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Mitochondrial dysfunction is one of hallmarks in pathophysiology of prion disease and other neurodegenerative diseases. Various metabolic dysfunctions are identified and considered to contribute to the progression of some types of neurodegenerative diseases. In this study, we evaluated the status of glycolysis pathway in prion infected rodent and cell models. The levels of the key enzymes, hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) were significantly increased, accompanying with markedly downregulated mitochondrial complexes. Double stained IFAs revealed that the increased HK2 and PFK distributed widely in GFAP-, Iba1- and NeuN-positive cells. We also identified increased levels of AMP-activated protein kinase (AMPK) and the downstream signaling. Changes of AMPK activity in prion infected cells by the AMPK-specific inhibitor or activator induced the corresponding alterations not only in the downstream signaling, but also the expressions of three key kinases in glycolysis pathway and the mitochondrial complexes. Transient removal or complete clearance of prion propagation in the prion infected cells partially but significantly reversed the increases of the key enzymes in glycolysis, the upregulation of AMPK signaling pathway, and the decreases of the mitochondrial complexes. Measurements of the cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) showed lower OCR and higher ECAR in prion infected cell line, which were sufficiently reversed by clearance of prion propagation. Those data indicate a metabolic reprogramming from oxidative phosphorylation to glycolysis in the brains during the progression of prion disease. Accumulation of PrPSc is critical for the switch to glycolysis, largely via activating AMPK pathway.

Early and accurate diagnosis of human prion diseases is a long-standing difficulty. Currently, the definitive diagnosis of human prion diseases relies on pathognomonic histological features or PrPSc detection of patients' brain tissue biopsy or autopsy samples, which is not feasible in most cases. Therefore, clinical diagnosis mainly relies on the combinations of the patient’s clinical symptoms. MRI and EEG are used to check for brain damage and detect surrogate markers such as the 14-3-3 protein in Cerebrospinal fluid (CSF), but this is often challenging. In recent years, the development of in vitro cell-free conversion techniques, such as technologies protein misfolding cyclic amplification (PMCA) and real-time quaking-induced conversion (RT-QuIC), have extensively promoted the diagnosis of human prion diseases. PMCA has high diagnostic accuracy in the blood, CSF, and urine samples of variant creutzfeldt–jakob disease (vCJD) patients. Again, RT-QuIC has high diagnostic accuracy for cerebrospinal fluid, olfactory mucosa, and skin samples of sporadic Creutzfeldt Jakob Disease (sCJD) patients. Applying these two technologies is of great significance to the early clinical diagnosis of human prion diseases and the reduction of blood-borne and iatrogenic transmission of prion.

Prion disease (PrD) and Parkinson's disease (PD) are neurodegenerative diseases characterized by aggregation of misfolded proteins in brain tissues, including protease-resistant prion protein (PrPSc) in PrD and α-synuclein in PD. In recent years, overlap of these two proteins has attracted increased attention, and cross-seeding of prion proteins by aggregated α-synuclein has been proposed. However, the changes in α-synuclein after prion infection are still unclear. In this study, we showed that α-synuclein expression was significantly decreased in the brains of prion-infected rodent models, in the SMB-S15 cell line, which exhibits persistent prion replication, and in the brains of humans with PrDs. Meanwhile, α-synuclein phosphorylated at serine 129(p(S129)-α-synuclein) was significantly increased in the brains of scrapie-infected mice and prion-infected SMB-S15 cells. The increased p(S129)-α-synuclein colocalized with GFAP- and NeuN-positive cells in the brains of scrapie-infected mice. p(S129)-α-synuclein was also observed in the cytoplasm of SMB-S15 and HEK-293 cells transiently expressing an abnormal form of prion protein (Cyto-PrP). Molecular interactions between PrP and α-synuclein were detected in recombinant proteins, normal and prion-infected brain tissues, and cultured cells. The increased p(S129)-α-synuclein colocalized with PrP signals from prion-infected SMB-S15 and HEK-293 cells expressing Cyto-PrP. Moreover, increased morphological colocalization of p(S129)-α-synuclein with mitochondrial markers was also detected in the two cell types. Our results indicate that prion replication and accumulation in cells and brains induce hyperphosphorylation of α-synuclein, particularly at S129, which may aggravate mitochondrial damage and facilitate α-synuclein aggregation in the central nervous system tissues from PrDs.

