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This study established a ferric ion (Fe3+) detection method as a result of the fluorescence quenching effect of Fe3+ on carbon dots (CDs). Specifically, we proposed, a green microwave synthesis route towards fluorescent CDs that requires only the brewer’s spent grain as starting materials. Transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectra and X-ray photoelectron spectroscopy were performed to investigate the CDs characteristic: morphology, size distribution, functional groups, and composition, respectively. The experimental results, which were run under optimal experimental conditions, indicated that the fluorescence intensity and concentration of Fe3+ were within the desired linear range (0.3–7 μM). The detection limit of this assay towards Fe3+ was 95 nM. The proposed method showed significant selectivity with respect to interfering ions. We evaluated the potential application of this method with tap water, lake water and fetal bovine serum as real samples. Additionally, the CDs could be served as superior bioimaging probes in Hela cells as a result of their excellent optical stability and good biocompatibility. In a word, the present study provides a new idea for CDs derived from the waste of agricultural products for detecting food or environmental contaminants and cell imaging.

Abstract Background Medical education is widely known to be a demanding process that may cause various mental health problems, such as burnout, which can lead to lowered levels of life satisfaction among medical students. Research shows that empathy is negatively correlated with burnout, but there are few studies on the relationship among empathy, burnout and life satisfaction in medical students. The objective of the present study is to explore the correlations of empathy and burnout with life satisfaction and the associated socio-demographic factors among Chinese undergraduate medical students. Methods In this cross-sectional study, 1271 undergraduate medical students (age 19.42 ± 1.34 years, 36% male) from 1st to 4th grades completed questionnaires including the Interpersonal Reactivity Index Chinese version (IRI-C), the Maslach Burnout Inventory Modified Chinese version (MBI-MC), the Satisfaction With Life Scale (SWLS) and socio-demographic characteristics. Statistical analyses included Student’s t-test, one-way ANOVA, post hoc Bonferroni tests, hierarchical linear regression analysis and general linear model-univariate full factorial model. Results Over four academic years, medical students’ empathy levels declined, but their burnout levels almost plateaued and their life satisfaction levels witnessed an initial fall before a rebound. Empathy was correlated with students’ age and grade, and burnout was associated with students’ maternal education. Significant differences in life satisfaction were detected with regard to medical students’ age, academic year, the number of children in the family, place of residence and parents’ educational levels. Conclusions Empathy explained 0.6% of the variance in life satisfaction in contrast to 13.7% of the variance explained by burnout in life satisfaction. Although empathy did not have a main effect on life satisfaction, there was an interaction effect of empathy and burnout on life satisfaction among students of high and low empathy and burnout levels. Students with high levels of empathy and low levels of burnout were most satisfied with life. Medical institutions and related authorities need to find effective measures to enhance students’ empathy levels and reduce burnout to improve their life satisfaction.

For distributed energy system, multi-energy sources and their comprehensive utilization are popularly concerned nowadays. In this paper, optimal operation of a multi-energy complementary distributed combined cooling, heating and power (CCHP) system is deeply studied. This system is applied on a commercial building in Beijing and it has complex configuration including natural gas energy source, renewable energy source and different energy conversion devices. Meanwhile, a separated cooling, heating and power (SCHP) supply system is also proposed. Their optimal operation strategies and performance are compared to show the advantages of multi-energy complementary system. Through simulation, the results show that the multi-energy complementary system operates with great performance and the optimal operation strategy is effective.

African swine fever (ASF) is a lethal contagious viral disease of domestic pigs and wild boars caused by the African swine fever virus (ASFV). The pandemic spread of ASF has had serious effects on the global pig industry. Virus genome sequencing and comparison play an important role in tracking the outbreaks of the disease and tracing the transmission of the virus. Although more than 140 ASFV genome sequences have been deposited in the public databases, the genome-wide diversity of ASFV remains unclear. Here we prepared a curated dataset of ASFV genome sequences by filtering genomes with sequencing errors as well as duplicated genomes. A total of 123 ASFV genome sequences were included in the dataset, representing 10 genotypes collected between 1949 and 2020. Phylogenetic analysis based on whole-genome sequences provided high-resolution topology in differentiating closely related ASFV isolates, and drew new clues in the classification of some ASFV isolates. Genome-wide diversity of ASFV genomes was explored by pairwise sequence similarity comparison and ORF distribution comparison. Tandem repeat sequences were found widely distributed and highly varied in ASFV genomes. Structural variation and highly variable poly G or poly C tracts also contributed to the genome diversity. This study expanded our knowledge on the patterns of genetic diversity and evolution of ASFV, and provided valuable information for diagnosis improvement and vaccine development.

Based on the semi-rigid characteristics of a double-cell prefabricated utility tunnel composed of groove-shaped elements (PUTCGE), this paper proposes an extended study of a stiffness reduction method for PUTCGEs by introducing the stiffness reduction and bending moment adjustment coefficients of the sidewalls. The effects of the joint stiffness ratio, the aspect ratio of width to height, the coefficient of subgrade reaction, and the embedment depth of the utility tunnel on the stiffness reduction and bending moment adjustment coefficients were investigated, and calculation formulas were established. The results showed that the stiffness reduction coefficient increased with the increase in the joint stiffness ratio, while the bending moment adjustment coefficient decreased with the increase in the joint stiffness ratio. The stiffness reduction coefficient increased with the decrease in the aspect ratio of width to height, while the effect of the aspect ratio of width to height on the bending moment adjustment coefficient was found to be very small. It was also found that neither the coefficient of subgrade reaction nor the embedment depth had a significant effect on the stiffness reduction and bending moment adjustment coefficients. The stiffness reduction method for the PUTCGE was validated through comparison with a full-scale physical model test. The proposed method can provide a reference for designing PUTCGEs for underground construction.

At the current stage, there is an urgent need for new techniques to dynamically calibrate advanced wide-range (up to 104 N~105 N) triaxial force transducers. Based on this background, this paper proposes a novel impact calibration method, specifically for the triaxial force transducer, with a wide range and high-frequency response. In this method, the Hopkinson bar, which is typically used to test the dynamic mechanical properties of materials, was used as a generator to generate reference input force for the transducer. In addition, unlike conventional methods, the transverse sensitivities of the transducer were given necessary importance in the proposed method. The calibration result of the triaxial force transducer was expressed in a sensitivity matrix, containing three main sensitivity coefficients and six transverse sensitivity coefficients. The least squares method (LSM) was used to fit the sensitivity matrix linearly. Calibration experiments were performed on a typical triaxial force transducer. Several key issues, involving the validity and the test range, of the method were further investigated numerically. The feasibility and validity of the method were eventually confirmed. The test range of the method can be up to 106 N.

