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Background: Genome-wide association studies (GWAS) have revealed numerous loci associated with multiple sclerosis (MS). However, the challenge lies in deciphering the mechanisms by which these loci influence the target traits. Here, we employed an integrative analytical pipeline to efficiently transform genetic associations to identify novel proteins for MS. Methods: We systematically integrated MS GWAS data (N = 115,803) with human plasma proteome data (N = 7213) and conducted proteome-wide association studies (PWAS) to identify MS-associated pathogenic proteins. Following this, we employed Mendelian randomization and Bayesian colocalization analyses to verify the causal relationship between these significant plasma proteins and MS. Lastly, we utilized the Drug-Gene Interaction Database (DGIdb) to identify potential drug targets for MS. Results: The PWAS identified 25 statistically significant cis-regulated plasma proteins associated with MS at a false discovery rate of P

The object detection of natural images tends to obtain advanced semantic information through multiple convolutions and pooling, ignoring the detailed information in the feature map. Pixel-level images may be the target we are looking for in remote sensing images. This article designs a new attention mechanism that can fully utilize the spatial and channel information of the image, strengthen the region of interest, and try to protect the image's original information. Find the most influential location information in the spatial dimension and the most influential feature map in the channel dimension. Strengthen important channels and positions in the feature map to make vital information stronger and weak information not lost. Combine the designed attention mechanism with existing modules to enhance YOLO-V7 detection capability. We have merged two publicly available remote sensing image datasets, increasing object types, and richer appearance features, which can better detect model performance. Experimental results on an improved dataset have shown that the enhanced model in this article can improve the detection ability of small- and medium-sized targets in complex backgrounds, with a 1% increase in mean average precision (mAP) value and a maximum improvement of 8.2% for single-class targets. Medium targets such as airports, dams, and soccer ball fields also increase by about 5%. We also conducted experiments on the DOTA1.0 dataset to demonstrate that mAP improved by 1.1%, with 13 target categories having higher APs. The improved model reduces computational complexity by 2.7%, which is very user-friendly for embedded devices.

Abstract Contactless bubble manipulation with a high spatiotemporal resolution brings a qualitative leap forward in a variety of applications. Despite considerable advances, light-induced bubble maneuvering remains challenging in terms of robust transportation, splitting and detachment. Here, a photopyroelectric slippery surface (PESS) with a sandwich structure is constructed to achieve the versatile bubble manipulation. Due to the generated dielectric wetting and nonuniform electric field under the irradiation of near infrared (NIR) light, a bubble is subject to both the Laplace force and dielectrophoresis force, enabling a high-efficiency bubble steering. We demonstrate that the splitting, merging and detachment of underwater bubbles can be achieved with high flexibility and precision, high velocity and agile direction maneuverability. We further extend the capability of bubble control to microrobots for cargo transportation, micropart assembly and transmission of gear structures. We envision this robust bubble manipulation strategy on the PESS would provide a valuable platform for various bubble-involved processes, ranging from microfluidic devices to soft robotics.

Bipolar DC–DC converter plays an important role in data center and distributed renewable energy unit with the advantages of high efficiency and low cost. In order to improve the power density of bipolar DC–DC converter, a high frequency and high power density bipolar DC–DC converter based on Gallium Nitride High Electron Mobility Transistor (GaN HEMT) is proposed under the development trend of miniaturization, lightweight and high power density of power electronic converter. By using gallium nitride (GaN) switch device, the switching frequency of the converter is increased to 1 MHz, which effectively reduces the volume and weight of the device. In addition, through the design of high frequency driver circuit, two separate pull-up/pull-down outputs are provided for the control signal, and the rising and falling rates of the switch signal are controlled by adjusting the resistance to obtain good performance and driving stability. The experimental results show that the total weight of the converter with radiator is only 121.6 g, the power density is 35.23 W/in3, and the maximum efficiency can reach 92.7%. Compared with the same type of converter, the volume and weight of the converter are greatly reduced, effectively realizing the goals of miniaturization, lightweight and high power density of the converter.

