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The incubation behavior of geese seriously affects their egg production performance. Studies on incubation behavior have identified functional genes, but the regulatory architecture relationship between functional genes and chromatin accessibility remains poorly understood. Here, we present an integrated analysis of open chromatin profiles and transcriptome to identify the cis-regulatory element and their potential transcription factors involved in regulating incubation behavior in goose pituitary. Assay for transposase-accessible chromatin sequencing (ATAC-seq) revealed that open chromatin regions increased in the pituitary during the transition from incubation behavior to laying. We identified 920 significant differential accessible regions (DARs) in the pituitary. Compared to the laying stage, most DARs had higher chromatin accessibility in the brooding stage. Motif analysis of open DARs showed that the most significant transcription factor (TF) occupied sites predominantly enriched in motifs binding to the RFX family (RFX5, RFX2, and RFX1). While the majority of TF motifs enriched under sites of the nuclear receptor (NR) family (ARE, GRE, and PGR) in closed DARs at the incubation behavior stage. Footprint analysis indicated that the transcription factor RFX family exhibited higher binding on chromatin at the brooding stage. To further elucidate the effect of changes in chromatin accessibility on gene expression levels, a comparison of the transcriptome revealed 279 differentially expressed genes (DEGs). The transcriptome changes were associated with processes of steroid biosynthesis. By integrating ATAC-seq and RNA-seq, few DARs directly affect incubation behavior by regulating the transcription levels of genes. Five DAR-related DEGs were found to be closely related to maintaining the incubation behavior in geese. Footprinting analysis revealed a set of transcription factors (RFX1, RFX2, RFX3, RFX5, BHLHA15, SIX1, and DUX) which displayed the highest activity at the brooding stage. SREBF2 was predicted to be the unique differentially expressed transcription factor whose mRNA level was down-regulated and enriched in hyper-accessible regions of PRL in the broody stage. In the present study, we comprehensively profiled the transcriptome and chromatin accessibility in the pituitary related to incubation behavior. Our findings provided insight into the identification and analysis of regulatory elements in goose incubation behavior. The epigenetic alterations profiled here can help decipher the epigenetic mechanisms that contribute to the regulation of incubation behavior in birds.

Background: Carotid web (CaW) is a rare disease, but it is associated with cryptogenic recurrent ischemic stroke. Due to a lack of epidemiological data and a generally low awareness of the disease, CaW is difficult to diagnose and is even prone to misdiagnosis. It is often treated with medical management, carotid endarterectomy (CEA) and stent implantation. These therapies are aimed at preventing cerebrovascular events. Case presentation: We describe the case of a young adult patient who suffered ischemic stroke for unknown reasons. He was successfully treated with CEA and finally diagnosed with CaW. Recommendation: People should improve their knowledge of CaW. The correct diagnosis of CaW is important for its therapeutic strategies. Medical management alone may not effectively prevent recurrent stroke for patients with CaW. CEA is an ideal option to treat CaW for lesion removal, obtaining the pathologic results and engaging in satisfactory short-term follow-up.

Both hypothalamic neurotransmitters and serum steroid hormones are impacted by photoperiod and have effects on physiology and seasonal reproductive. However, the relationship between circulating gonadal steroids and hypothalamic neurotransmitters underlying different photoperiod is still unclear. To further understand the crosstalk of neurotransmitters and steroids in seasonal reproduction, metabolic changes of 27 neurotransmitters concentrated in hypothalamus tissues and 42 steroids hormones in serum were assessed during two artificial photoperiodic programs. The results showed that photoperiod induce testicular atrophy and recrudescence. In L-to-S groups, significantly decreased levels of testosterone concentration were found in serum (P < 0.001) and increased 11-Dehydrocorticosterone (P < 0.05); Testosterone were almost undetectable at SD_14d. In addition, the hypothalamus exhibited significantly increased arginine and 4-aminobutyric acid (GABA) concentration and decreased serotonin and epinephrine content (P < 0.01 or P < 0.05). Accordingly, serum testosterone and androstenedione became detectable at LD_3d in the S-to-L group and were markedly increase at LD_7d. Furthermore, Serum androstenedione showed a significant increase with long light expose (P < 0.01). Additionally, the hypothalamus exhibited both significantly increased L.Tryptophan and phenylalanine concentration, as well as decreased L-glutamine and L-glutamine.acid content (P < 0.01 or P < 0.05). Serotonin metabolism showed significant differences between L-to-S group and S-to-L group. Furthermore, in the correlation analysis, serum testosterone had a positive correlation with 5-Hydroxyindole-3-acetic acid (5-HIAA), while Androstenedione was significantly negative with L.Tryptophan in L-to-S (P < 0.05). However, in S-to-L group, serum testosterone showed strong negative correlation with both serotonin and 5-HIAA (P < 0.05), but positive correlation with L.Tryptophan (P < 0.01), while Androstenedione was significantly negative correlation with both serotonin (P < 0.05) and L-Glutamine (P < 0.01). Photoperiod also had significant effects on the mRNA expression. We found significant differences in gene expression patterns of both serotonin signaling and steroid biosynthesis, while MAOB, NR5A1, and 3β-HSD showed an opposite tendency between two groups. Taken together, our results revealed that circulating gonadal steroids and hypothalamic neurotransmitters were significantly impact quail’s seasonal reproduction. Circulating gonadal steroids have different effects on neurotransmitter at different photoperiodism, which may coordinately influence the seasonal reproduction of quails.

