfural (5-HMF) and a recovery of 90–102% for PAT at a 10–100 ppb spiking level. Limit of detection (LOD) and limit of quantification (LOQ) in tea were 1.5 ng/g and 5.0 ng/g for HPLC−UV, and 0.25 ng/g and 0.83 ng/g for GC−MS. HPLC was simpler and more robust, while GC−MS showed higher sensitivity and selectivity. GC−MS was used to validate the HPLC−UV method and prove its accuracy. The PAT content of 219 Chinese tea samples was investigated. Most tea samples contained less than 10 ng/g, ten more than 10 ng/g and two more than 50 ng/g. The results imply that tea products in China are safe with regard to their PAT content. Even an extreme daily consumption of 25 g of the tea with the highest PAT content (124 ng/g), translates to an intake of only 3 μg/person/day, which is still an order of magnitude below the maximum allowed daily intake of 30 µg for an adult.

The sudden outbreak of COVID-19 rapidly developed into a global pandemic, which caused tens of millions of infections and millions of deaths. Although SARS-CoV-2 is known to cause COVID-19, effective approaches to detect SARS-CoV-2 using a convenient, rapid, accurate, and low-cost method are lacking. To date, most of the diagnostic methods for patients with early infections are limited to the detection of viral nucleic acids via polymerase chain reaction (PCR), or antigens, using an enzyme-linked immunosorbent assay or a chemiluminescence immunoassay. This study developed a novel method that uses localized surface plasmon resonance (LSPR) sensors, optical imaging, and artificial intelligence methods to directly detect the SARS-CoV-2 virus particles without any sample preparation. The virus concentration can be qualitatively and quantitatively detected in the range of 125.28 to 106 vp/mL through a few steps within 12 min with a limit of detection (LOD) of 100 vp/mL. The accuracy of the SARS-CoV-2 positive or negative assessment was found to be greater than 97%, and this was demonstrated by establishing a regression machine learning model for the virus concentration prediction (R2 > 0.95).

The theoretical analysis and the experiment of perturbation techniques to the quantitative measurement of electric field characteristics in a 94 GHz extended interaction resonant cavity (EIRC) are described. Parameters such as the observed reflection coefficient (S11) and resonant frequency at the disturbance point can be adopted to determine the Q-factor, relative electric field intensity, and distribution of the EIRC. In the experiment stage, the frequency deviation characteristics of the tested EIRC under the influence of the metallic sphere are consistent with the simulation results, and the relative error of the frequency deviation is 4.40%. This provides an effective solution for studies of the performance monitoring of millimeter–submillimeter-wave electronic devices and the exploration of high-frequency material science.

Objectives To investigate whether dl-3-n-butylphthalide (NBP) affects cholinergic system function and ameliorates cognitive decline in a rat model of vascular dementia (VaD). Methods The VaD rat model was established by bilateral common carotid artery ligation (two-vessel occlusion, 2VO). Rats were divided into five groups: control, sham, 2VO, 2VO+NBP (80 mg/kg; intragastric), and 2VO+donepezil (1 mg/kg; intragastric). Treatments were administered once daily for 2 weeks from day 21 post-surgery. Spatial learning and memory were evaluated by Morris water maze performance. Hippocampal choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular acetylcholine transporter (VAChT), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) expressions were detected using immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction methods. Results The daily escape latency was significantly longer in 2VO rats than in the sham or control groups, while the time spent in the target quadrant was significantly shorter. The daily escape latency of the 2VO+NBP group was significantly shorter compared with the 2VO group. Following NBP treatment, ChAT, AChE, VAChT, and BDNF expressions were significantly upregulated in the hippocampus. Conclusions Central cholinergic dysfunction may be involved in VaD pathogenesis. NBP treatment significantly improved spatial learning and memory in VaD rats, and may enhance cholinergic system function via BDNF-mediated neuroprotection.

To confirm the relationship between sex and the progression of Coronavirus Disease-19 (COVID-19), and its potential mechanism, among severe patients. For this retrospective study, we included 168 consecutive severe patients with pathogen-confirmed COVID-19 who were hospitalized between January 16th and February 4th, 2020, at Tongji Hospital in Wuhan, China. Clinical characteristics, laboratory parameters, and outcomes were compared and analyzed between males and females. In the present study, we analyzed 168 severe patients with COVID-19, including 86 males and 82 females, and 48 patients (28.6%) were diagnosed as critically ill. Of 86 male patients, 12.8% (11/86) died and 75.6% (65/86) were discharged; of 82 female patients, 7.3% (6/82) died and 86.6% (71/82) were discharged. Eleven laboratory parameters showed significant differences between male and female patients, and six of them were higher during the whole clinical course in patients who died than in patients who were discharged. In adjusted logistic regression analysis, males with comorbidities presented a higher risk of being critically ill than males without comorbidities (OR = 3.824, 95% CI = 1.279-11.435). However, this association attenuated to null in female patients (OR = 2.992, 95% CI = 0.937-9.558). A similar sex-specific trend was observed in the relation between age and critically ill conditions. We highlighted sex-specific differences in clinical characteristics and prognosis. Male patients appeared to be more susceptible to age and comorbidities. Sex is an important biological variable that should be considered in the prevention and treatment of COVID-19.

This paper introduces the working principle of a MEMS safety and arming (S&A) device for a fuze that is installed perpendicular to the axis of the projectile. Additionally, the application of low-speed wire electrical discharge machining (EDM) in the fabrication of the device is proposed. Microsprings are susceptible to flexural deformation and secondary deformation in the EDM process, a problem that is solved by designing the auxiliary support beam, using multiple cuts, destress annealing and optimizing the processing parameters. The difficult problem of setback slider deformation in the principle prototype test is properly solved by establishing V-shaped grooves at both ends of the setback slider. The connection mode between the microspring and the frame is changed to a clearance fit connection. The improved setback arming device can guarantee service process safety and launch reliability. The maximum overload that can be withstood in service processing is 20,000 g, and the minimum overload for safety release during launch is 12,000 g. The results show that the EDM process can greatly reduce the machining cost while improving the machining precision and machining speed, which can compensate for the defects of the current manufacturing technology.

Abstract Background Extracellular matrix (ECM) is a mediator of tumor progression. However, whether the alterations of the intraperitoneal ECM prior to tumor establishment affects the malignant progression of ovarian cancer remains elusive. Methods Apolipoprotein (ApoE) knock-out mice was used to analyze the intraperitoneal ECM alterations by quantification of the major components of ECM. ID8 cells were implanted in vivo to generate allografts and human ovarian cancer cell lines were characterized in vitro to assess the effects of ECM alterations on the malignant progression of ovarian cancer. Adhesion assay, immunochemistry, cytokines profile, proliferation assay, transwell invasion assay and western blot were used to determine the malignant phenotype of ovarian cancer cells. Results ApoE loss induced increased ECM deposition, which stimulated the adhesions of ovarian cancer cells. The adhesion-mediated focal adhesion kinase (FAK) signaling enhanced the invasive behaviors of ovarian cancer cells through activation of a ERK-MMP linkage. This ECM-induced signaling cascade was further confirmed in human ovarian cancer cell lines in vitro. Furthermore, reversal of the ECM accumulation with BAPN or abrogation of adhesion-induced ERK activation in ovarian cancer cells with MEK inhibitors (MEKi) was found to effectively delay ovarian cancer progression. Conclusions These findings identify the FAK-ERK activation in cell/matrix adhesion in the malignant progression of ovarian cancer and the efficiency of BAPN or MEKi for tumor suppression, providing an impetus for further studies to explore the possibility of new anticancer therapeutic combinations.