A high-reliability SEPIC converter with reconfigurable voltage conversion gain is proposed, which is composed of a basic SEPIC converter and n extended units. Adopting an interleaved parallel structure on the input side of the converter not only achieves leg-level hardware redundancy but also reduces the input current ripple. When one branch of the converter suddenly changes or fails, due to the redundancy between branches, the converter can still to work, and the duty cycle of the other branches can be readjusted by using PI control without changing output voltage and power of the converter. This feature undoubtedly presents the reliability of the converter. On the contrary, when the converter works in normal operation, it can also actively control operation mode of each branch to achieve reconfigurable voltage conversion gain function. In addition, since the duty cycles of the switches are not limited, voltage conversion gain of the converter is widely, which makes it more suitable for the occasions where the input side fluctuates greatly. Section 2 details the working principle of the proposed converter and the voltage and current stress on components. Then, the reconfigurable voltage conversion gain of the converter and its high reliability characteristics are analyzed in Section 3. Finally, the correctness of the theoretical analysis is verified by experiments.

[This corrects the article DOI: 10.1371/journal.ppat.1006851.].

Background Avoidant paruresis is a common clinical condition in urology and psychosomatic medicine. However, it has limited treatment options that are safe and effective with few side effects.Aims Our study aimed to investigate the effectiveness and safety of the Chinese herbal Yangxin Tongquan decoction combined with cognitive–behavioural therapy (CBT) for avoidant paruresis.Methods Sixty-eight patients with avoidant paruresis were divided into a treatment group (33 patients) and a control group (35 patients). The control group was assigned 10 weeks of CBT and systematic desensitisation. In addition to CBT and systematic desensitisation, the treatment group was given the Chinese herbal Yangxin Tongquan decoction during the 10-week study. The Shy Bladder Syndrome Scale (SBS) and the Self-rating Anxiety Scale (SAS) were administered before and after treatment to measure any change.Results The overall efficacy in the treatment group (n=30) was 80.0% vs 62.5% in the control group (n=33). Comparing pretreatment and post-treatment measures, both groups showed improvement in SBS scores and SAS scores (treatment group: t(SBS)=8.397, p(SBS)

This study investigates the impact of capitalizing educational resources on housing prices. As housing has gradually transitioned from a basic social right to a means of accumulating individual and familial wealth, it has emerged as a significant indicator of social stratification and has increasingly become a crucial tool for the intergenerational reproduction of social class. This paper takes Nanjing, China, as a case study and uses the geographically weighted regression model (GWR) and the hedonic pricing model (HPM) to investigate the impact of high-quality primary schools on housing prices. The results show that high-quality educational resources have become the most significant influencing factor on residential prices in Nanjing. The analysis in the mechanism section further indicates that the uneven distribution of educational resources in China is a continuation of the “danwei” system. Moreover, during the urbanization process, these high-quality educational resources are often leveraged by the government and developers, who see them as essential tools to attract investment and inflate housing prices. Therefore, the current overlap of the school district system and the marketization of housing in China not only intensifies residential segregation within the city, leading to severe residential inequality but also rebuilds social segregation within “danwei” and facilitates its reproduction.

With Agriophyllum sargassum powder, mixed grain powder, mixed beans powder and filling powder as the main raw material, the D-optimal mixture design was used to study the effect of different mix proportion on the comprehensive score of simulated Agriophyllum sargassum compound meal replacement powder, the regression model was established between comprehensive score with distribution proportion, the interaction effect of each raw material in the formulations was researched, the optimal formulations of Agriophyllum sargassum compound meal replacement powder was determined as follows: Agriophyllum sargassum powder 22%, mixed grain powder 39%, mixed beans powder 35% and filling powder 4%. Under this formula condition, the protein nutrition value analysis of meal replacement powder showed that the SRCAA and EAAI values of meal replacement powder were 82.02 and 63.14, respectively, indicating that the protein nutrition of meal replacement powder was better. Combined with BV, NI, SRCAA and EAAI indexes, the nutritional value of meal replacement meal protein was comprehensively evaluated. The results showed that the Agriophyllum sargassum compound meal replacement powder had higher nutritional value.