Abstract Background The zero-profile anchored cage (ZP) has been widely used for its lower occurrence of dysphagia. However, it is still controversial whether it has the same stability as the cage-plate construct (CP) and increases the incidence of postoperative subsidence. We compared the rate of subsidence after anterior cervical discectomy and fusion (ACDF) with ZP and CP to determine whether the zero-profile device had a higher subsidence rate. Methods We performed a meta-analysis of studies that compared the subsidence rates of ZP and CP. An extensive and systematic search covered the PubMed and Embase databases according to the PRISMA guidelines and identified ten articles that satisfied our inclusion criteria. Relevant clinical and radiological data were extracted and analyzed by the RevMan 5.3 software. Results Ten trials involving 626 patients were included in this meta-analysis. The incidence of postoperative subsidence in the ZP group was significantly higher than that in the CP group [15.1% (89/588) versus 8.8% (51/581), OR = 1.97 (1.34, 2.89), P = 0.0005]. In the subgroup analysis, we found that the definition of subsidence did not affect the higher subsidence rate in the ZP group. Considering the quantity of operative segments, there was no significant difference in the incidence of subsidence between the two groups after single-level fusion (OR 1.43, 95% CI 0.61–3.37, P = 0.41). However, the subsidence rate of the ZP group was significantly higher than that of the CP group (OR 2.61, 95% CI 1.55–4.40, P = 0.0003) after multilevel (≥ 2-level) procedures. There were no significant differences in intraoperative blood loss, JOA score, NDI score, fusion rate, or cervical alignment in the final follow-up between the two groups. In addition, the CP group had a longer operation time and a higher incidence of dysphagia than the ZP group at each follow-up time. Conclusion Based on the limited evidence, we suggest that ZP has a higher risk of postoperative subsidence than CP, although with elevated swallowing discomfort. A high-quality, multicenter randomized controlled trial is required to validate our results in the future.

Drug repurposing is an efficient strategy for new drug discovery. Our latest study found that nitazoxanide (NTZ), an approved anti-parasite drug, was an autophagy activator and could alleviate the symptom of Alzheimer's disease (AD). In order to further improve the efficacy and discover new chemical entities, a series of NTZ-based derivatives were designed, synthesized, and evaluated as autophagy activator against AD. All compounds were screened by the inhibition of phosphorylation of p70S6K, which was the direct substrate of mammalian target of rapamycin (mTOR) and its phosphorylation level could reflect the mTOR-dependent autophagy level. Among these analogs, compound 22 exhibited excellent potency in promoting β-amyloid (Aβ) clearance, inhibiting tau phosphorylation, as well as stimulating autophagy both in vitro and in vivo. What's more, 22 could effectively improve the memory and cognitive impairments in APP/PS1 transgenic AD model mice. These results demonstrated that 22 was a potential candidate for the treatment of AD. Key words: Alzheimer's disease, Autophagy, Nitazoxanide, β-amyloid, Tau protein

Due to the characteristics of the spectrum integration, information redundancy, spectrum mixing phenomenon and nonlinearity of the hyperspectral remote sensing images, it is a major challenging task to classify the hyperspectral remote sensing images. Therefore, a hyperspectral remote sensing image classification method, named QGASR-CNN is proposed in this paper. In the QGASR-CNN, a quantum genetic-optimized sparse representation method is designed to obtain the over-complete dictionary with sparsity, and achieve the feature sparse representation to construct the sparse feature matrix of hyperspectral remote sensing image pixel groups. Then the convolution neural network(CNN) directly convolutes with image pixels to build the feature mapping relation by using convolution operation. Finally, in order to testify the effectiveness of the QGASR-CNN, the actual hyperspectral remote sensing image datasets are selected in here. The comparison results show that the QGASR-CNN sparsely represents the features of hyperspectral remote sensing images and improves the classification accuracy. It can effectively alleviate the problems of the small samples and `salt and pepper misclassification'.

Aluminum alloys have low weldability by conventional fusion welding processes. Friction stir welding (FSW) is a promising alternative to traditional fusion welding techniques for producing high quality aluminum joints. The quality of the welded joints is highly dependent on the process parameters used during welding. In this research, a new approach was developed to predict the process parameters and mechanical properties of AA6061-T6 aluminium alloy joints in terms of ultimate tensile strength (UTS). A new hybrid artificial neural network (ANN) approach has been proposed in which Henry Gas Solubility Optimization (HGSO) algorithm has been incorporated to improve the performance of Random Vector Functional Link (RVFL) network. The HGSO-RVFL model was constructed with four parameters; rotational speed, welding speed, tilt angle, and pin profile. The validity of the model was tested, and it was demonstrated that the HGSO-RVFL model is a powerful technique for predicting the UTS of friction stir welded (FSWD) joints. In addition, the effects of process parameters on UTS of welded joints were discussed, where a significant agreement was observed between experimental results and predicted results which indicates the high performance of the model developed to predict the appropriate welding parameters that achieve optimal UTS.