Human genetic prion diseases (gPrDs) are directly associated with mutations and insertions in the PRNP (Prion Protein) gene. We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020. Nineteen different subtypes were identified and gPrDs accounted for 10.9% of all diagnosed PrDs within the same period. Some subtypes of gPrDs showed a degree of geographic association. The age at onset of Chinese gPrDs peaked in the 50–59 year group. Gerstmann–Sträussler–Scheinker syndrome (GSS) and fatal familial insomnia (FFI) cases usually displayed clinical symptoms earlier than genetic Creutzfeldt–Jakob disease (gCJD) patients with point mutations. A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients. None of the E196A gCJD patients reported a family history. The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD (sCJD). EEG examination was not sensitive for gPrDs. sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients. CSF 14-3-3 positivity was frequently detected in gCJD patients. Increased CSF tau was found in more than half of FFI and T188K gCJD cases, and an even higher proportion of E196A and E200K gCJD patients. 63.6% of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC. GSS and FFI cases had longer durations than most subtypes of gCJD. This is one of the largest studies of gPrDs in East Asians, and the illness profile of Chinese gPrDs is clearly distinct. Extremely high proportions of T188K and E196A occur among Chinese gPrDs; these mutations are rarely reported in Caucasians and Japanese.

Activation of chemokine IP10, also named as CXCL10, and its receptor CXCR3 in CNS is described in some neurodegenerative diseases. Our previous study has also demonstrated an increased brain IP10 levels in several scrapie infected rodent models. However, the detailed alteration of IP10/CXCR3 signaling in CNS during prion infection remains unsettled. Here, we found the increased IP10 signals in the brains of scrapie infected mice mainly localized in the neurons using various methodologies. The levels of CXCR3 were markedly increased in brains of the scrapie infected mice and in the prion infected cell line SMB-S15. The increased CXCR3 is mainly distributed in neurons and activated microglia. Obviously morphological colocalizations of PrPC/PrPScwith IP10 and CXCR3 in the brains of scrapie infected mice were observed in the assays of immunohistochemistry (IHC) and immunofluorescence. Additionally, IHC analysis with whole brain sections demonstrated that the increased IP10 and CXCR3 accumulations occurred in the brain regions with more PrPScdeposits. Co-immunoprecipitation and biomolecular interaction assays identified the evidence for the molecular interactions of PrP with IP10 and CXCR3. Compared to the normal partner cell line SMB-PS, a larger amount of IP10 accumulated inside prion infected SMB-S15 cells. Suppression of prion replication in SMB-S15 cells by added resveratrol reverted the pattern of accumulation and secretion of cellular IP10 to that observed in SMB-PS cells. Our data here demonstrate an activation of IP10/CXCR3 signaling in prion-infected brain tissues that coincide with deposited PrPSc. Modulation of brain IP10/CXCR3 signaling is potential therapeutic target for reducing the progression of prion diseases.

Activation of chemokine IP10, also named as CXCL10, and its receptor CXCR3 in CNS is described in some neurodegenerative diseases. Our previous study has also demonstrated an increased brain IP10 levels in several scrapie infected rodent models. However, the detailed alteration of IP10/CXCR3 signaling in CNS during prion infection remains unsettled. Here, we found the increased IP10 signals in the brains of scrapie infected mice mainly localized in the neurons and the activated microglia using various methodologies. The levels of CXCR3 were markedly increased in brains of the scrapie infected mice and in the prion infected cell line SMB-S15. The increased CXCR3 mainly distributed in neurons. Obviously morphological colocalizations of PrP/PrPScwith IP10 and CXCR3 in the brains of scrapie infected mice were observed in the assays of immunohistochemistry (IHC) and immunofluorescence. Additionally, IHC analysis with whole brain sections demonstrated that the increased IP10 and CXCR3 accumulated in the brain regions with more PrPScdeposits. Co-immunoprecipitation and biomolecular interaction assays identified the evidence for the molecular interactions of PrP with IP10 and CXCR3. Compared to the normal partner cell line SMB-PS, the more portion of IP10 accumulated insides of prion infected SMB-S15 cells. Removal of prion replication in SMB-S15 cells by resveratrol converted the pattern of the accumulation and secretion of cellular IP10. Our data here demonstrate an activation of IP10/CXCR3 signaling in the brain tissues of prion infection, highly coincidental with PrPScdeposit. Modulation of brain IP10/CXCR3 signaling is potential therapeutic target for reducing the progression of prion diseases.

Grain characteristics of rolled 1235 aluminum alloy were studied by EBSD. The effects of hot rolling, cold rolling and rolling deformation on grain boundaries and grain size of the metal were studied as well. The content of high-angle boundaries was low by 16.48 % in 50 % hot-rolled 1235 aluminum alloy. The complete dynamic recrystallization occurred, and grains were coarse. During 90 % hot rolling, the low-angle boundaries turned into high-angle boundaries constantly. The content of high-angle boundaries was higher by 40.16 %. Coarse grains broke into fine grains, and grew into medium grains. In the 90 % cold-rolled alloy, the trace shape of high-angle boundary was irregular. The lattice distortion was large, providing the energy needed in recrystallization during recrystallization annealing.