Background: The effect of laparoscopic sleeve gastrectomy (LSG) in the treatment of type 2 diabetes (T2D) patients with body mass index (BMI is calculated by dividing weight in kilograms by height in meters squared) higher than 25 kg/m2 but lower than 32.5 kg/m2, especially in East Asian population characterized by abdominal obesity, are still unclear. This study aims to explore the effect of LSG in T2D patients with BMI higher than 25 kg/m2 but lower than 32.5 kg/m2. Methods: A total of 49 T2D patients with BMI(25–32.5 kg/m2) treated successfully with LSG were included in our study. The effect of LSG on T2D remission outcomes at 12 and 24 months after operation was analyzed. Results: All patients were treated successfully with LSG without conversion. The mean preoperative body weight,BMI, fasting plasma glucose, glycosylated hemoglobin (A1c) and fasting C-peptide were 81.7 ± 10.0 kg, 29.1 ± 2.4 kg/m2, 10.4 ± 3.9 mmol/L,8.2 ± 1.5%, and 2.3 ± 1.1 nmol/L,respectively.The age, duration of diabetes and ABCD score were 48.6 ± 9.6 years,6.6 ± 5.1 years, and 2.9 ± 1.5. The mean fasting plasma glucose,A1c, and C-peptide levels were significantly decreased at 12 and 24 months after operation. At postoperative 24 months, 18 out of 49 patients (36.7%) reached diabetes complete remission (A1c levels≤6.0%).14 out of 49 patients (28.6%) reached partial remission (6.0%

Abstract Conventional vision-based systems, such as cameras, have demonstrated their enormous versatility in sensing human activities and developing interactive environments. However, these systems have long been criticized for incurring privacy, power, and latency issues due to their underlying structure of pixel-wise analog signal acquisition, computation, and communication. In this research, we overcome these limitations by introducing in-sensor analog computation through the distribution of interconnected photodetectors in space, having a weighted responsivity, to create what we call a computational photodetector. Computational photodetectors can be used to extract mid-level vision features as a single continuous analog signal measured via a two-pin connection. We develop computational photodetectors using thin and flexible low-noise organic photodiode arrays coupled with a self-powered wireless system to demonstrate a set of designs that capture position, orientation, direction, speed, and identification information, in a range of applications from explicit interactions on everyday surfaces to implicit activity detection.

Grape gray mold disease (Botrytis cinerea) is widespread during grape production especially in Vitis vinifera and causes enormous losses to the grape industry. In nature, the grapevine cultivar ‘Beta ‘ (Vitis riparia × Vitis labrusca) showed high resistance to grape gray mold. Until now, the candidate genes and their mechanism of gray mold resistance were poorly understood. In this study, we firstly conducted quantitative trait locus (QTL) mapping for grape gray mold resistance based on two hybrid offspring populations that showed wide separation in gray mold resistance. Notably, two stable QTL related to gray mold resistance were detected and located on linkage groups LG2 and LG7. The phenotypic variance ranged from 6.86% to 13.70% on LG2 and 4.40% to 11.40% on LG7. Combined with RNA sequencing (RNA-seq), one structural gene VlEDR2 (Vitvi02g00982) and three transcription factors VlERF039 (Vitvi00g00859), VlNAC047 (Vitvi08g01843), and VlWRKY51 (Vitvi07g01847) that may be involved in VlEDR2 expression and grape gray mold resistance were selected. This discovery of candidate gray mold resistance genes will provide an important theoretical reference for grape gray mold resistance mechanisms, research, and gray mold-resistant grape cultivar breeding in the future.