Land cover semantic segmentation is an important technique in land. It is very practical in land resource protection planning, geographical classification, surveying and mapping analysis. Deep learning shows excellent performance in picture segmentation in recent years, but there are few semantic segmentation algorithms for land cover. When dealing with land cover segmentation tasks, traditional semantic segmentation networks often have disadvantages such as low segmentation precision and weak generalization due to the loss of image detail information and the limitation of weight distribution. In order to achieve high-precision land cover segmentation, this article develops a multi-scale feature aggregation network. Traditional convolutional neural network downsampling procedure has problems of detail information loss and resolution degradation; to fix these problems, a multi-scale feature extraction spatial pyramid module is made to assemble regional context data from different areas. In order to address the issue of incomplete information of traditional convolutional neural networks at multiple sizes, a multi-scale feature fusion module is developed to fuse attributes from various layers and several sizes to boost segmentation accuracy. Finally, a multi-scale convolutional attention module is presented to enhance the segmentation’s attention to the target in order to address the issue that the classic convolutional neural network has low attention capacity to the building waters in land cover segmentation. Through the contrast experiment and generalization experiment, it can be clearly demonstrated that the segmentation algorithm proposed in this paper realizes the high precision segmentation of land cover.

The present study aimed to explore the mechanism by which PAMK alleviates cyclophosphamide (CTX)-induced ferroptosis in thymocytes. One-day-old goslings were divided into four groups (10 goslings/group). The CON and CTX groups were fed a basic diet. The PAMK and CTX + PAMK groups were fed the basic diet mixed with PAMK (400 mg/kg). Moreover, the CTX and CTX + PAMK groups were given a daily injection of 40 mg/kg BW of CTX (at 19, 20, and 21 days of age). On the other hand, the CON and PAMK groups were given 0.5 mL of sterilized saline into the leg muscle (at 19, 20, and 21 days of age). The goslings were fed for 28 days. The ferroptosis pathway was enriched in transcriptome sequencing. Compared to the CON group, the thymus in the CTX group underwent injury, and the mitochondria of thymocytes showed features of ferroptosis. PAMK treatment alleviated ferroptosis in thymocytes and thymus injury, and CTX-induced elevated levels of oxidative stress and iron content restored GPX4 protein expression (p < 0.05) and inhibited the CTX-induced activation of the ferroptosis pathway (p < 0.05). Conclusively, PAMK could reduce thymus injury by alleviating CTX-induced thymocyte ferroptosis in gosling to alleviate the immunosuppression caused by CTX in the organism.

ABSTRACT: Polysaccharide Of Atractylodes Macrocephala Koidz (PAMK) has been proved to have anti-cancer, antitumor, anti-inflammation function and improve the immune level of the organism. The miRNA plays a very important role in regulating the immune function by negatively regulate the expression of target genes. To explore the molecular mechanism of PAMK active the lymphocytes, thirty 61-d-old geese were randomly divided into 4 groups (C, CTX, PAMK, PAMK+CTX). The thymus morphology, the level of serum granulocyte-macrophage colony-stimulating factor (GMC-SF), IL-1β, IL-3, IL-5, the relative mRNA expression of CD25, novel_mir2, CTLA4 and CD28 signal pathway were measured. Further more, the lymphocytes was extracted from thymus to measure the relative mRNA expression of CD28 signal pathway. The results showed that PAMK could significantly maintain normal cell morphology of thymus, alleviate the decrease level of GMC-SF, IL-1β, IL-5, IL-6, TGF-β, the increase level of IL-4, IL-10, and the decrease relative mRNA expression of novel_mir2, CD25 and CD28 signal pathway in thymus and lymphocytes induced by cyclophosphamide (CTX). In conclusion, PAMK alleviated the decreased T lymphocytes activation levels induced by CTX through novel_mir2/CTLA4/CD28/AP-1 signal pathway.

Graph neural networks (GNNs) with feature propagation have demonstrated their power in handling unstructured data. However, feature propagation is also a smooth process that tends to make all node representations similar as the number of propagation increases. To address this problem, we propose a novel Block-Based Adaptive Decoupling (BBAD) Framework to produce effective deep GNNs by utilizing backbone networks. In this framework, each block contains a shallow GNN with feature propagation and transformation decoupled. We also introduce layer regularizations and flexible receptive fields to automatically adjust the propagation depth and to provide different aggregation hops for each node, respectively. We prove that the traditional coupled GNNs are more likely to suffer from over-smoothing when they become deep. We also demonstrate the diversity of outputs from different blocks of our framework. In the experiments, we conduct semi-supervised and fully supervised node classifications on benchmark datasets, and the results verify that our method can not only improve the performance of various backbone networks, but also is superior to existing deep graph neural networks with less parameters.