Mitophagy is an important process for removing damaged mitochondria in cells, the dysfunction of which has been directly linked to an increasing number of neurodegenerative disorders. However, the details of mitophagy in prion diseases still need to be deeply explored. In this study, we identified more autophagosomes and large swelling mitochondria structures in the prion-infected cultured cell line SMB-S15 by transmission electron microscopy, accompanying the molecular evidence of activated autophagic flux. Western blots illustrated that the levels of Pink1 and Parkin, particularly in the mitochondrial fraction, were increased in SMB-S15 cells, whereas the levels of mitochondrial membrane proteins TIMM44, TOMM20, and TIMM23 were decreased. The amount of whole polyubiquitinated proteins decreased, but that of phosphor-polyubiquitinated proteins increased in SMB-S15 cells. The level of MFN2 in SMB-S15 cells were down-regulated, but its polyubiquitinated form was up-regulated. Knockdown of the expressions of Pink1 and Parkin by the individual SiRNAs in SMB-S15 cells reduced autophagic activity but did not seem to influence the expressions of TOMM20 and TIMM23. Moreover, we also demonstrated that the brain levels of Pink1 and Parkin in the mice infected with scrapie strains 139A and ME7 were remarkably increased at the terminal stage of the disease by Western blot and immunohistochemical (IHC) assays. Immunofluorescent assays revealed that Pink1 signals widely colocalized with GAFP-, Iba1-, and NeuN-positive cells in the brains of scrapie-infected mice. IHC assays with serial sections of the brain tissues infected with agents 139A and ME7 showed more Pink1- and Parkin-positive cells located at the areas with more PrP

PRNP gene encodes PrP protein, which is conservative among different species and associates with the susceptibility of prion disease. In this report, we cloned and sequenced the full-length PRNP gene of Vulpes corsac in Qinghai plateau, China. The amino acid sequence of Vulpes corsac PrP showed 100% homology with those of the other three species of foxes. The taxa relationship of Vulpes corsac PrP with other species of animals, including human, canine, bovine, cervus, capra, ovis, camelus, felis, Mustela, mouse and hamster were also analysed.

To describe the global profiles of acetylated proteins in the brains of scrapie agents 139A- and ME7-infected mice collected at mid-early, mid-late, and terminal stages.The acetylated proteins from the cortex regions of scrapie agent (139A- and ME7)-infected mice collected at mid-early (80 days postinfection, dpi), mid-late (120 dpi), and terminal (180 dpi) stages were extracted, and the global profiles of brain acetylated proteins were assayed with proteomic mass spectrometry. The proteins in the infected mice showing 1.5-fold higher or lower levels than that of age-matched normal controls were considered as differentially expressed acetylated peptides (DEAPs).A total of 118, 42, and 51 DEAPs were found in the brains of 139A-80, 139A-120, and 139A-180 dpi mice, respectively. Meanwhile, 390, 227, and 75 DEAPs were detected in the brains of ME7-80, ME7-120, and ME7-180 dpi mice, respectively. The overwhelming majority of DEAPs in the mid-early stage were down-regulated, and more portions of DEAPs in the mid-late and late stages were up-regulated. Approximately 22.1% (328/1,485) of acetylated peptides mapped to 74 different proteins were mitochondrial associated. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 39 (80 dpi), 13 (120 dpi), and 10 (180 dpi) significantly changed pathways in 139A-infected mice. Meanwhile, 55, 25, and 18 significantly changed pathways were observed in the 80, 120, and 180 dpi samples of 139A- and ME7-infected mice (Our data here illustrated the changes in the global profiles for brain acetylated proteins during prion infection, showing remarkably inhibited acetylation in the early stage and relatively enhanced acetylation in the late stage.

Nowadays, almost all the online orders were placed through screened devices such as mobile phones, tablets, and computers. With the rapid development of the Internet of Things (IoT) and smart appliances, more and more screenless smart devices, e.g., smart speaker and smart refrigerator, appear in our daily lives. They open up new means of interaction and may provide an excellent opportunity to reach new customers and increase sales. However, not all the items are suitable for screenless shopping, since some items' appearance play an important role in consumer decision making. Typical examples include clothes, dolls, bags, and shoes. In this paper, we aim to infer the significance of every item's appearance in consumer decision making and identify the group of items that are suitable for screenless shopping. Specifically, we formulate the problem as a classification task that predicts if an item's appearance has a significant impact on people's purchase behavior. To solve this problem, we extract multi-modal features from three different views, and collect a set of necessary labels via crowdsourcing. We then propose an iterative semi-supervised learning framework with a carefully designed multi-modal enhancement module. Experimental results verify the effectiveness of the proposed method.

C23H15ClCuN4O3, monoclinic, P21/c (no. 14), a = 10.63346(14) Å, b = 17.99387(15) Å, c = 11.60320(16) Å, β = 116.2165(17)°, V = 1991.74(5) Å3, Z = 4, R gt (F) = 0.0315, wR ref(F 2) = 0.0898, T = 293(2) K.