ObjectivePain empathy’s preferential nature tends to trigger prejudice and intergroup conflicts. Given the current degree of proliferation of doctor–patient conflict news in China, this study aims to determine whether readers of doctor–patient news-initiated moral judgments prefer pain empathy for doctors or patients.Materials and methodsThis study utilized localized doctor–patient news with high or low moral performance (based on morality ratings of patients’ behaviors) as moral-judgment-eliciting materials, and painful pictures as pain empathy-eliciting materials. The event-related potential (ERP) technique was utilized to assess moral judgment’s effect on the cognitive empathy component and to investigate electroencephalogram signals’ accuracy in classifying four brain response patterns when facing doctor or patient is experiencing or not experiencing pain.ResultsUnder low moral text material, participants exhibited smaller mean wave amplitude of positive 300 (P3) and late positive potential (LPP) to painful pictures than non-painful pictures when facing patients; under high moral text material, participants exhibited larger mean wave amplitude of P3 and LPP to painful pictures than non-painful pictures when facing doctors. Electroencephalogram (EEG) signals’ classification accuracy was significant in 0–1,000 ms in both high and low moral judgments, but the classification accuracy was higher in low moral judgments in some cognitive empathy stages (0.51, 0.53–0.55, 0.66–0.79, and 0.88–1 s).ConclusionUnder low moral judgment, individuals pay less attention to the patient’s (perpetrator’s) pain; under high moral judgment, individuals empathize with the doctor (the person praised), showing that news-induced moral judgment can sway readers’ empathy for different social groups. In cognitive empathy, individuals’ brain representations are more discriminatory under low than high moral judgments when confronted with pain by doctors and patients, which provides insight into objectively recognizing group bias.

ABSTRACT: In November 2021, a 19-year-old medical student was diagnosed with a rabbit-derived Thelazia callipaeda infection in her left eye. She visited her doctor because she removed the white object by herself with a cotton swab 2 days earlier. She explained to the doctor that she rubbed her eyes without washing her hands when rabbit hair got into her eyes during the animal experiment class at school 2 weeks earlier. The other 2 worms were then taken out with ophthalmic forceps and were placed into physiological saline. The worms were sent to the Shandong Academy of Eye Disease Prevention and Therapy for examination. After identification, the worms were regarded as the female T. callipaeda. Ofloxacin eye drops and peranapulin eye drops were administered to control inflammation. No abnormality was found in the follow-up 2 weeks and 1 month later. This report highlights that it is very important to strengthen the health and safety education of medical students during animal experiment classes.

Host defense systems employ posttranslational modifications to protect against invading pathogens. Here, we found that protein inhibitor of activated STAT 1 (PIAS1) interacts with the nucleoprotein (NP), polymerase basic protein 1 (PB1), and polymerase basic protein 2 (PB2) of influenza A virus (IAV). Lentiviral-mediated stable overexpression of PIAS1 dramatically suppressed the replication of IAV, whereas siRNA knockdown or CRISPR/Cas9 knockout of PIAS1 expression significantly increased virus growth. The expression of PIAS1 was significantly induced upon IAV infection in both cell culture and mice, and PIAS1 was involved in the overall increase in cellular SUMOylation induced by IAV infection. We found that PIAS1 inhibited the activity of the viral RNP complex, whereas the C351S or W372A mutant of PIAS1, which lacks the SUMO E3 ligase activity, lost the ability to suppress the activity of the viral RNP complex. Notably, the SUMO E3 ligase activity of PIAS1 catalyzed robust SUMOylation of PB2, but had no role in PB1 SUMOylation and a minimal role in NP SUMOylation. Moreover, PIAS1-mediated SUMOylation remarkably reduced the stability of IAV PB2. When tested in vivo, we found that the downregulation of Pias1 expression in mice enhanced the growth and virulence of IAV. Together, our findings define PIAS1 as a restriction factor for the replication and pathogenesis of IAV.