Background: Hepatic stellate cell (HSC) activation induced by transforming growth factor β1 (TGF-β1) plays a pivotal role in fibrogenesis, while the complex downstream mediators of TGF-β1 in such process are largely unknown. Methods: We performed pharmacoproteomic profiling of the mice liver tissues from control, carbon tetrachloride (CCl4)-induced fibrosis and NPLC0393 administrated groups. The target gene MAT2A was overexpressed or knocked down in vivo by tail vein injection of AAV vectors. We examined NF-κB transcriptional activity on MAT2A promoter via luciferase assay. Intracellular SAM contents were analyzed by LC-MS method. Findings: We found that methionine adenosyltransferase 2A (MAT2A) is significantly upregulated in the CCl4-induced fibrosis mice, and application of NPLC0393, a known small molecule inhibitor of TGF-β1 signaling pathway, inhibits the upregulation of MAT2A. Mechanistically, TGF-β1 induces phosphorylation of p65, i.e., activation of NF-κB, thereby promoting mRNA transcription and protein expression of MAT2A and reduces S-adenosylmethionine (SAM) concentration in HSCs. Consistently, in vivo and in vitro knockdown of MAT2A alleviates CCl4- and TGF-β1-induced HSC activation, whereas in vivo overexpression of MAT2A facilitates hepatic fibrosis and abolishes therapeutic effect of NPLC0393. Interpretation: This study identifies TGF-β1/p65/MAT2A pathway that is involved in the regulation of intracellular SAM concentration and liver fibrogenesis, suggesting that this pathway is a potential therapeutic target for hepatic fibrosis. Fund: This work was supported by National Natural Science Foundation of China (No. 81500469, 81573873, 81774196 and 31800693), Zhejiang Provincial Natural Science Foundation of China (No. Y15H030004), the National Key Research and Development Program from the Ministry of Science and Technology of China (No. 2017YFC1700200) and the Key Program of National Natural Science Foundation of China (No. 8153000502).

In this paper, the deviation from eutectic composition in boundary layer for eutectic growth is studied by phase-field method. According to a series of artificial phase diagram, the lamellar eutectic growth of these alloy is simulated during directional solidification. At steady state, average growth velocity of eutectic lamella is equal to the pulling velocity. With the increasing of the liquidus slope of β phase, the average composition in boundary layer would deviate from eutectic composition and the deviation increases. The constitutional undercooling difference between both solid phases caused by the deviation increases with the increasing of the deviation. The β phase would develop a depression under the influence of the deviation.

Dropout is an effective regularization method for deep learning tasks. Several variants of dropout based on sampling with different distributions have been proposed individually and have shown good generalization performance on various learning tasks. Among these variants, the canonical Bernoulli dropout is a discrete method, while the uniform dropout and the Gaussian dropout are continuous dropout methods. When facing a new learning task, one must make a decision on which method is more suitable, which is somehow unnatural and inconvenient. In this paper, we attempt to change the selection problem to a parameter tuning problem by proposing a general form of dropout, β-dropout, to unify the discrete dropout with continuous dropout. We show that by adjusting the shape parameter β, the β-dropout can yield the Bernoulli dropout, uniform dropout, and approximate Gaussian dropout. Furthermore, it can obtain continuous regularization strength, which paves the way for self-adaptive dropout regularization. As a first attempt, we propose a self-adaptive β-dropout, in which the parameter β is tuned automatically following a pre-designed strategy. The β-dropout is tested extensively on the MNIST, CIFAR-10, SVHN, NORB, and ILSVRC-12 datasets to investigate its superior performance. The results show that the β-dropout can conduct finer control of its regularization strength, therefore obtaining better performance.

Objective This meta-analysis investigated the analgesic effects of erector spinae plane block (ESPB) in patients undergoing breast surgery. Methods PubMed, Embase, Web of Science, and the Cochrane Library were searched from database establishment to January 31, 2020. Two reviewers independently extracted the data. The primary outcomes were pain scores and opioid consumption during the first 24 hours after surgery. The risk of bias of the included studies was assessed according to the Cochrane Handbook. Results Six randomized controlled trials of 415 patients were included. Compared with the control value, the pain score was significantly lower in the ESPB group at different time points postoperatively. Patients who underwent ESPB required lower opioid consumption (standardized mean difference = −2.02, 95% confidence interval [CI] = −2.85 to −1.20, I 2 = 91%. The rates of postoperative nausea (risk ratio [RR] = 0.79, 95% CI = 0.48–1.30, I 2 = 47%) and postoperative vomiting (RR = 0.76, 95% CI = 0.30–1.96, I 2 = 33%) did not differ between the groups. The quality of evidence was low or very low. Conclusions ESPB significantly alleviated pain and reduced opioid consumption after breast surgery. Further research is needed to expand its clinical application. PROSPERO registration number CRD42020167900

Background. Nowadays, acute intracerebral hemorrhage stroke (AICH) still causes higher mortality. Liangxue Tongyu Formula (LXTYF), originating from a traditional Chinese medicine (TCM) prescription, is widely used as auxiliary treatment for AICH. Objective. To dig into the multicomponent, multitarget, and multipathway mechanism of LXTYF on treating AICH via network pharmacology and RNA-seq. Methods. Network pharmacology analysis was used by ingredient collection, target exploration and prediction, network construction, and Gene Ontology (GO) and KEGG analysis, with the Cytoscape software and ClusterProfiler package in R. The RNA-seq data of the AICH-rats were analyzed for differential expression and functional enrichments. Herb-Compound-Target-Pathway (H-C-T-P) network was shown to clarify the mechanism of LXTYF for AICH. Results. 76 active ingredients (quercetin, Alanine, kaempferol, etc.) of LXTYF and 376 putative targets to alleviate AICH (PTGS2, PTGS1, ESR1, etc.) were successfully identified. The protein-protein interaction (PPI) network indicated the important role of STAT3. The functional enrichment of GO and KEGG pathway showed that LXTYF is most likely to influence MAPK and PI3K-Akt signaling pathways for AICH treatment. From the RNA-seq of AICH-rats, 583 differential mRNAs were identified and 14 of them were consistent with the putative targets of LXTYF for AICH treatment. The KEGG pathway enrichment also implied that the MAPK signaling pathway was the most correlated one among all the related signaling pathways. Many important targets with expression changes of LXTYF for AICH treatment and their related pathways are great markers of antioxidation, anti-inflammatory, antiapoptosis, and lowering blood pressure, which indicated that LXTYF may play mutiroles in the mechanisms for AICH treatment. Conclusion. The LXTYF attenuates AICH partially by antioxidation, anti-inflammatory, and antiapoptosis and lowers blood pressure roles through regulating the targets involved MAPK, calcium, apoptosis, and TNF signaling pathway, which provide notable clues for further experimental validation.