Obstructive sleep apnea syndrome (OSAS) was suggested to exert an effect on renal function. However, the specific mechanism was still unknown. We try to find the association among OSAS, adiponectin, and cystatin C and the effect of adiponectin on renal function in OSAS patients. Seventeen healthy men and seventy-three men which only had OSAS were included in the end. Apnea-hypopnea index (AHI), oxygen desaturation index (ODI), the percentage of total sleep time spent with SpO2

With an increasing population and changing diet structure, summer maize is increasingly becoming an important energy crop in China. However, traditional farmer practices for maize production are inefficient and unsustainable. To ensure food security and sustainable development of summer maize production in China, an improved, more sustainable farmer management system is needed. Establishing this system requires a comprehensive understanding of the limitations of current farming practice and the ways it could be improved. In our study, 235 plots from three villages in the North China Plain (NCP) were monitored. Maize production on farms was evaluated; our results showed that the maize yield and nitrogen partial factor productivity (PFPN) were variable on smallholder farms at 6.6–13.7 t ha−1 and 15.4–88.7 kg kg−1, respectively. Traditional farming practices also have a large environmental impact (nitrogen surplus: −64.2–323.78 kg ha−1). Key yield components were identified by agronomic diagnosis. Grain yield depend heavily on grain numbers per hectare rather than on the 1000-grain weight. A set of improved management practices (IP) for maize production was designed by employing a boundary line (BL) approach and tested on farms. Results showed that the IP could increase yield by 18.4% and PFPN by 31.1%, compared with traditional farmer practices (FP), and reduce the nitrogen (N) surplus by 57.9 kg ha−1. However, in terms of IP effect, there was a large heterogeneity among different smallholder farmers' fields, meaning that, precise technologies were needed in different sites especially for N fertilizer management. Our results are valuable for policymakers and smallholder farmers for meeting the objectives of green development in agricultural production.

North China Plain (NCP) is the primary winter wheat production region in China, characterized by smallholder farming systems. Whereas the winter wheat average yield of smallholder farmers is currently low, the yield potential and limiting factors driving the current yield gap remain unclear. Therefore, increasing the wheat yield in NCP is essential for the national food security. This study monitored wheat yield, management practices and soil nutrient data in 132 farmers' fields of Xushui County, Baoding City, Hebei Province during 2014–2016. These data were analyzed using variance and path analysis to determine the yield gap and the contribution of yield components (i.e., spikes per hectare, grain number per spike and 1000-grain weight) to wheat yield. Then, the limiting factors of yield components and the optimizing strategies were identified by a boundary line approach. The results showed that the attainable potential yield for winter wheat was 10 514 kg ha−1. The yield gaps varied strongly between three yield groups (i.e., high, middle and low), which were divided by yield level and contained 44 farmers in each group, and amounted to 2493, 1636 and 814 kg ha−1, respectively. For the three yield components, only spikes per hectare was significantly different (P6.598 × 06 ha−1), the seeding rate should range from 210–300 kg ha−1, seeding date should range from 3th to 8th October, and basal N input should range from 90–180 kg ha−1. Compared to these reasonable ranges of management measures, most of the farmers' practices were not suitable, and both lower and higher levels of management existed. It is concluded that the strategies for optimizing yield components could be achieved by improving wheat seeding quality and optimizing farmers' nutrient management practices in the NCP.

The microstructural evolution is complex and time-varying in the practice hot forming process of alloy parts. Therefore, accurately online optimizing forming parameters and controlling microstructural evolution are the urgent tasks. In this work, an action-dependent heuristic dynamic programming (ADHDP) is developed to online optimize processing parameters during hot deformation of alloys. The ADHDP is based on adaptive dynamic programming and only contains action/critic neural networks (ANN/CNN). ANN is utilized to determine the next control signals (processing parameters) of hot deformation, while CNN is used to obtain the approximation of cost-to-go function. The weights of these neural networks are online-updated by back-propagation algorithm. The control goals include the recrystallization volume fraction and average grain size. The proposed ADHDP method is successfully applied to online optimize processing parameters of GH4169 superalloy during hot deformation, and its effectiveness is verified by numerical simulations. According to the optimized processing parameters, the hot compressive tests of GH4169 superalloy are conducted to further verify the validity of the developed method. Furthermore, the microstructures, which are obtained by the proposed method, are more uniform and fine than those obtained by the traditional processing without online optimization.

The fungal cell wall is very important for cell growth and survival during stress, and the target of rapamycin (TOR) pathway plays a major role in regulating cell growth in response to environmental cues. Ganoderma lucidum is an important edible and medicinal fungus, and the function of TOR in this organism remains unclear. As shown in the present study, the TOR pathway regulates cell wall integrity (CWI) in G. lucidum. Inhibition of TOR signaling by RNA interference (RNAi) or rapamycin treatment reduced the growth of G. lucidum mycelia, increased contents of the cell wall components chitin and β-1,3-glucan, and increased cell wall thickness. Furthermore, inhibition of TOR signaling enhanced the relative level of phosphorylated Slt2, a member of the MAPK cascade involved in CWI signaling. Moreover, when treated with rapamycin, significantly lower chitin and β-1,3-glucan contents were observed in Slt2-silenced strains than in WT strains, indicating that TOR regulates the synthesis of these cell wall components through the Slt2-MAPK pathway. These results indicate a potential relationship between TOR signaling and CWI signaling. Additionally, participation of Slt2-MAPK in TOR-mediated regulation of cell wall component production has not previously been reported in a microorganism.