Morchella spp. are well-known and economically valuable edible mushrooms. The molecular mechanism of development in Morchella fungi is poorly understood, although it can be artificially cultivated. In this paper, the intracellular proteomes of three vegetative growth stages (mycelial, sclerotial initiation and maturation) and two sexual reproductive growth stages (young and mature ascocarp) of M. importuna were analyzed by LC-MS/MS. A total of 2060 credible proteins were identified. Label-free quantitative analysis showed that, consistent with physiological development, the number of differentially expressed proteins increased, which were mainly enriched in carbohydrate and amino acid metabolic pathways by GO and KAAS enrichment analysis. Besides, the categories for upregulated proteins enriched in were more in sexual reproduction stage, especially in the young ascocarp stage, than those in the vegetative growth stage, including aminoacyl-tRNA biosynthesis, histidine, peroxisome, beta-alanine metabolism, etc. In addition, the expression pattern of individual protein (top-20) suggested that the most abundant lectin protein (8.92%) played an important role in the development of M. importuna. This study comprehensively analyzed the whole developmental process of M. importuna at the proteome level, which may help us to better understand its nutrition metabolism and fruiting body development.

Agrocybe cylindracea, an edible mushroom, is widely cultivated for its abundance of nutrients and flavor, and many of its metabolites are reported to have beneficial roles, such as medicinal effects on tumors and chronical illnesses. However, the lack of genomic information has hindered further molecular studies on this fungus. Here, we present a genome assembly of A. cylindracea together with comparative genomics and pathway analyses of Agaricales species. The draft, generated from both next-generation sequencing (NGS) and single-molecule real-time (SMRT) sequencing platforms to overcome high genetic heterozygosity, is composed of a 56.5 Mb sequence and 15,384 predicted genes. This mushroom possesses a complex reproductive system, including tetrapolar heterothallic and secondary homothallic mechanisms, and harbors several hydrolases and peptidases for gradual and effective degradation of various carbon sources. Our pathway analysis reveals complex processes involved in the biosynthesis of polysaccharides and other active substances, including B vitamins, unsaturated fatty acids, and N-acetylglucosamine. RNA-seq data show that A. cylindracea stipes tend to synthesize carbohydrate for carbon sequestration and energy storage, whereas pilei are more active in carbon utilization and unsaturated fatty acid biosynthesis. These results reflect diverse functions of the two anatomical structures of the fruiting body. Our comprehensive genomic and transcriptomic data, as well as preliminary comparative analyses, provide insights into the molecular details of the medicinal effects in terms of active compounds and nutrient components.

Abstract Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.

The active asteroid 311P/PanSTARRS is one of the two targets of the planned Chinese asteroid exploration mission Tianwen-2. During 2013, 311P experienced several mass-loss events and exhibited multiple comet-like tails. Here we analyze the morphology and surface brightness of the tails to investigate the dust environment around the nucleus and the mechanism of activities. We enhance the features of the tails using image processing techniques to obtain information about the morphologies of the tails, and fit the processed images with syndyne–synchrone diagrams. The fitting results give estimations of the upper limits of the durations (2–8 days) of eruptions and the dust size ranges (0.006 –38.9 mm) in the tails. The results of surface photometry performed for each dust tail show that the brightness distribution index of each tail ranged from approximately −1.81 to 0 and the dust size distribution indices of 311P's tails ranged from −2.29 to −1.45. The quantity of particles in each tail ranged from 0.5 to 8 × 10 ^6 kg, which leads to a total dust-loss quantity of 3.0 × 10 ^7 kg and a mass-loss rate of 1.59 kg s ^−1 . Sublimation, continuous impacts, or tidal forces of planets are excluded as explanations for 311P’s activities, and rotational instability remains a possible activation cause without strong evidence against it.