Background: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes severely afflicting the patients, while there is yet no effective medication against this disease. As Kv2.1 channel functions potently in regulating neurological disorders, the present work was to investigate the regulation of Kv2.1 channel against DPN-like pathology of DPN model mice by using selective Kv2.1 inhibitor SP6616 (ethyl 5-(3-ethoxy-4-methoxyphenyl)-2-(4-hydroxy-3-methoxybenzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate) as a probe. Methods: STZ-induced type 1 diabetic mice with DPN (STZ mice) were defined at 12 weeks of age (4 weeks after STZ injection) through behavioral tests, and db/db (BKS Cg-m+/+Leprdb/J) type 2 diabetic mice with DPN (db/db mice) were at 18 weeks of age. SP6616 was administered daily via intraperitoneal injection for 4 weeks. The mechanisms underlying the amelioration of SP6616 on DPN-like pathology were investigated by RT-PCR, western blot and immunohistochemistry technical approaches against diabetic mice, and verified against the STZ mice with Kv2.1 knockdown in dorsal root ganglion (DRG) tissue by injection of adeno associated virus AAV9-Kv2.1-RNAi. Amelioration of SP6616 on the pathological behaviors of diabetic mice was assessed against tactile allodynia, thermal sensitivity and motor nerve conduction velocity (MNCV). Findings: SP6616 treatment effectively ameliorated the threshold of mechanical stimuli, thermal sensitivity and MNCV of diabetic mice. Mechanism research results indicated that SP6616 suppressed Kv2.1 expression, increased the number of intraepidermal nerve fibers (IENFs), improved peripheral nerve structure and vascular function in DRG tissue. In addition, SP6616 improved mitochondrial dysfunction through Kv2.1/CaMKKβ/AMPK/PGC-1α pathway, repressed inflammatory response by inhibiting Kv2.1/NF-κB signaling and alleviated apoptosis of DRG neuron through Kv2.1-mediated regulation of Bcl-2 family proteins and Caspase-3 in diabetic mice. Interpretation: Our work has highly supported the beneficial of Kv2.1 inhibition in ameliorating DPN-like pathology and highlighted the potential of SP6616 in the treatment of DPN. Funding: Please see funding sources.

Summary: Diabetic peripheral neuropathy (DPN) is a common diabetic complication and has yet no efficient medication. Here, we report that antispasmodic drug drofenine (Dfe) blocks Kv2.1 and ameliorates DPN-like pathology in diabetic mice. The underlying mechanisms are investigated against the DPN mice with in vivo Kv2.1 knockdown through adeno associated virus AAV9-Kv2.1-RNAi. Streptozotocin (STZ) induced type 1 or db/db type 2 diabetic mice with DPN exhibited a high level of Kv2.1 protein in dorsal root ganglion (DRG) tissue and a suppressed neurite outgrowth in DRG neuron. Dfe promoted neurite outgrowth by inhibiting Kv2.1 channel and/or Kv2.1 mRNA and protein expression level. Moreover, it suppressed inflammation by repressing IκBα/NF-κB signaling, inhibited apoptosis by regulating Kv2.1-mediated Bcl-2 family proteins and Caspase-3 and ameliorated mitochondrial dysfunction through Kv2.1/CaMKKβ/AMPK/PGC1α pathway. Our work supports that Kv2.1 inhibition is a promisingly therapeutic strategy for DPN and highlights the potential of Dfe in treating this disease.

Background: This study aimed to evaluate real-time polymerase chain reaction coupled with multiplex probe melting curve analysis (PCR-MCA) for pathogen detection in patients with suspected bloodstream infections (BSIs).Methods: A PCR-MCA assay was developed for simultaneous identification of 28 kinds of the most common pathogens and two resistance genes within a few hours. The diagnostic performance of the PCR-MCA assay was determined and compared to the results of blood culture.Results: A total of 2,844 consecutive new episodes of suspected BSIs in 2,763 patients were included in this study. There were 269 episodes of pathogens identified by blood culture. For all the pathogens tested, the PCR-MCA assay exhibited a sensitivity of 88.8% (239/269), specificity of 100% (2,575/2,575), and agreement of 98.9% (2,814/2,844). For the pathogens on the PCR-MCA list, the PCR-MCA results had a sensitivity of 99.2% (239/241), specificity of 100% (2,575/2,575), and agreement of 99.9% (2,814/2,816) compared with the results of blood culture. For seven samples with multiple pathogens identified simultaneously during one blood culture investigation, the PCR-MCA assay verified the results of the blood culture, with an agreement rate of 100% for each.Conclusion: The PCR-MCA assay could discover 88.8% of the pathogens in clinical practice, showing excellent diagnostic performance vs. that of blood culture for pathogen detection in patients with suspected BSIs, and would contribute to rapid diagnosis and correct antibiotic administration.