To observe the clinical effect of platelet rich plasma (PRP) combined with β tricalcium phosphate bioceramic bone in the treatment of non traumatic necrosis of the femoral head in ARCO stageⅡ.From January 2017 to December 2018, 100 patients (160 hips) with ARCO stageⅡnon traumatic necrosis of the femoral head were divided into PRP group and control group. In PRP group, 50 patients (80 hips), 22 males and 28 females, aged from 18 to 65 (43.47± 7.23) years, with a course of 4 to 18 (15.8±2.9) months, underwent core decompression and bone grafting combined with PRP implantation. There were 50 cases (80 hips) in the control group, including 27 males and 23 females, aged 20 to 63 (45.72± 7.43) years, and the course of disease was 6 to 19 (14.9±3.8) months. Hip X-ay film was followed up after operation. Harris score and VAS score were used to evaluate the curative effect, and the survival rate of hip joint was recorded.All patients had good wound healing, no infection, thrombosis and other complications. All patients were followed up for 12 to 14 (12.0±0.4) months. Twelve months after operation, the image expression of PRP group was better than that of control group(Platelet-rich plasma(PRP) combined with artificialbone for core decompression and bone grafting can change the situation of simple artificial bone implantation and uncertain curative effect, improve the success rate of this operation, effectively reduce the collapse rate of femoral head necrosis in the early and middle stage, delay or even avoid hip replacement.

BackgroundAcetylation is a reversible post-translational modification in eukaryotic and prokaryotic cells, actively participating in the regulation for biological functions and in the pathogenesis of diseases.MethodsThe acetylated proteins from the cortex regions of scrapie agents 139A- and ME7-infected mice collected at mid-early (80 days post-infection, dpi), mid-late (120 dpi) and terminal stage (180 dpi) were extracted. The global profiles of the brain acetylated proteins were assayed with proteomic mass spectrometry. The acetylated peptides whose levels were >1.5-fold higher or lower than that of age-matched normal controls were considered as differentially expressed acetylated peptides (DEAPs).ResultsA total of 1,485 acetylated peptides were identified. 118, 42 and 51 DEAPs were in the brains of 139A-80 dpi, 120 dpi and 180 dpi, while 390, 227 and 75 DEAPs were in those of ME7-80 dpi, 120 dpi and 180 dpi, respectively. Overwhelming majority of the DEAPs in mid-early stage was down-regulated, while more portions of DEAPs in mid-late and late stage were up-regulated. Approximately 22.1% (328/1485) acetylated peptides were mitochondrial associated, which were mapped to 74 different proteins. Among them, 44 (59.5%) proteins showed differentially expressed at least at one tested time-point. KEEG pathways analysis identified 39, 13, 10 and 55, 25, 18 pathways in the samples of 80, 120 and 180 dpi of 139A- and ME7-infected mice as significantly changed (PConclusionCollectively, Our data here illustrated a picture of global acetylation for brain proteins during prion infection, showing remarkably inhibiting acetylation in the early stage and relatively enhanced acetylation in the late stage.

The definite diagnosis of human and animal prion diseases depends on the examination of special pathological changes and/or detection of PrPWe prepared a PrP-specific polyclonal antibody (pAb P54) in aWestern blot illustrated that the newly prepared pAb P54 could react with recombinant PrP protein, normal brain PrPThe newly prepared pAb P54 demonstrated reliable specificity and sensitivity and, thus, may have potential applications not only in studies of prion biology but also in the diagnosis of human and experimental rodent prion diseases.

Ganoderma lucidum, which contains many pharmacologically active compounds, is regarded as a traditional medicinal fungus. Nevertheless, the scarcity of basic research limits the commercial value and utilization of G. lucidum. As a class of highly conserved, phosphopeptide-binding proteins present in all eukaryotes, 14-3-3 proteins play vital roles in controlling multiple physiological processes, including signal transduction, primary metabolism, and stress responses. However, knowledge of the roles of 14-3-3 proteins in Basidiomycetes is sparse. In this article, two homologs of 14-3-3 proteins, encoded by the two distinct genes GlBmh1 and GlBmh2, were distinguished in G. lucidum. We found that GlBmh1 and GlBmh2 were expressed at various developmental stages, including in vegetative mycelium cultivated on solid medium and in primordia and fruiting bodies. Moreover, we constructed GlBmh1 single-silenced strains, GlBmh2 single-silenced strains, and 14-3-3 double-silenced mutants for further study. When GlBmh1 and GlBmh2 were inhibited by RNA interference, the growth rate of mycelia was decreased, and the distance between the aerial hyphal branches was reduced; responses to various abiotic stresses such as oxidants and cell wall and osmotic stressors were also changed. Furthermore, the contents of secondary metabolite ganoderic acids (GAs) were increased after GlBmh1 and GlBmh2 were simultaneously silenced. Taken together, we provide evidence that implicates potential roles for the two 14-3-3 proteins in affecting growth and GA biosynthesis, thereby providing new insights into the basic functions of 14-3-3 proteins in G. lucidum.