Abstract Background White rot is one of the most dangerous fungal diseases and can considerably affect grape berry production and quality. However, few studies have focused on this disease, and thus, finding candidate white rot resistance genes is of great importance for breeding resistant grapevine cultivars. Based on field observations and indoor experiments, the cultivars “Victoria” and “Zhuosexiang” showed significant differences in white rot resistance. For understanding the molecular mechanisms behind it, different phenotypes of grapevine leaves were used for RNA sequencing via Illumina and single-molecule real-time (SMRT) sequencing technology. Results A transcript library containing 53,906 reads, including known and novel transcripts, was constructed following the full-length transcriptome sequencing of the two grapevine cultivars. Genes involved in salicylic acid (SA) and jasmonic acid (JA) synthesis pathways showed different expression levels. Furthermore, four key transcription factors (TFs), NPR1, TGA4, Pti6, and MYC2, all involved in the SA and JA signal pathways were identified, and the expression profile revealed the different regulation of the pathogenesis related protein1 (PR1) resistance gene, as mediated by the four TFs. Conclusions Full-length transcript sequencing can substantially improve the accuracy and integrity of gene prediction and gene function research in grapevine. Our results contribute to identify candidate resistance genes and improve our understanding of the genes and regulatory mechanisms involved in grapevine resistance to white rot.

The onsite next generation sequencing (NGS) of Ebola virus (EBOV) genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin, transmission, and evolution of this virus. Herein, we have diagnosed a cohort of EBOV patients in Sierra Leone in 2015, during the late phase of the outbreak. The surviving EBOV patients had a recovery process characterized by decreasing viremia, fever, and biochemical parameters. EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection, including the previously described short stretches of 13 serial T>C mutations. Remarkably, within individual patients, samples collected during the early phase of infection possessed Ts at these nucleotide sites, whereas they were replaced by Cs in samples collected in the later phase, suggesting that these short stretches of T>C mutations could emerge independently. In addition, up to a total of 35 nucleotide sites spanning the EBOV genome were mutated coincidently. Our study showed the dynamic intra-host adaptation of EBOV during patient recovery and gave more insight into the complex EBOV-host interactions.

This paper explores whether a Student’s choice of major leads to certain personality traits and the reasons for this phenomenon. Specifically, we look at evidence from two Chinese universities, both of which specialize in agricultural studies. Using the Sixteen Personality Factor (16PF) questionnaire and the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI) questionnaire, we collected data from two groups of students: those who study agriculture-related majors (ARM), and those who study non-agriculture-related majors (NARM). The surveys all showed no significant change in personality traits during Students’ freshman year. However, after 3 years of university study, significant personality trait changes were noted between seniors in the ARM and NARM groups. Whereas ARM seniors tended to be socially shy and lower in communicative competence, NARM seniors were better at expressing themselves and communicating with others. Although a Student’s choice of profession has an influence on their personality traits, it is not the only factor. The differences between ARM and NARM training models and curricula are also undoubtedly significant. Moreover, the bias against ARM in Chinese society further magnifies the differences in personality traits among students with different majors.

In this study, the martensitic stainless-steel powder had been successfully deposited on the surfaces of 1045 wrought steel substrates using five types of laser metal deposition strategies. The results showed that a thin buffer layer can be naturally generated in-between the deposition layer and substrate owning to the dilution effect, producing functionally graded structures consisted of martensite dendrite matrices and intermetallic phases (e.g., M23(C, B)6). Unfortunately, the poor deformation characteristic of natural buffer layers can exacerbate the risk of cracking, leading to an incompatibility between martensitic stainless steel and forming steel. A thick artificial buffer layer was then designed by addition of Inconel 625 powder. Because of the formation of graded austenite phase in the artificial buffer layer, the yield strength of specimen was enhanced significantly. Hence, our study can be used for manufacture of reliable moulds with high surface hardness and structural strength and may be helpful in further developing hybrid forming strategy in the field of mould manufacture. When subjected to stress impact during mould filling, the artificial buffer layer with functionally graded properties would have a perfect capability to bear the deformation as the load increased, dramatically improving the reliability and functionality of moulds.