Technology forecasting (TF) is an important way to address technological innovation in fast-changing market environments and enhance the competitiveness of organizations in dynamic and complex environments. However, few studies have investigated the complex process problem of how to select the most appropriate forecasts for organizational characteristics. This paper attempts to fill this research gap by reviewing the TF literature based on a complex systems perspective. We first identify four contexts (technology opportunity identification, technology assessment, technology trend and evolutionary analysis, and others) involved in the systems of TF to indicate the research boundary of the system. Secondly, the four types of agents (field of analysis, object of analysis, data source, and approach) are explored to reveal the basic elements of the systems. Finally, the visualization of the interaction between multiple agents in full context and specific contexts is realized in the form of a network. The interaction relationship network illustrates how the subjects coordinate and cooperate to realize the TF context. Accordingly, we illustrate suggest five trends for future research: (1) refinement of the context; (2) optimization and expansion of the analysis field; (3) extension of the analysis object; (4) convergence and diversification of the data source; and (5) combination and optimization of the approach.

Bulk metallic glasses (BMGs) have been extremely popular in recent decades, owing to their superior properties. However, how to improve the surface functions and durability of BMGs has always been a key engineering issue. In this work, a facile laser-based surface structuring technique was developed for modulation and control of the surface functionalities of Zr-based BMG. For this technique, a laser beam was first irradiated on the surface to create periodic surface structure, followed by heat treatment to control surface chemistry. Through experimental analyses, it was clearly shown that laser surface structuring turned the BMG surface superhydrophilic, and subsequent heat treatment turned the surface superhydrophobic. We confirmed that the combination of laser-induced periodic surface structure and modified surface chemistry contributed to the wettability transition. The laser-heat-treated surface also exhibited improved antifriction performance with the help of lubrication medium. This work provides a feasible method for surface modification of BMG, suggesting applications in the areas of medicine, biology and microelectronics.

The first complete chloroplast genome (cpDNA) sequence of Brachypodium sylvaticum was determined from Illumina HiSeq pair-end sequencing data in this study. The cpDNA is 136,392 bp in length, contains a large single-copy region (LSC) of 80,854 bp and a small single-copy region (SSC) of 12,765 bp, which were separated by a pair of inverted repeats (IR) regions of 21,383 bp. The genome contains 130 genes, including 84 protein-coding genes, 8 ribosomal RNA genes, and 38 transfer RNA genes. Further phylogenomic analysis showed that B. sylvaticum and B. distachyon clustered in a unique clade in Brachypodium genus.

To discuss the coagulation dysfunction in COVID-19 patients and to find new biomarkers to separate severe COVID-19 patients from mild ones. We use a retrospective analysis of 88 COVID-19 patients, and compare the coagulation function between severe and mild groups. We found the prothrombin time (PT), thrombin time (TT), D-dimer were significantly higher in the severe group ( P < 0.05), and the highest area under the curve (AUC) is 0.91 for D-dimer, while the AUC of PT and TT were 0.80 and 0.61 respectively. We identified that D-dimer has a better value in predicting patients who are likely to develop into severe cases, with the sensitivity and specificity were 84.4% and 88.8%, respectively. D-dimer may be a good biomarker to separate the severe COVID-19 patients from the mild ones.

Deafferentation pain (DP), a typical neuropathic pain, occurs due to peripheral or central sensory nerve injury, which causes abnormal discharge of the upstream neurons or C fibers. Current treatment methods for DP have multiple side effects. Bone marrow mesenchymal stem cells (BMSC) have been used to treat neuropathic pain because of their ability to regulate neuroinflammation. Glial cell-derived neurotrophic factor (GDNF) is a neurotrophic mediator that exerts neuroprotective effects in neurological diseases. In this study, we investigated whether DP could be alleviated by BMSCs and the underlying mechanism. In vitro study, microglia was stimulated by lipopolysaccharide and then co-cultured with BMSC, GDNF or siRNA GDNF-BMSC. In vivo study, BMSC or siRNA GDNF-BMSC was transplanted intramedullarily on the 21st day after DP surgery. The expression of inflammatory-related factors were detected by RT-PCR and ELISA, RT-PCR,flow cytometry and immunofluorescence staining were performed to detect the expression of microglial surface markers, and Western blot was used to detect the expression levels of p-NF-kb, pPI3K, and pAKT. The pain-related behavioral changes were detected 7 days after transplantation. ELISA and RT-PCR results showed that the production of inflammatory cytokines in lipopolysaccharide-stimulated microglia and DP model plasma was downregulated, while anti-inflammatory mediators were upregulated significantly following pretreatment with BMSCs or GDNF. Flow cytometry, immunofluorescence staining, and RT-PCR results showed that BMSCs inhibited the microglial M1 phenotype and promoted the M2 phenotype by secreting GDNF. Furthermore, modulation functions of BMSCs involve inhibiting NF-κB while promoting PI3K /AKT signaling pathway activation. We found that our in vivo DP model was completely deafferent and BMSC administration clearly alleviated symptoms of DP. This function was also, at least partly, achieved by GDNF. The present studies demonstrate that BMSC can inhibit neuroinflammation by transforming microglial destructive M1 phenotype into regenerative M2 phenotype, and thus alleviate DP,likely by suppressing the NF-κB signaling pathway while promoting the PI3K/AKT signaling pathway activation through producing GDNF. The present findings are in support of the potential therapeutic application of BMSCs and the pharmaceutical application of GDNF for DP.

Wetting behaviors of structured metal surfaces have received considerable attention due to the wide range of applications for commercial, industrial, and military uses as well as fundamental research interests. Due to its adaptability, precision, and ease of automation, laser-based texturing techniques are desirable platforms to create micro- and nano-structures, including laser-induced periodic surface structures, or hierarchical structures on a metal substrate. However, micro- and nanostructures alone often do not achieve the desired wettability. A subsequent surface chemistry modification method must be performed to attain target extreme wettability for laser textured metal substrates. This review aims to provide a systematic understanding of the interdependence of surface chemistry modification and physical surface structures formed during the laser-based surface engineering methods. The role of surface chemistry on top of the surface structures is presented to decide the final wetting scenario. Specifically, by controlling the surface chemistry of a laser textured surface, wetting can be modulated from extreme hydrophobicity to hydrophilicity, allowing freedom to achieve complex multi-wettability situations. In each section, we highlight the most fruitful approaches and underlying mechanisms to achieve a fitting combination of surface structures and surface chemistry. Durability and stability of the treated surface are also discussed in corrosive and abrasive environments. Finally, challenges in current studies and prospects in future research directions of this rapidly developing field are also discussed. This review will provide a comprehensive guideline for the design of laser texturing methods and the fabrication of extreme wetting surfaces for metal alloys.