The Monte Carlo method has been used to study the magnetic and thermodynamic properties of a hexagonal ferrimagnetic Ising nanoparticle with spin-3/2 inner core surrounded by spin-1 surface shell layers. The effects of exchange couplings and crystal-fields on the compensation behaviors and critical phenomena of the system have been investigated in detail. Many types of the magnetization curves have been found, depending on the competitions among the exchange couplings, the crystal-fields and the temperature. The phase diagrams for different exchange couplings and crystal-fields have been also obtained. In Particular, we have discovered the double and triple hysteresis loops for certain physical parameters in the present system. An excellent agreement has been achieved from the comparison between our results and the previous studies.

SnO2 nanofibers were synthesized by electrospinning and modified with Co3O4 via impregnation in this work. Chemical composition and morphology of the nanofibers were systematically characterized, and their gas sensing properties were investigated. Results showed that Co3O4 modification significantly enhanced the sensing performance of SnO2 nanofibers to ethanol gas. For a sample with 1.2 mol% Co3O4, the response to 100 ppm ethanol was 38.0 at 300 °C, about 6.7 times larger than that of SnO2 nanofibers. In addition, the response/recovery time was also greatly reduced. A power-law dependence of the sensor response on the ethanol concentration as well as excellent ethanol selectivity was observed for the Co3O4/SnO2 sensor. The enhanced ethanol sensing performance may be attributed to the formation of p-n heterojunctions between the two oxides.

In this study, an in vitro ligation method was developed to assemble a full-length infectious cDNA clone of the Zika virus (ZIKV). Four contiguous cDNA subclones covering the complete ZIKV genome were constructed with unique BglI restriction sites at the ends of each fragment. The BglI restriction sites only allow in vitro ligation to happen between interconnecting restriction sites from adjacent cDNA fragments, resulting in an intact full-length cDNA of ZIKV. RNA transcripts derived from the full-length cDNA were infectious. The recombinant virus replicated as efficiently as the wild-type virus with similar growth kinetics and plaque morphologies in Vero and C6/36 cells. Both viruses were inhibited by NITD008 treatment. This in vitro ligation method will facilitate manipulation of the viral genome through genetic modifications of four separated subclones of ZIKV for the rapid and rational development of candidate vaccines and viral replication study.

Obstructive sleep apnea syndrome (OSAS) is reported to have an association with bone mineral density (BMD). However, the underlying mechanism is far from clear. The aim of this study was to investigate the relationship between OSAS, bone turnover markers, and BMD and to evaluate the effect of adiponectin on BMD in patients with OSAS. Seventy-one male patients with OSAS and 13 male control subjects were enrolled in this study. Serum adiponectin, calcium, phosphorus, 25-hydroxyvitamin-D3, β-isomerized form C-terminal telopeptide of type I collagen, osteocalcin, and procollagen type 1 N-propeptide were measured in all subjects, and BMD was evaluated by dual-energy X-ray absorptiometry (DEXA) in the lumbar spine (L1–L4), the femoral neck, and the hip total. No statistically significant differences were found between the studied groups in terms of demographic data and bone turnover markers. Serum adiponectin significantly decreased with the aggravation of OSAS. Compared with subjects without OSAS, those with OSAS had a higher hip total BMD and t scores (p = 0.027 and p = 0.028). The significant negative association was found between serum adiponectin levels and hip total BMD. After adjusting for confounders, adiponectin as well as oxygen desaturation index (ODI) significantly predicted the hip total BMD (β = −0.232, p = 0.005 and β = 0.226, p = 0.037). In male subjects, the presence of obstructive sleep apnea syndrome is associated with higher bone mineral density of the hip. These findings suggest that serum adiponectin may be an underlying mediator for BMD in OSAS.

Flammulina velutipes is a well-known edible mushroom cultivated all over the world. However, because of the low transformation frequency, the expensive instruments required, and the complicated, time-consuming procedures necessary, there is insufficient genetic research on F. velutipes. In this study, we report a liposome-mediated transformation (LMT) system for the genetic transformation of F. velutipes. Using the LMT system, we obtained 82 ± 4 stable F. velutipes transformants per 105 protoplasts, which is a clear increase in transformation frequency compared to the other methods used. We were able to detect the expression of an EGFP reporter gene in the F. velutipes transformants using fluorescence imaging assays. Furthermore, we used this method to transfer the laccase gene into F. velutipes and found that the transcriptional level and enzymatic activity increased in these transformants. Mitotic stability analysis showed that all of the selected transformants remained mitotically stable, even after five successive rounds of sub-culturing. These results demonstrate a new transgenic approach that will facilitate F. velutipes research.