Posttranslational modifications, such as SUMOylation, play specific roles in the life cycle of invading pathogens. However, the effect of SUMOylation on the adaptation, pathogenesis, and transmission of influenza A virus (IAV) remains largely unknown. Here, we found that a conserved lysine residue at position 612 (K612) of the polymerase basic protein 1 (PB1) of IAV is a bona fide SUMOylation site. SUMOylation of PB1 at K612 had no effect on the stability or cellular localization of PB1, but was critical for viral ribonucleoprotein (vRNP) complex activity and virus replication in vitro. When tested in vivo, we found that the virulence of SUMOylation-defective PB1/K612R mutant IAVs was highly attenuated in mice. Moreover, the airborne transmission of a 2009 pandemic H1N1 PB1/K612R mutant virus was impaired in ferrets, resulting in reversion to wild-type PB1 K612. Mechanistically, SUMOylation at K612 was essential for PB1 to act as the enzymatic core of the viral polymerase by preserving its ability to bind viral RNA. Our study reveals an essential role for PB1 K612 SUMOylation in the pathogenesis and transmission of IAVs, which can be targeted for the design of anti-influenza therapies.

Few reports exist on QTL mapping of the important economic traits of hawthorn. We hybridized the cultivars 'Shandongdamianqiu' (female parent) and 'Xinbinruanzi' (male parent), and 130 F1 individuals and the two parents were used for RAD-seq, SNP development, and high-density linkage map construction. Three genetic maps were obtained, one for each of the parents and an integrated one. In these three maps, 17 linkage groups were constructed. The female and male parent maps contained 2657 and 4088 SNP markers, respectively, and had genetic distances of 2689.65 and 2558.41 cM, respectively, whereas the integrated map was 2470.02 cM, and contained 6,384 SNP markers. QTL mapping based on six agronomic traits, namely fruit transverse diameter, vertical diameter, single fruit weight, pericarp brittleness, pericarp puncture hardness, and average sarcocarp firmness were conducted, and 25 QTLs were detected in seven linkage groups. Explained phenotypic variation rate ranged from 17.7% to 35%. This genetic map contains the largest number of molecular markers ever obtained from hawthorn and will provide an important future reference for fine QTL mapping of economic traits and molecular assisted selection of hawthorn.

The climatology of the mesoscale eddies in the upper layer of the South China Sea (SCS) is investigated for an understanding of its genesis using the outputs from a 1/12.5° ocean reanalysis. Employed is a recently developed multiscale energetics formalism on the basis of a multiscale window transform (MWT) and the theory of canonical transfer. Three scale windows, namely, background flow, mesoscale eddy and synoptic eddy, are differentiated, and fields on different scales are reconstructed henceforth. Diagnosis of the mesoscale eddy energy budget reveals that barotropic and baroclinic instabilities, wind work, advection and pressure work are essential ingredients of the eddy energy sources and sinks in the SCS, but their contributions vary from region to region. In the southwestern part of the SCS, the regional mesoscale eddy energy is mainly generated by barotropic instability, while in the northeastern SCS, baroclinic instability and the wind working directly on the eddies are the two dominant eddy generation processes. The eddies southwest of Taiwan are damped by outward energy transport via advection, while the decay of those southeast of Vietnam is due to pressure work. The three-scale framework also reveals that the interaction between the mesoscale eddies and higher-frequency synoptic eddies mainly serves as a sink for the mesoscale eddy energy in the SCS, except for the northeastern SCS, where significant inverse cascade of kinetic energy is found.