African swine fever (ASF), caused by African swine fever virus (ASFV), is a devastating infectious disease of domestic pigs and wild boars, and has tremendous negative socioeconomic impact on the swine industry and food security worldwide. It is characterized as a notifiable disease by World Organisation for Animal Health (OIE). No effective vaccine or treatment against ASF has so far been available. Early detection and rapid diagnosis are of potential significance to control the spread of ASF. Recombinase-based isothermal amplification assay, recombinase polymerase amplification (RPA) developed by TwistDx (Cambridge, United Kingdom) or recombinase-aided amplification (RAA) by Qitian (Wuxi, China), is becoming a molecular tool for the rapid, specific, and cost-effective identification of multiple pathogens. In this study, we aim to investigate if RPA/RAA can be a potential candidate for on-site, rapid and primary detection of ASFV. A panel of 152 clinical samples previously well-characterized by OIE-recommended qPCR was enrolled in this study, including 20 weak positive (Ct value ≥ 30) samples. This panel was consisted of different types, such as EDTA-blood, spleen, lung, lymph node, kidney, tonsil, liver, brain. We evaluated two recombinase-based isothermal amplification assays, RPA or RAA, by targeting the ASFV B646L gene (p72), and validated the clinical performance in comparison with OIE real-time PCR. Our result showed that the analytical sensitivity of RPA and RAA was as 93.4 and 53.6 copies per reaction, respectively at 95% probability in 16 min, at 39°C. They were universally specific for all 24 genotypes of ASFV and no cross reaction to other pathogens including Classical swine fever virus (CSV), Foot-and-mouth disease virus (FMDV), Pseudorabies virus, Porcine circovirus 2 (PCV2), Porcine Reproductive and respiratory syndrome virus (PPRSV). The results on detection of various kinds of clinical samples indicated an excellent diagnostic agreement between RPA, RAA and OIE real-time PCR method, with the kappa value of 0.960 and 0.973, respectively. Compared to real-time PCR, the specificity of both RPA and RAA was 100% (94.40% ∼ 100%, 95% CI), while the sensitivity was 96.59% (90.36% ∼ 99.29%, 95% CI) and 97.73% (92.03% ∼ 99.72%, 95% CI), respectively. Our data demonstrate that the developed recombinase-based amplification assay (RPA/RAA), promisingly equipped with field-deployable instruments, offers a sensitive and specific platform for the rapid and reliable detection of ASFV, especially in the resource-limited settings for the purpose of screening and surveillance of ASF.

Efficiently learning representations of clinical concepts (i. e., symptoms, lab test, etc.) from unstructured clinical notes of electronic health record (EHR) data remain significant challenges, since each patient may have multiple visits at different times and each visit may contain different sequential concepts. Therefore, learning distributed representations from temporal patterns of clinical notes is an essential step for downstream applications on EHR data. However, existing methods for EHR representation learning can not adequately capture either contextual information per-visit or temporal information at multiple visits. In this study, we developed a new vector embedding method called EHR2Vec that can learn semantically-meaningful representations of clinical concepts. EHR2Vec incorporated the self-attention structure and showed its utility in accurately identifying relevant clinical concept entities considering time sequence information from multiple visits. Using EHR data from systemic lupus erythematosus (SLE) patients as a case study, we showed EHR2Vec outperforms in identifying interpretable representations compared to other well-known methods including Word2Vec and Med2Vec, according to clinical experts' evaluations.

Objective To evaluate clinical effects, and their correlations with preoperative computed tomography imaging parameters, in cases of lumbar spinal stenosis treated by endoscopic transforaminal decompression. Methods This retrospective study included orthopaedic patients who had undergone percutaneous endoscopic lumbar discectomy (PELD) for lumbar spinal stenosis. Clinical symptoms were evaluated by visual analogue scale (VAS), Oswestry Disability Index (ODI) and claudication distance. Overall clinical efficacy was evaluated by Macnab score. Results A total of 87 patients were included. Postoperative wound healing was good without complications. Macnab scores following PELD were ‘excellent’ in 41 cases (47.12%), ‘good’ in 30 cases (34.48%), ‘generally good’ in seven cases (8.04%), and ‘poor’ in nine cases (10.34%). The overall rate of optimal surgery was 81.60%. Postoperative pain (VAS) and ODI scores, and claudication distance, were significantly improved versus preoperative values. The soft tissue invasion ratio of the vertebral canal and invasion ratio of the nerve root canal were correlated with clinical efficacy. Conclusion Positive correlations were observed between clinical efficacy of endoscopic transforaminal decompression and preoperative vertebral canal soft tissue invasion ratio and nerve root canal invasion ratio in patients with lumbar spinal stenosis.

Insect Odorant-Binding Proteins (OBPs) play crucial roles in the discrimination, binding and transportation of odorants. Herein, the full-length cDNA sequence of Minus-C OBP1 (MaltOBP1) from the Japanese pine sawyer beetle, Monochamus alternatus, was cloned by 3′ and 5′ RACE-PCR and analyzed. The results showed that MaltOBP1 contains a 435 bp open reading frame (ORF) that encodes 144 amino acids, including a 21-amino acid signal peptide at the N-terminus. The matured MaltOBP1 protein possesses a predicted molecular weight of about 14 kDa and consists of six α-helices, creating an open binding pocket, and two disulfide bridges. Immunoblotting results showed that MaltOBP1 was most highly expressed in antennae in both sexes, followed by wings and legs. Fluorescence assays demonstrated that MaltOBP1 protein exhibited high binding affinity with (R)-(+)-α-pinene, (−)-β-pinene, trans-caryophyllene, (R)-(+)-limonene and (–)-verbenone, which are the main volatile compounds of the pine tree. Our combined results suggest that MaltOBP1 plays a role in host seeking behavior in M. alternatus.