The sequence variation within the capsid proteins occurs frequently in the infection of susceptible tissue cultures, reflecting the high levels of genetic diversity of FMDV. A systematic study for the functional significance of isolate-specific residues in VP0 and VP3 of FMDV PanAsia-1 strains suggested that the interaction of amino acid side chains between the N terminus of VP4 and several potential domains of VP1-3 had cascading effects on the viability and developmental characteristics of progeny viruses. Y2079H in VP0 of the indicated FMDVs could affect plaque size and pathogenicity, as well as acid sensitivity correlated with NH4Cl resistance, whereas there was no inevitable correlation in viral plaque and acid-sensitive phenotypes. The high affinity of non-integrin-dependent FMDVs for heparin might be explained by the differences in structures of heparan sulfate proteoglycans on the surfaces of different cell lines. These results may contribute to our understanding of the distinct phenotypic properties of FMDV in vitro and in vivo., The presence of sequence divergence through adaptive mutations in the major capsid protein VP1, and also in VP0 (VP4 and VP2) and VP3, of foot-and-mouth disease virus (FMDV) is relevant to a broad range of viral characteristics. To explore the potential role of isolate-specific residues in the VP0 and VP3 coding regions of PanAsia-1 strains in genetic and phenotypic properties of FMDV, a series of recombinant full-length genomic clones were constructed using Cathay topotype infectious cDNA as the original backbone. The deleterious and compensatory effects of individual amino acid substitutions at positions 4008 and 3060 and in several different domains of VP2 illustrated that the chain-based spatial interaction patterns of VP1, VP2, and VP3 (VP1-3), as well as between the internal VP4 and the three external capsid proteins of FMDV, might contribute to the assembly of eventually viable viruses. The Y2079H site-directed mutants dramatically induced a decrease in plaque size on BHK-21 cells and viral pathogenicity in suckling mice. Remarkably, the 2079H-encoding viruses displayed a moderate increase in acid sensitivity correlated with NH4Cl resistance compared to the Y2079-encoding viruses. Interestingly, none of all the 16 rescued viruses were able to infect heparan sulfate-expressing CHO-K1 cells. However, viral infection in BHK-21 cells was facilitated by utilizing non-integrin-dependent, heparin-sensitive receptor(s) and replacements of four uncharged amino acids at position 3174 in VP3 of FMDV had no apparent influence on heparin affinity. These results provide particular insights into the correlation of evolutionary biology with genetic diversity in adapting populations of FMDV. IMPORTANCE The sequence variation within the capsid proteins occurs frequently in the infection of susceptible tissue cultures, reflecting the high levels of genetic diversity of FMDV. A systematic study for the functional significance of isolate-specific residues in VP0 and VP3 of FMDV PanAsia-1 strains suggested that the interaction of amino acid side chains between the N terminus of VP4 and several potential domains of VP1-3 had cascading effects on the viability and developmental characteristics of progeny viruses. Y2079H in VP0 of the indicated FMDVs could affect plaque size and pathogenicity, as well as acid sensitivity correlated with NH4Cl resistance, whereas there was no inevitable correlation in viral plaque and acid-sensitive phenotypes. The high affinity of non-integrin-dependent FMDVs for heparin might be explained by the differences in structures of heparan sulfate proteoglycans on the surfaces of different cell lines. These results may contribute to our understanding of the distinct phenotypic properties of FMDV in vitro and in vivo.

To study the chemical constituents of Securidaca inappendiculata.The chemical constituents were isolated and purified by chromatography on silica gel, Sephadex LH-20 columns. Their structures were elucidated by means of physicochemical properties and spectroscopic analysis.Ten compounds were identified from the dichloromethane fraction of Securidaca inappendiculata, and identified as 1,7-dihydroxyxanthone (1), 1,3,8-trihydroxy-2-methoxyxanthone (2), 1,7-dihydroxy-3,4-dimethoxyxanthone (3), 1,3,8-trihydroxy-4-methoxyxanthone (4), 7-hydroxy-1,2-dimethoxyxanthone (5), 1,3,6-trihydroxy-2,7-dimethoxyxanthone (6), 1,4, 8-trihydroxyxanthone (7), 1,7-dihydroxy-3-methoxyxanthone (8), 1,6-dihydroxy-7-methoxyxanthone (9) and 1,8-dihydroxy-3,4-dimethoxyxanthone (10).Compounds 7–10 are isolated from this plant for the first time, and compounds 7–10 are isolated from this genus for the first time.