Abstract Background Because of the high prevalence and absence of cure for infection, chronic hepatitis B virus (HBV) infection has been acknowledged as a pressing public health issue. Toll-like receptors (TLRs) activate the human innate immune system and the polymorphisms in TLRs may alter their function. The present study aimed to investigate the association between TLR polymorphisms and disease progression of chronic HBV infection. Methods During the study period, 211 treatment-naïve patients with chronic HBV infection were recruited, and blood samples were collected from each individual. Matrix-assisted laser desorption/ionization time of flight mass spectrometry was employed to genotype the selected TLR polymorphisms after human genome extraction. In addition, HbsAg, TNF-α, and IL-6 levels were quantified using enzyme linked immunosorbent assay (ELISA). Statistical analyses were conducted to investigate the association between TLR polymorphisms and hepatitis activity, liver function parameters, HbsAg level, and cytokine level. Results We did not observe any mutations in rs4986790, rs4986791, and rs5743708 among all study subjects. A logistic regression revealed that mutations in rs3804099 and rs4696480 were associated with milder hepatitis activity. Consistent with the logistic regression, improved liver function parameters and reduced level of both HbsAg and cytokines were also correlated with the mutant carriers of rs3804099 and rs4696480. Conclusions TLR mutations were significantly associated with milder hepatitis activity among patients with chronic HBV infection. Therefore, we conclude that the activation of TLR pathways may further intensify the inflammation of hepatocytes, and leads to progression of disease.

The water-cooled ceramic breeder (WCCB) blanket is a component of the China Fusion Engineering Test Reactor (CFETR). The Reduced Activation Ferrite/Martensite (RAFM) steels are the preferred structural materials for WCCB blanket. As a kind of RAFM steels, China low activation martensitic (CLAM) steel was welded by electron beam welding (EBW), and then quenched-tempered treatment was carried out. The results show that at the welding state, the welding seam was composed of large martensite and δ ferrite and the organization of the heat-affected zone (HAZ) was changed slightly with the different heat input. Moreover, the hardness of welded joints was higher than that of base material (BM), but the impact toughness was very low. After quenched-tempered treatment, the δ ferrite in the weld was eliminated, the residual stress of the test plate decreased as a whole, and the mechanical properties were improved significantly.

The traditional foundry industry has developed rapidly in recently years due to advancements in computer technology. Modifying and designing the feeding system has become more convenient with the help of the casting software, InteCAST. A common method of designing a feeding system is to first design the initial systems, run simulations with casting software, analyze the feedback, and then redesign. In this work, genetic, fruit fly, and interior point optimizer (IPOPT) algorithms were introduced to guide the optimal riser design for the feeding system. The results calculated by the three optimal algorithms indicate that the riser volume has a weak relationship with the modulus constraint; while it has a close relationship with the volume constraint. Based on the convergence rate, the fruit fly algorithm was obviously faster than the genetic algorithm. The optimized riser was also applied during casting, and was simulated using InteCAST. The numerical simulation results reveal that with the same riser volume, the riser optimized by the genetic and fruit fly algorithms has a similar improvement on casting shrinkage. The IPOPT algorithm has the advantage of causing the smallest shrinkage porosities, compared to those of the genetic and fruit fly algorithms, which were almost the same.

To accelerate the large-scale cellular automaton (CA) simulation for grain growth, a parallel CA model for grain growth was developed. The model was implemented based on the compute unified device architecture (CUDA) parallel computing platform. The model was verified by the grain growth of a single crystal and the columnar-to-equiaxed transition (CET) of an Al-7wt% Si specimen of uniform undercooling with a constant cooling rate. The grid independence of the model was verified. The grain growth of a plate-like casting of nickel-based superalloy during directional solidification process was simulated and the obtained results of grain density at each section with different heights were compared with the experimental data. The CET transition of directional solidified Al-7wt% Si cylindrical ingot was simulated. The grain texture and cooling curves were in good agreement with experimental results from the literature. Finally, high parallel performance of the CA model was obtained and evaluated.

Emergence of two-dimensional (2D) materials with atomic-layer structures, such as graphene and MoS2, which have excellent physical properties, provides the opportunity of substituting silicon-based micro/nanoelectronics. An important issue before large-scale applications is the heat dissipation performance of these materials, especially when they are supported on a substrate, as in most scenarios. Thermal transport across the atomic-layer interface is essential to the heat dissipation of 2D materials due to the extremely large contact area with the substrate, when compared with their atomic-scale cross-sections. Therefore, the understanding of the interfacial thermal transport is important, but the characterization is very challenging due to the limitations for temperature/thermal probing of these atomic-layer structures. In this review, widely used characterization techniques for experimental characterization as well as their results are presented. Emphasis is placed on the Raman-based technology for nm and sub-nm temperature differential characterization. Then, we present physical understanding through theoretical analysis and molecular dynamics. A few representative works about the molecular dynamics studies, including our studies on the size effect and rectification phenomenon of the graphene-Si interfaces are presented. Challenges as well as opportunities in the thermal transport study of atomic-layer structures are discussed. Though many works have been reported, there is still much room in both the development of experimental techniques as well as atomic-scale simulations for a clearer understanding of the physical fundamentals of thermal transport across the atomic-layer interfaces, considering the remarkable complexity of physical/chemical conditions at the interface.