Background. The aim of this study was to explore the role of hesperadin in intracerebral hemorrhage (ICH) mice, with the involvement of the mammalian ste20-like kinase 4 (MST4)/AKT signaling pathway. Methods. All mice were divided into four groups: sham group, sham+hesperidin group, ICH group, and ICH+hesperadin group. The effects of hesperadin were assessed on the basis of brain edema and neurobehavioral function. Furthermore, we observed MST4, AKT, phosphorylation of AKT (pAKT), and microtubule-associated protein light chain 3 (LC3) by western blotting. Protein localization of MST4 and LC3 was determined by immunofluorescence. Results. The expression of MST4 was upregulated at 12 h and 24 h after ICH. Brain edema was significantly decreased and neurological function was improved in the hesperadin treatment group compared to the ICH group (P

Open circuit failure mode in insulated-gate bipolar transistors (IGBT) is one of the most common faults in modular multilevel converters (MMCs). Several techniques for MMC fault diagnosis based on threshold parameters have been proposed, but very few studies have considered artificial intelligence (AI) techniques. Using thresholds has the difficulty of selecting suitable threshold values for different operating conditions. In addition, very little attention has been paid to the importance of developing fast and accurate techniques for the real-life application of open-circuit failures of IGBT fault diagnosis. To achieve high classification accuracy and reduced computation time, a fault diagnosis framework with a combination of the AC-side three-phase current, and the upper and lower bridges’ currents of the MMCs to automatically classify health conditions of MMCs is proposed. In this framework, the principal component analysis (PCA) is used for feature extraction. Then, two classification algorithms—multiclass support vector machine (SVM) based on error-correcting output codes (ECOC) and multinomial logistic regression (MLR)—are used for classification. The effectiveness of the proposed framework is validated by a two-terminal simulation model of the MMC-high-voltage direct current (HVDC) transmission power system using PSCAD/EMTDC software. The simulation results demonstrate that the proposed framework is highly effective in diagnosing the health conditions of MMCs compared to recently published results.

Abstract Background Insulin signaling pathway in β-cell is essential to promote β-cells proliferation and survival, while Nodal–ALK7–Smad3 signaling involves β-cells apoptosis. We attempted to address inter-relationship between Nodal and insulin in modulating β-cell proliferation and apoptosis. Methods Using INS-1 β-cells and isolated rat islets, we examined the effects of Nodal, insulin, or the two combined on β-cell proliferation and/or apoptosis. Results The β-cells under high-glucose or palmitate conditions showed significant up-regulation of Nodal expression and activation of its downstream signaling pathway resulted in increased cleaved caspase-3. Insulin treatment led to significantly attenuated Nodal-induced cell apoptotic pathway. Similar results were found in directly Nodal-treated β-cell that insulin could partially block Nodal-induced up-regulation of ALK7–Smad3–caspase-3 signaling pathways with significantly attenuated β-cell apoptosis. Interestingly, we found that insulin-induced Akt activation and downstream molecules including GSK-3β, β-catenin and ERK1/2 was significantly attenuated by the co-treatment with Nodal, resulted in decreased cell proliferation. Furthermore, Nodal decreased glucose-evoked calcium influx and played a negative role during glucose-stimulated insulin secretion in the β-cells. Immunocytochemistry studies showed that Nodal treatment translocated Smad3 from cytosol mostly to the nucleus; however, co-treatment with insulin significantly decreased Smad3 nuclear localization. Co-immunoprecipitation experiments showed a directly interaction between Smad3 and Akt, and this interaction was enhanced by co-treatment with insulin. Conclusions Our data suggest that the antagonistic interaction between Nodal and insulin has a role in the regulation of β-cell mass and secretion.

In view of the fact that vibration signals of rolling bearings are much contaminated by noise in the early failure period, this paper presents a new denoising SVD-VMD method by combining singular value decomposition (SVD) and variational mode decomposition (VMD). SVD is used to determine the structure of the underlying model, which is referred to as signal and noise subspaces, and VMD is used to decompose the original signal into several band-limited modes. Then the effective components are selected from these modes to reconstruct the denoised signal according to the difference spectrum (DS) of singular values and kurtosis values. Simulated signals and experimental signals of roller bearing faults have been analyzed using this proposed method and compared with SVD-DS. The results demonstrate that the proposed method can effectively retain the useful signals and denoise the bearing signals in extremely noisy backgrounds.

Bulk metallic glass (BMG) has received consistent attention from the research community owing to its superior physical and mechanical properties. Modulating and controlling the surface functionalities of BMG can be more interesting for the surface engineering community and will render more practical applications. In this work, a facile laser-based surface texturing technique is presented to modulate and control the surface functionalities (i.e., wettability and hardness) of Zr-based BMG. Laser surface texturing was first utilized to create periodic surface structures, and heat treatment was subsequently employed to control the surface chemistry. The experimental results indicate that the laser textured BMG surface became superhydrophilic immediately upon laser texturing, and it turned superhydrophobic after heat treatment. Through surface morphology and chemistry analyses, it was confirmed that the wettability transition could be ascribed to the combined effects of laser-induced periodic surface structure and controllable surface chemistry. In the meantime, the microhardness of the BMG surface has been remarkably increased as a result of laser surface texturing. The facile laser-based technique developed in this work has shown its effectiveness in modification and control of the surface functionalities for BMG, and it is expected to endow more useful applications.

The first complete chloroplast genome (cpDNA) sequence of Litsea cubeba was determined from Illumina HiSeq pair-end sequencing data in this study. The cpDNA is 152,725 bp in length, contains a large single-copy region (LSC) of 93,673 bp, and a small single-copy region (SSC) of 18,924 bp, which were separated by a pair of inverted repeats (IR) regions of 20,064 bp, each. The genome contains 126 genes, including 82 protein-coding genes, 8 ribosomal RNA genes, and 36 transfer RNA genes. The further phylogenomic analysis showed that L. cubeba and Litsea garrettii clustered in a clade in Lauraceae family.

The first complete chloroplast genome (cpDNA) sequence of Kadsura heteroclita was determined from Illumina HiSeq pair-end sequencing data in this study. The cpDNA is 153,289 bp in length, contains a large single copy region (LSC) of 85,774 bp and a small single copy region (SSC) of 18,201 bp, which were separated by a pair of inverted repeats (IR) regions of 24,657 bp. The genome contains 129 genes, including 84 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. Further phylogenomic analysis showed that K. heteroclita and K. interior clustered in a clade in Schisandraceae family.

The first complete chloroplast genome (cpDNA) sequence of Elaeocarpus braceanus was determined from Illumina HiSeq pair-end sequencing data in this study. The cpDNA is 158,225 bp in length, contains a large single-copy region (LSC) of 85,731 bp and a small single-copy region (SSC) of 17,654 bp, which were separated by a pair of inverted repeats (IR) regions of 27,420 bp. The genome contains 133 genes, including 88 protein-coding genes, 8 ribosomal RNA genes, and 37 transfer RNA genes. Further phylogenomic analysis showed that E. braceanus clustered in a clade in Celastrales order.

The first complete chloroplast genome (cpDNA) sequence of Taiwania flousiana was determined from Illumina HiSeq pair-end sequencing data in this study. The cpDNA is 132,565 bp in length, contains a large single copy region (LSC) of 72,930 bp and a small single copy region (SSC) of 59,477 bp, which were separated by a pair of inverted repeats (IR) regions of 79 bp. The genome contains 121 genes, including 83 protein-coding genes, 4 ribosomal RNA genes, and 34 transfer RNA genes. Further phylogenomic analysis showed that T. flousiana and Taiwania cryptomerioides clustered in a clade in Cupressaceae family.