The thermodynamic properties of a nano-graphene bilayer, consisting of the upper layer A of spin-3/2 with antiferromagnetic intralayer exchange coupling and the bottom layer B of spin-5/2 with ferromagnetic intralayer exchange coupling, have been studied by the use of Monte Carlo simulation. We find a number of characteristic phenomena. The effects of the exchange coupling, the single-ion anisotropy and the longitudinal magnetic field on the internal energy, the specific heat and the blocking temperature of the mixed-spin bilayer system have been investigated in detail. The internal energy and the specific heat profiles are clarified. In particular, we have found that the specific heat curve may show two peaks phenomenon for appropriate values of the system parameters.

Using Monte Carlo simulation, we have studied the magnetic and thermal properties of a four sublattice ferromagnetic (FM) and anti-FM (AFM) double-layer superlattices system in a longitudinal magnetic field. The effects of the intralayer AFM exchange coupling $J_{{2}}$ , the single-ion anisotropy ${D}$ and the longitudinal magnetic field ${h}$ on the magnetization ${M}$ , the susceptibility ${x}$ , the internal energy ${U}$ , and the specific heat ${c}$ of the system are discussed in detail. Particular attention has been paid to the variations of the hysteresis loops of the system with the AFM exchange coupling $J_{ {2}}$ and the anisotropy ${D}$ . Some interesting results, such as the triple hysteresis and the exchange bias behavior, have been found under certain conditions.

Background Although the presences of scrapie associated fibril in the brain tissues is a ultrastructural hallmark for prion diseases, the exact morphological structure of prion during the progression of the disease is still unclear. The host prion protein (PrP) is encoded by PrP gene (PRNP) locating on the chromosome 20 in human and the chromosome 2 in mouse. Recently, a novel correlative light and electron microscopy with Mini Singlet Oxygen Generator (miniSOG) was generated. MiniSOG, a small protein of 106 amino acids, can absorb blue light and emit green fluorescence that is detectable under the fluorescence microscope. MiniSOG can also partially catalyze the polymerization of DAB to form black stained structures in the presence of osmium tetroxide, which is able to be observed under transmission electron microscope. New methods Two kinds of miniSOG-PrP expressing recombinant plasmids were generated. Correlative photooxidation and transmission electron microscope were used to detect these plasmids. The plasmids were microinjected into fertilized FVB/NJ eggs and Tg mice expressing miniSOG-PrP fusion proteins were selected after successive bred withPRNP KO Tg mice. Results Those two strains of Tg mice, TgSOG23 and Tg231SOG, developed normally and maintained healthy without detectable abnormality after one-year observation. Western blots and immunohistochemical assays with PrP- and miniSOG-specific antibodies confirmed that the chimeric miniSOG-PrP proteins were expressed in the brain tissues of Tg mice. Digital PCR assays proposed that the copy numbers of the inserted external gene in TgSOG23 and Tg231SOG were 2 and 12, respectively. Comparison with existing method(s) Compared with GFP tag miniSOG is significantly smaller, which makes it easy be operated experimentally and possibly has less influence on the biological function of the labeled protein. Additionally, GFP tag is an ideal marker for immunofluorescent assays, but may not be suitable for ultrastructural assays for prion morphology. Conclusion Those Tg mice may supply novel and useful experimental animals for further study on the potential morphological structure formation and deposits of prion in the brain tissues during prion infection.

Deep neural networks have witnessed great successes in various real applications, but it requires a large number of labeled data for training. In this paper, we propose tri-net, a deep neural network which is able to use massive unlabeled data to help learning with limited labeled data. We consider model initialization, diversity augmentation and pseudo-label editing simultaneously. In our work, we utilize output smearing to initialize modules, use fine-tuning on labeled data to augment diversity and eliminate unstable pseudo-labels to alleviate the influence of suspicious pseudo-labeled data. Experiments show that our method achieves the best performance in comparison with state-of-the-art semi-supervised deep learning methods. In particular, it achieves 8.30% error rate on CIFAR-10 by using only 4000 labeled examples.

For the bottleneck problem of the conversion efficiency in silicon-based solar cell, the Metallization Wrap– through (MWT) technology is one of the effective methods based on the analysis of factors affecting the solar cell conversion efficiency. The MWT technology is based on laser perforation and that the bus grid lines in the front surface of the solar cell are moved to the back surface. The effective area on the front surface increases and the conversion efficiency is improved. One of the most important processes in MWT technology is laser perforation and a new perforation scheme using two-dimensional laser array is designed. The high power laser is divided into a number of beams then those beams are arranged in a two-dimensional array. The silicon wafer is placed in a predetermined position by suction cup and is moved by stepper motor. The light barriers are opened by triggering switch and the silicon wafer is exposed. After a series of light, machine, and electric processes a rapid one-time two-dimensional array laser perforation on silicon wafer is formed. This patent is expected to be used in solar cell production department soon.

According to the characteristics of high altitude and strong ultraviolet radiation in Tibet, this paper do ultraviolet irradiation experiment research to different strength grades of concrete blocks in a closed laboratory, it is found that ultraviolet rays has promoting effect to early strength growth of test block, but the growth became slow along with the time.