The mesoscopic grain model is a multiscale model which takes into account both the dendrite growth mechanism and the vast numerical computation of the actual castings. Due to the pursuit of efficient computation, the mesoscopic grain calculation accuracy is lower than that of dendrite growth model. Improving the accuracy of mesoscopic grain model is a problem to be solved urgently. In this study, referring to the calculation method of solid fraction in microscopic dendrite growth model, a cellular automata model of 3D mesoscopic grain evolution for solid fraction calculated quantitatively at the scale of cell is developed. The developed model and algorithm validation for grain growth simulation is made by comparing the numerical results with the benchmark experimental data and the analytical predictions. The results show that the 3D grain envelopes simulated by the developed model and algorithm are coincident with the shape predicted by the analytical model to a certain extent. Then, the developed model is applied to the numerical simulation of solidification process of nickel-based superalloys, including equiaxed and columnar dendritic grain growth. Our results show good agreement with the related literature.

An efficient one-pot method to generate structurally diverse and medicinally interesting pyrazolone derivatives in good to excellent yields of 51–98% under microwave irradiation and solvent-free conditions has been developed.

B ackground: Red blood cell distribution width (RDW) that describes red blood cell volume heterogeneity is a common laboratory test. Our aim was to focus on th e association between RDW and a c ute pancreatitis associated lung injury (APALI). Methodology: A total of 152 acute pancreatitis (AP) patients who conformed to the criteria w ere included in this study. The demographic data, medical histories and laboratory measures was obtained from each patient on admission, further, the medical histories and biological data were analyzed, retrospectively. Results: Increased RDW at admission was observed in patients with APALI compared with the non-APALI groups. Our results exhibited that RDW was an independent risk factor for APALI after adjusting leukocyte, neutrophil percentage, random blood glucose (RBG), total bilirubin (TB) and total bile acid（TBA）(Crude model) (OR=2.671;CI 95% 1.145-6.230; P=0.023), further adjustment based on Crude model for sex and age did not attenuate the significantly high risk of APALI in patients with AP, RWD still remained a ro les as an independent risk factor for APALI (OR=2.653;CI95 % 1.123-6.138; P=0.026). Conclusions: Our study demonstrate that RDW at admission is associated with APALI and should be considered as an underlying risk factor of APALI.

Cardiac fibrosis is a deleterious consequence of hypertension which may further advance to heart failure and increased matrix metalloproteinase-9 (MMP-9) contributes to the underlying mechanism. Therefore, new therapeutic strategies to attenuate the effects of MMP-9 are urgently needed. In the present study, we characterize salvianolic acid A (SalA) as a novel MMP-9 inhibitor at molecular, cellular and animal level. We expressed a truncated form of MMP-9 which contains only the catalytic domain (MMP-9 CD), and used this active protein for enzymatic kinetic analysis and Biacore detection. Data generated from these assays indicated that SalA functioned as the strongest competitive inhibitor of MMP-9 among 7 phenolic acids from Salvia miltiorrhiza. In neonatal cardiac fibroblast, SalA inhibited fibroblast migration, blocked myofibroblast transformation, inhibited secretion of intercellular adhesion molecule (ICAM), interleukin-6 (IL-6) and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as collagen induced by MMP-9 CD. Functional effects of SalA inhibition on MMP-9 was further confirmed in cultured cardiac H9c2 cell overexpressing MMP-9 in vitro and in heart of spontaneously hypertensive rats (SHR) in vivo. Moreover, SalA treatment in SHR resulted in decreased heart fibrosis and attenuated heart hypertrophy. These results indicated that SalA is a novel inhibitor of MMP-9, thus playing an inhibitory role in hypertensive fibrosis. Further studies to develop SalA and its analogues for their potential clinical application of cardioprotection are warranted.

Glucose transporter 4 (GLUT4) is a principal glucose transporter in response to insulin, and impaired translocation or decreased expression of GLUT4 is believed to be one of the major pathological features of type 2 diabetes mellitus (T2DM). Therefore, induction of GLUT4 translocation or/and expression is a promising strategy for anti-T2DM drug discovery. Here we report that the natural product (+)-Rutamarin (Rut) functions as an efficient dual inducer on both insulin-induced GLUT4 translocation and expression. Rut-treated 3T3-L1 adipocytes exhibit efficiently enhanced insulin-induced glucose uptake, while diet-induced obese (DIO) mice based assays further confirm the Rut-induced improvement of glucose homeostasis and insulin sensitivity in vivo. Subsequent investigation of Rut acting targets indicates that as a specific protein tyrosine phosphatase 1B (PTP1B) inhibitor Rut induces basal GLUT4 translocation to some extent and largely enhances insulin-induced GLUT4 translocation through PI3 kinase-AKT/PKB pathway, while as an agonist of retinoid X receptor α (RXRα), Rut potently increases GLUT4 expression. Furthermore, by using molecular modeling and crystallographic approaches, the possible binding modes of Rut to these two targets have been also determined at atomic levels. All our results have thus highlighted the potential of Rut as both a valuable lead compound for anti-T2DM drug discovery and a promising chemical probe for GLUT4 associated pathways exploration.