On August 3, 2018, an outbreak of African swine fever in pigs was reported in China. We subjected a virus from an African swine fever–positive pig sample to phylogenetic analysis. This analysis showed that the causative strain belonged to the p72 genotype II and CD2v serogroup 8.

Dynamic microscale strain distributions with temporal resolution of 1 s in a smooth and a cracked Ti-6Al-4V alloys during one-cycle dwell fatigue tests are illustrated in videos (URL: https://drive.google.com/drive/folders/1pit_VV2apGOpETVfaJAAtL5Xl2CNOiJ3?usp=sharing). The tensile strain distributions were measured by the video sampling moiré method from the 1-μm-pitch grid images in a scanning electron microscope. The strain concentration factors of the smooth and the cracked specimens are 1.96 and 2.65, respectively. The plastic strain increment is 0.0007 during the displacement holding time of 591s in the smoothed specimen at maximum stress of 900 MPa., and 0.0008 during the displacement holding time of 593s in the cracked specimen at maximum stress of 870 MPa. The typical strain results are analyzed in 1-s-resolved strain mapping in Ti-6Al-4V alloys during dwell fatigue in SEM by video sampling moiré [1]. Keywords: Fatigue, Creep, Strain, Plastic deformation, Scanning electron microscope, Image processing

Immune checkpoint blockade (ICB) therapy has achieved remarkable clinical benefit in melanoma. However, our understanding of biomarkers that predict response to ICB remained obscure. Here we systematically analyzed the association between somatic mutations profile and clinicopathologic information from 336 melanoma patients treated by ICB (CTLA-4/PD-1). We identified eight new significantly mutated genes including COL5A1, SEMA3E, COL28A1, DGKG, RAPGEF5, GLDN, NCF2 and RCAN2. A mutational signature featured by enrichment of T > C mutations was identified to be associated with immune resistance (logistic regression model, OR, 2.59 [95%CI, 1.07 to 7.00], P = .043). High neoantigen quality was associated with prolonged immunotherapy survival (log-rank test, P = .009). This association remained significant after controlling for age, gender, stage and hypermutation (Cox proportional hazards model, HR, 0.56 [95%CI, 0.38 to 0.82], P = .003). Our findings shed new insights on biomarkers that are useful to predict melanoma patients who may benefit from ICB treatment; however, these biomarkers need to be validated in future studies.

Glucagon-like peptide-1 (GLP-1), an incretin hormone plays an important role in regulating glucose homeostasis. The therapeutic use of native GLP-1 is inadequate due to its short in vivo half-life. We recently developed a novel GLP-1 mimetics supaglutide, and demonstrated that this formulation retained native GLP-1 biological activities and possessed long-lasting GLP-1 actions. In this study, we further examined its abilities in regulating blood glucose in diabetic mice. We found that supaglutide stimulated insulin secretion in both mouse and human islets in a dose-dependent fashion. Oral glucose tolerance test conducted in normal ICR mice showed that supaglutide significantly decreased postprandial glucose excursions in a dose-dependent fashion. In type 2 diabetic db/db mice, a single-dose injection of supaglutide significantly decreased blood glucose levels, and this efficacy was lasted for at least 72 h in a dose-dependent fashion. During a 4-weeks intervention course supaglutide (twice injections per week) dose-dependently and significantly decreased fasting and random blood glucose levels in hyperglycemic db/db mice. Supaglutide, at a dose of 1.2 mg/kg, significantly reduced serum fructosamine levels. This was associated with significant enlargement of beta-cell mass, increased pancreatic insulin content, and increased plasma insulin level. Notably, during the intervention course supaglutide significantly reduced body-weight gain in these obese diabetic mice, associated with reduced fat mass (but not the lean mass), improved lipid profile, i.e., declined serum triglyceride, and free fatty acid levels compared to the placebo control. These finding reveals that supaglutide exerts beneficial effects in regulating blood glucose and lipid homeostasis in diabetic db/db mice.

Resveratrol, a bioactive compound in high quantities in Polygonum cuspidatum, has well-known health benefits. However, it mainly exists in its glycosidic form, polydatin, in plants. To increase the production of resveratrol for various uses in medicine, foods, and cosmetics, an efficient deglycosylation technique is needed for converting polydatin into resveratrol. We screened a new cellulolytic strain of Bacillus from herb compost, and we optimized parameters within the fermentation process using response surface methodology with a Box–Behnken design. The yield of cellulase reached 2701.08 U/L, corresponding to values that were 5.4 times as high as those under unoptimized conditions. The Bacillus cellulase possessed good thermostablity and was stable under both acidic and neutral conditions. The cellulase was then used in the pretreatment of P. cuspidatum root. After incubation at 50°C for 4 h with shaking at 150 rpm, the contents of piceid and resveratrol were determined to be 7.60 ± 0.15 and 9.72 ± 0.29 mg/g, respectively. To obtain complete deglycosylation, immobilized β-glucosidase (bgl2238) was added to the cellulase-treated extracts of P. cuspidatum root to convert residual polydatin into resveratrol. After the first cycle, the contents of piceid and resveratrol were determined to be 0 and 13.69 ± 0.30 mg/g, respectively. Moreover, enzyme activity showed little loss during up to 4 consecutive cycles. These results demonstrated that the immobilized β-glucosidase possessed high deglycosylation activity and outstanding operational stability. The mixture of Bacillus cellulase and immobilized bgl2238 appears promising as a means to increase the supply of resveratrol in the medicine market worldwide.

Objective This study was performed to identify a reasonable cutoff age for defining older patients with colorectal cancer (CRC) and to examine whether old age was related with increased colorectal cancer-specific death (CSD) and poor colorectal cancer-specific survival (CSS). Methods A total of 76,858 eligible patients from the surveillance, epidemiology, and end results (SEER) database were included in this study. The Cox proportional hazard regression model and the Chow test were used to determine a suitable cutoff age for defining the older group. Furthermore, a propensity score matching analysis was performed to adjust for heterogeneity between groups. A competing risk regression model was used to explore the impact of age on CSD and non-colorectal cancer-specific death (non-CSD). Kaplan–Meier survival curves were plotted to compare CSS between groups. Also, a Cox regression model was used to validate the results. External validation was performed on data from 1998 to 2003 retrieved from the SEER database. Results Based on a cutoff age of 70 years, the examined cohort of patients was classified into a younger group (n = 51,915,

Globally, human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in newborns, young children, and the elderly for which there is no vaccine. The RSV fusion (F) glycoprotein is a major target for vaccine development. Here, we describe a novel monoclonal antibody (designated as R4.C6) that recognizes both pre-fusion and post-fusion RSV F, and binds with nanomole affinity to a unique neutralizing site comprised of antigenic sites II and IV on the globular head. A 3.9 Å-resolution structure of RSV F-R4.C6 Fab complex was obtained by single particle cryo-electron microscopy and 3D reconstruction. The structure unraveled detailed interactions of R4.C6 with antigenic site II on one protomer and site IV on a neighboring protomer of post-fusion RSV F protein. These findings significantly further our understanding of the antigenic complexity of the F protein and provide new insights into RSV vaccine design.

PurposeAnal adenocarcinoma (AA) represents a rare condition, and little is known about the predictive factors of the outcomes or the optimal TNM staging system for curable AA. Using population-based data, we preliminarily sought to determine the prognostic factors and evaluate the existing T and N staging criteria of AA.MethodsWe analyzed the Surveillance, Epidemiology, and End Results 18 database to identify patients 20-80 years old who were diagnosed with AA or rectal adenocarcinoma (RA) and underwent abdominal perineal resection between 2004 and 2012. The difference between Kaplan-Meier survival curves was estimated by a log-rank test. A Cox proportional hazard regression model was used to adjust the effects of other covariates on survival in the propensity score-matched cohort, including age, gender, race, marital status, histology, grade of differentiation, tumor size, number of positive lymph nodes, radiotherapy, and chemotherapy.ResultsCompared to patients with RA, patients with AA had a worse CSS after controlling for other covariates (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.25-3.07; P0.05; >5 cm: HR, 1.01; 95% CI, 0.49-2.07; P>0.05) had no significant influence on survival. The number of positive lymph nodes (1-3: HR, 2.93; 95% CI, 1.55-5.53; PConclusionsAA confers a worse prognosis than RA does. The T staging criteria of anal carcinoma, dominated by tumor size, seem to be invalid for AA, while the number of positive lymph nodes is a prognostic factor.

Fault detection and classification are two of the challenging tasks in Modular Multilevel Converters in High Voltage Direct Current (MMC-HVDC) systems. To directly classify the raw sensor data without certain feature extraction and classifier design, a long short-term memory (LSTM) neural network is proposed and used for seven states of the MMC-HVDC transmission power system simulated by Power Systems Computer Aided Design/Electromagnetic Transients including DC (PSCAD/EMTDC). It is observed that the LSTM method can detect faults with 100% accuracy and classify different faults as well as provide promising fault classification performance. Compared with a bidirectional LSTM (BiLSTM), the LSTM can get similar classification accuracy, requiring less training time and testing time. Compared with Convolutional Neural Networks (CNN) and AutoEncoder-based deep neural networks (AE-based DNN), the LSTM method can get better classification accuracy around the middle of the testing data proportion, but it needs more training time.

Uncontrolled bleeding is the main cause of mortality from trauma. Collagen has been developed as an important hemostatic material due to its platelet affinity function. A bath sponge skeleton is rich in collagen, also known as spongin. To understand the hemostatic effect of spongin, spongin materials, SX, SFM and SR were prepared from the bath sponge Spongia officinalis, and hemostatic experiments were performed. The SX, SFM and SR were significantly better than the positive control, type I collagen, in shortening the whole blood clotting time in vitro and hemostasis upon rat tail amputation. In a hemostatic experiment of rabbit common carotid artery injury, the hemostatic time and 3 h survival rate of the SFM group were 3.00 ± 1.53 min and 100%, respectively, which are significantly better than those of the commercial hemostat CELOX-A (10.33 ± 1.37 min and 67%, respectively). Additionally, the SFM showed good coagulation effects in platelet-deficient blood and defibrinated blood, while also showing good biocompatibility. Through a variety of tests, we speculated that the hemostatic activity of the SFM is mainly caused by its hyperabsorbency, high affinity to platelets and high effective concentration. Overall, the SFM and spongin derivates could be potential hemostatic agents for uncontrolled bleeding and hemorrhagic diseases caused by deficiency or dysfunction of coagulation factors.

We first report a fabrication technique of nanoscale speckle patterns on polymers using broad ion beam milling. The proposed technique is simple and low-cost to produce speckles ranging from dozens of nanometers to less than three micrometers in a large area of several millimeters. Random patterns were successfully produced with an argon (Ar) ion beam on the surfaces of four kinds of polymers: the epoxy matrix of carbon fiber reinforced plastic, polyester, polyvinyl formal-acetal, and polyimide. The speckle morphologies slightly vary with different polymers. The fabricated speckle patterns have good time stability and are promising to be used to measure the nanoscale deformations of polymers using the digital image correlation method.

Twenty-three species of Ulota from South and Central America have previously been reported. A revision of the species suggests that number should be reduced to thirteen (Ulota billbuckii, Ulota fuegiana, Ulota germana, Ulota larrainii, Ulota luteola, Ulota macrocalycina, Ulota macrodontia, Ulota magellanica, Ulota phyllantha, Ulota pusilla, Ulota pycnophylla, Ulota rhytiore and Ulota streptodon) with eight names (Ulota aurantiaca = U. pycnophylla, Ulota carinata = U.fuegiana, Ulota fernandeziana = U. fuegiana, Ulota glabella = U. fuegiana, Ulota lativentrosa = U. pusilla, Ulota lobbiana = U. germana, Ulota pygmaeothecia = U. luteola and Ulota rufula = U. germana) reduced to synonyms, as well as three varieties (U. fuegiana var. crispata = U. fuegiana, U. rufula var. fagicola = U. germana and U. rufula var. patagonica = U. fuegiana). The taxonomic status of two names (Ulota angustissima and Ulota ventricosa) remains ambiguous. The typification of five names (U. macrodontia, U. magellanica, Ulota nothofagi, Ulota persubulata and U. pygmaeothecia) is proposed here. With the first report of Ulota crispa for South America, the total number of species accepted here for this region is fourteen. Two species (i.e. U. phyllantha and U. crispa) occur in both Hemispheres, one species (i.e. U. rhytiore) is only present in the Northern Hemisphere, whereas the remaining eleven species are all restricted to the Southern Hemisphere. Among them, nine (U. billbuckii, U. fuegiana, U. larrainii, U. macrocalycina, U. macrodontia, U. magellanica, U. pusilla, U. pycnophylla and U. streptodon) are restricted to South America, and two (U. germana and U. luteola) are distributed in South America and Oceania. The peristomes and spores of seven accepted species are illustrated in SEM micrographs. A key to all accepted species as well as descriptions, illustrations, synonyms, ecological and geographic distributions, and discussions are provided.