The chemical similarity of cellulose and chitin supports the idea that their corresponding hydrolytic enzymes would bind β-1,4-linked glucose residues in a similar manner. A structural and mutational analysis was performed for the plant cellulolytic enzyme BGlu1 from Oryza sativa and the insect chitinolytic enzyme OfHex1 from Ostrinia furnacalis. Although BGlu1 shows little amino-acid sequence or topological similarity with OfHex1, three residues (Trp(490), Glu(328), Val(327) in OfHex1, and Trp(358), Tyr(131) and Ile(179) in BGlu1) were identified as being conserved in the +1 sugar binding site. OfHex1 Glu(328) together with Trp(490) was confirmed to be necessary for substrate binding. The mutant E328A exhibited a 8-fold increment in K(m) for (GlcNAc)(2) and a 42-fold increment in K(i) for TMG-chitotriomycin. A crystal structure of E328A in complex with TMG-chitotriomycin was resolved at 2.5 Å, revealing the obvious conformational changes of the catalytic residues (Glu(368) and Asp(367)) and the absence of the hydrogen bond between E328A and the C3-OH of the +1 sugar. V327G exhibited the same activity as the wild-type, but acquired the ability to efficiently hydrolyse β-1,2-linked GlcNAc in contrast to the wild-type. Thus, Glu(328) and Val(327) were identified as important for substrate-binding and as glycosidic-bond determinants. A structure-based sequence alignment confirmed the spatial conservation of these three residues in most plant cellulolytic, insect and bacterial chitinolytic enzymes.

BACKGROUND: Abundant evidence indicates that chicken reproduction is strictly regulated by the hypothalamic-pituitary-gonad (HPG) axis, and the genes included in the HPG axis have been studied extensively. However, the question remains as to whether any other genes outside of the HPG system are involved in regulating chicken reproduction. The present study was aimed to identify, on a genome-wide level, novel genes associated with chicken reproductive traits. METHODOLOGY/PRINCIPAL FINDING: Suppressive subtractive hybridization (SSH), genome-wide association study (GWAS), and gene-centric GWAS were used to identify novel genes underlying chicken reproduction. Single marker-trait association analysis with a large population and allelic frequency spectrum analysis were used to confirm the effects of candidate genes. Using two full-sib Ningdu Sanhuang (NDH) chickens, GARNL1 was identified as a candidate gene involved in chicken broodiness by SSH analysis. Its expression levels in the hypothalamus and pituitary were significantly higher in brooding chickens than in non-brooding chickens. GWAS analysis with a NDH two tail sample showed that 2802 SNPs were significantly associated with egg number at 300 d of age (EN300). Among the 2802 SNPs, 2 SNPs composed a block overlapping the GARNL1 gene. The gene-centric GWAS analysis with another two tail sample of NDH showed that GARNL1 was strongly associated with EN300 and age at first egg (AFE). Single marker-trait association analysis in 1301 female NDH chickens confirmed that variation in this gene was related to EN300 and AFE. The allelic frequency spectrum of the SNP rs15700989 among 5 different populations supported the above associations. Western blotting, RT-PCR, and qPCR were used to analyze alternative splicing of the GARNL1 gene. RT-PCR detected 5 transcripts and revealed that the transcript, which has a 141 bp insertion, was expressed in a tissue-specific manner. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that the GARNL1 gene contributes to chicken reproductive traits.

This study investigates the structural effects on the cross-plane thermal conductivity of Li4Ti5O12-based anode active material. Three structures are investigated: a basic structure consisting of LiBr/LiCl/Li4Ti5O12, polyvinylidene difluoride, and Super P (sample #1); a structure without Li4Ti5O12 (sample #2); and a structure without LiBr/LiCl (sample #3). Despite its high porosity level (77%), sample #1 exhibits higher thermal conductivity than sample #3 (64% porosity) in both air and vacuum conditions, potentially due to the extra structural bonding provided by LiBr/LiCl. The observed difference in cross-plane thermal conductivity between air and vacuum conditions provides insights into the configuration of the anode's active material in the heat transfer direction. The lower limit corresponds to the parallel thermal circuit configuration of active material and air, which is the product of the sample's porosity and thermal conductivity of air. Our analysis suggests that in sample #2, the anode's active material and air inside the pores demonstrate a more serial configuration, while in sample #3, they exhibit a more parallel configuration in the heat transfer direction. However, the thermal conductivity difference observed for sample #1 falls below the theoretical lower bound indicating significant thermal radiation within the pores. Furthermore, the in-plane thermal conductivity is predominantly controlled by the copper foil. Sample #2 exhibits the lowest in-plane thermal conductivity. This is attributed to the severe oxidization of the copper foil by LiBr/LiCl, which is confirmed by structure characterization. [ABSTRACT FROM AUTHOR]