Objective: We studied the effects of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) on the proliferation of porcine theca interna (TI) cells and further elucidated the roles of IL-6 and TNF-α in the pathogenesis of polycystic ovary syndrome. Materials and Methods: TI cells were treated with 10 pg/mL, 100 pg/mL, and 1000 pg/mL IL-6 or TNF-α. TI cell proliferation was then examined by carboxyfluorescein diacetate succinimidyl ester labeling and flow cytometry. Results: Cell proliferation was not significantly different in TI cells cultured in medium alone (control) or in the presence of IL-6. At 72 hours of treatment, the mean fluorescence intensity was significantly lower in TI cells treated with 100 pg/mL and 1000 pg/mL TNF-α than in the control (p

In this paper, we explore learning methods to improve the performance of the open-circuit fault diagnosis of modular multilevel converters (MMCs). Two deep learning methods, namely, convolutional neural networks (CNN) and auto encoder based deep neural networks (AE-based DNN), as well as stand-alone SoftMax classifier are explored for the detection and classification of faults of MMC-based high voltage direct current converter (MMC-HVDC). Only AC-side three-phase current and the upper and lower bridges’ currents of the MMCs are used directly in our proposed approaches without any explicit feature extraction or feature subset selection. The two-terminal MMC-HVDC system is implemented in Power Systems Computer-Aided Design/Electromagnetic Transients including DC (PSCAD/EMTDC) to verify and compare our methods. The simulation results indicate CNN, AE-based DNN, and SoftMax classifier can detect and classify faults with high detection accuracy and classification accuracy. Compared with CNN and AE-based DNN, the SoftMax classifier performed better in detection and classification accuracy as well as testing speed. The detection accuracy of AE-based DNN is a little better than CNN, while CNN needs less training time than the AE-based DNN and SoftMax classifier.

Glucagon-like peptide 1 (GLP-1) improves insulin resistance of adipose tissue in obese humans. However, the mechanism of this effect is unclear. Perturbation of endoplasmic reticulum (ER) homeostasis impairs insulin signaling. We hypothesized that GLP-1 could directly improve insulin signaling in ER-stressed adipocytes. Here, we examined the effects of GLP-1 on ER stress response in fat cells in an obese and insulin-resistant murine model. We found that GLP-1 analog liraglutide reduced ER stress related gene expression in visceral fat cells accompanied by improved systemic insulin tolerance. Consistently, GLP-1 decreased CHOP expression and increased insulin stimulated AKT phosphorylation (p-AKT) in thapsigargin, a ER stress inducer, treated white fat cells differentiated from visceral stromal vascular fraction. We further found blocking CHOP expression increased insulin stimulated p-AKT in ER-stressed fat cells. Of note, we found mTOR signaling pathway contributed to the expression of ATF4 and subsequently the CHOP expression in ER stress response, while GLP-1 inhibited mTOR activity as exemplified by elevated autophagosome formation and increased LC3II/LC3I ratio. These findings suggest that GLP-1 directly modulates the ER stress response partially via inhibiting mTOR signaling pathway, leading to increased insulin sensitivity in adipocytes.

The measuring worm Erannis ankeraria belongs to the subfamily Ennominae of Geometridae. The mitogenome (GenBank accession number: MN046105) of E. ankeraria was sequenced, the new representative of the mitogenome of the subfamily. The nearly complete mitogenome is 15,250 bp totally, consisting of 13 protein-coding genes, two rRNAs, and 22 transfer RNAs. All genes have the similar locations and strands with that of other published species of Geometridae. The nucleotide composition biases towards A and T, which together made up 79.3% of the entirety. Bayesian inference analysis strongly supported the monophyly of Bombycoidea, Geometroidea, Noctuoidea, Papilionoidea, Pyraloidea, and Tortricoidea were strongly supported. This result also suggested that the Geometroidea was the sister to Bombycoidea, and then Noctuoidea was assigned to the sister group to the clade of Geometroidea + Bombycoidea, and then Pyraloidea was the sister group to the clade that contains Geometroidea, Bombycoidea, and Noctuoidea, and then Papilionoidea was the sister group to the clade that contains these four superfamilies mentioned above.

γ-aminobutyric acid (GABA) or glucagon-like peptide-1 based drugs, such as sitagliptin (a dipeptidyl peptidase-4 inhibitor), were shown to induce beta cell regenerative effects in various diabetic mouse models. We propose that their combined administration can bring forth an additive therapeutic effect. We tested this hypothesis in a multiple low-dose streptozotocin (STZ)-induced beta cell injury mouse model (MDSD). Male C57BL/6J mice were assigned randomly into four groups: non-treatment diabetic control, GABA, sitagliptin, or GABA plus sitagliptin. Oral drug administration was initiated 1 week before STZ injection and maintained for 6 weeks. GABA or sitagliptin administration decreased ambient blood glucose levels and improved the glucose excursion rate. This was associated with elevated plasma insulin and reduced plasma glucagon levels. Importantly, combined use of GABA and sitagliptin significantly enhanced these effects as compared with each of the monotherapies. An additive effect on reducing water consumption was also observed. Immunohistochemical analyses revealed that combined GABA and sitagliptin therapy was superior in increasing beta cell mass, associated with increased small-size islet numbers, Ki67+ and PDX-1+ beta cell counts; and reduced Tunel+ beta cell counts. Thus, beta cell proliferation was increased, whereas apoptosis was reduced. We also noticed a suppressive effect of GABA or sitagliptin on alpha cell mass, which was not significantly altered by combining the two agents. Although either GABA or sitagliptin administration delays the onset of MDSD, our study indicates that combined use of them produces superior therapeutic outcomes. This is likely due to an amelioration of beta cell proliferation and a decrease of beta cell apoptosis.

N-ethyl-N-nitrosourea (ENU) mutagenesis is a powerful tool to generate mutants on a large scale efficiently, and to discover genes with novel functions at the whole-genome level in Caenorhabditis elegans, flies, zebrafish and mice, but it has never been tried in large model animals. We describe a successful systematic three-generation ENU mutagenesis screening in pigs with the establishment of the Chinese Swine Mutagenesis Consortium. A total of 6,770 G1 and 6,800 G3 pigs were screened, 36 dominant and 91 recessive novel pig families with various phenotypes were established. The causative mutations in 10 mutant families were further mapped. As examples, the mutation of SOX10 (R109W) in pig causes inner ear malfunctions and mimics human Mondini dysplasia, and upregulated expression of FBXO32 is associated with congenital splay legs. This study demonstrates the feasibility of artificial random mutagenesis in pigs and opens an avenue for generating a reservoir of mutants for agricultural production and biomedical research.

GLP-1, an important incretin hormone plays an important role in the regulation of glucose homeostasis. However, the therapeutic use of native GLP-1 is limited due to its short half-life. We recently developed a novel GLP-1 mimetics (supaglutide) by genetically engineering recombinant fusion protein production techniques. We demonstrated that this formulation possessed long-lasting GLP-1 actions and was effective in glycemic control in both type 1 and type 2 diabetes rodent models. Here, we investigated the effects of supaglutide in regulating energy homeostasis in obese mice. Mice were fed with high-fat diet (HFD) for 6 months to induce obesity and then subjected to supaglutide treatment (300 μg/kg, bi-weekly for 4 weeks), and placebo as control. Metabolic conditions were monitored and energy expenditure was assessed by indirect calorimetry (CLAMS). Cold tolerance test was performed to evaluate brown-adipose tissue (BAT) activities in response to cold challenge. Glucose tolerance and insulin resistance were evaluated by intraperitoneal glucose tolerance test and insulin tolerance tests. Liver and adipose tissues were collected for histology analysis. Expression of uncoupling protein 1(Ucp1) in adipose tissues was evaluated by Western blotting. We found that supaglutide treatment reduced body weight, which was associated with reduced food intake. Compared to the placebo control, supaglutide treatment improved lipid profile, i.e., significantly decreased circulating total cholesterol levels, declined serum triglyceride, and free fatty acid levels. Importantly, the intervention significantly reduced fatty liver, decreased liver triglyceride content, and concomitantly ameliorated liver injury exemplified by declined hepatic alanine aminotransferase (ALT) and aspartic transaminase (AST) content. Remarkably, supaglutide reduced hepatic lipid accumulation and altered morphometry in favor of small adipocytes in fat. This is consistent with the observation that supaglutide increased tolerance of the mice to cold environment associated with up-regulation of Ucp1 in the inguinal fat. Furthermore, supaglutide improved glucose tolerance, and insulin sensitivity in the obese mice suggesting improved glucose and energy homeostasis. Our findings suggest that supaglutide exerts beneficial effect on established obesity through reducing energy intake and is associated with brown remodeling of white adipose tissue.

Background: We aimed to observe the effect of holistic nursing on patients undergoing hematodialysis for uremia who simultaneously were suffering from moderate to severe malnutrition. Methods: Eighty patients with uremia on maintenance hematodialysis with malnutrition between June 2014 and June 2015 from Yantaishan Hospital, Yantai, Shandong, China were included and equally and randomly were divided into the control group (n=43) and observation group (n=43). Routine nursing was used in the control group while holistic nursing was used in observation group (before, during and after dialysis) and the clinical effects in the two groups were compared after 3 months. Results: At follow-up visits, serum creatinine and urea nitrogen levels of the patients in the two groups were decreased, whereas hemoglobin and albumin levels were increased. In addition, these improvements were greater in the observation group and the differences were statistically significant (P

Spontaneous nucleation of actin is very inefficient in cells. To overcome this barrier, cells have evolved a set of actin filament nucleators to promote rapid nucleation and polymerization in response to specific stimuli. However, the molecular mechanism of actin nucleation remains poorly understood. This is hindered largely by the fact that actin nucleus, once formed, rapidly polymerizes into filament, thus making it impossible to capture stable multisubunit actin nucleus. Here, we report an effective double-mutant strategy to stabilize actin nucleus by preventing further polymerization. Employing this strategy, we solved the crystal structure of AMPPNP-actin in complex with the first two tandem W domains of Cordon-bleu (Cobl), a potent actin filament nucleator. Further sequence comparison and functional studies suggest that the nucleation mechanism of Cobl is probably shared by the p53 cofactor JMY, but not Spire. Moreover, the double-mutant strategy opens the way for atomic mechanistic study of actin nucleation and polymerization.

In this study, we investigated interactions among microglia (MG), bone marrow mesenchymal stem cells (BMSCs) and neurons in cerebral ischemia and the potential mechanisms using an in vitro oxygen-glucose deprivation (OGD) model. Rat BMSCs were incubated with conditioned medium (CM) from in vitro cultures of OGD-activated rat MG and murine BV2 MG cells. Effects of glial cell-derived neurotrophic factor (GDNF) on rat neuron viability, apoptosis, lactate dehydrogenase (LDH) leakage and mitochondrial membrane potential (MMP) were analyzed in this model. OGD-activated MG promoted GDNF production by BMSCs (P < 0.01). TNFα, but not IL6 or IL1β, promoted GDNF production by BMSCs (P < 0.001). GDNF or CM pre-treated BMSCs elevated neuronal viability and suppressed apoptosis (P < 0.05 or P < 0.01); these effects were inhibited by the RET antibody. GDNF activated MEK/ERK and PI3K/AKT signaling but not JNK/c-JUN. Furthermore, GDNF upregulated B cell lymphoma 2 (BCL2) and heat shock 60 kDa protein 1 (HSP60) levels, suppressed LDH leakage, and promoted MMP. Thus, activated MG produce TNFα to stimulate GDNF production by BMSCs, which prevents and repairs OGD-induced neuronal injury, possibly via regulating MEK/ERK and PI3K/AKT signaling. These findings will facilitate the prevention and treatment of neuronal injury by cerebral ischemia.

Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery.

Glucagon-like peptide-1 (GLP-1) plays a role in the regulation of adipogenesis; however, the precise underlying molecular mechanism has not been fully defined. Wnt was recently identified as an important regulator of adipogenesis. This study aimed to investigate the involvement of the Wnt signaling pathway in the effects of GLP-1 on adipocyte differentiation. 3T3-L1 cells were induced to differentiate. The changes in the expression levels of adipogenic transcription factors and Wnts and the phosphorylation level and subcellular localization of β-catenin were quantified after GLP-1 treatment. GLP-1 stimulated adipocyte differentiation and lipid accumulation, which were accompanied by the expression of adipocyte marker genes. The expression of Wnt4 was upregulated in the process of adipocyte differentiation, which was further enhanced by treatment with GLP-1. β-catenin, an important mediator of the Wnt pathway, was immediately dephosphorylated and translocated from cytoplasm to nucleus when differentiation was induced. In the presence of GLP-1, however, β-catenin was redirected to the cell plasma membrane leading to its decreased accumulation in the nucleus. Knockdown of Wnt4 blocked the effect of GLP-1 on the cellular localization of β-catenin and expression level of adipogenic transcription factors. Our findings showed that GLP-1 promoted adipogenesis through the modulation of the Wnt4/β-catenin signaling pathway, suggesting that the GLP-1-Wntβ-catenin system might be a new target for the treatment of metabolic disease.