Abstract Background Data on the association between socioeconomic status and post-stroke functional outcome in developing countries is lacking. We aimed to evaluate the association in stroke survivors in deprived rural Southern China. Methods We conducted door-to-door interviews and collected data using a structured questionnaire in stroke survivors from five fourth-class rural areas of Guangdong Province through a non-government initiated registry from August 2014 to March 2015. Descriptive statistics were used to provide information on the demographic, socioeconomic and clinical characteristics of the selected population. Univariate and multivariate logistic regression were used to examine the relationship of socioeconomic status indexed by self-reported average family income and functional impairment defined as a modified Rankin Scale of 3 to 5. Results Among the 425 stroke survivors, 52.7% lived below the poverty line set by the local government. About 50% of patients suffered from functional impairment and required assistance in their daily life. Compared with their wealthier counterpart, stroke survivors with lower income were more likely to have functional impairment (OR 2.85, 95% CI 1.93—4.23). The effect size increased and remained significant after adjusting for possible confounding factors (OR 3.17, 95% CI 2.04—4.91). Conclusions Poorer patients tend to have poorer post-stroke functional outcome. Primary and secondary strategies targeting underprivileged populations in less-developed areas are thus urgently needed in China.

Abstract Background Non-structural protein 1 (NS1) is a multifunctional protein and a crucial regulatory factor in the replication and pathogenesis of avian influenza virus (AIV). Studies have shown that NS1 can interact with a variety of host proteins to modulate the viral life cycle. We previously generated a monoclonal antibody against NS1 protein; In the current research study, using this antibody, we immunoprecipitated host proteins that interact with NS1 to better understand the roles played by NS1 in communications between virus and host. Results Co-immunoprecipitation experiments identified annexin A2 (ANXA2) as a target molecule interacting with NS1. Results from confocal laser scanning microscopy indicated that NS1 co-localized with ANXA2 in the cell cytoplasm. Overexpression of ANXA2 significantly increased the titer of H5N1 subtype HPAIV, whereas siRNA-mediated knockdown of ANXA2 markedly inhibited the expression of viral proteins and reduced the progeny virus titer. Conclusions Our results indicate that ANXA2 interacts with NS1 and ANXA2 expression increases HPAIV replication.

Abstract Genetic linkage maps are an important tool in genetic and genomic research. In this study, two hawthorn cultivars, Qiujinxing and Damianqiu, and 107 progenies from a cross between them were used for constructing a high-density genetic linkage map using the 2b-restriction site-associated DNA (2b-RAD) sequencing method, as well as for mapping quantitative trait loci (QTL) for flavonoid content. In total, 206,411,693 single-end reads were obtained, with an average sequencing depth of 57× in the parents and 23× in the progeny. After quality trimming, 117,896 high-quality 2b-RAD tags were retained, of which 42,279 were polymorphic; of these, 12,951 markers were used for constructing the genetic linkage map. The map contained 17 linkage groups and 3,894 markers, with a total map length of 1,551.97 cM and an average marker interval of 0.40 cM. QTL mapping identified 21 QTLs associated with flavonoid content in 10 linkage groups, which explained 16.30–59.00% of the variance. This is the first high-density linkage map for hawthorn, which will serve as a basis for fine-scale QTL mapping and marker-assisted selection of important traits in hawthorn germplasm and will facilitate chromosome assignment for hawthorn whole-genome assemblies in the future.

ABSTRACT Avian influenza viruses (AIVs) must acquire mammalian-adaptive mutations before they can efficiently replicate in and transmit among humans. The PB2 E627K mutation is known to play a prominent role in the mammalian adaptation of AIVs. The H7N9 AIVs that emerged in 2013 in China easily acquired the PB2 E627K mutation upon replication in humans. Here, we generate a series of reassortant or mutant H7N9 AIVs and test them in mice. We show that the low polymerase activity attributed to the viral PA protein is the intrinsic driving force behind the emergence of PB2 E627K during H7N9 AIV replication in mice. Four residues in the N-terminal region of PA are critical in mediating the PB2 E627K acquisition. Notably, due to the identity of viral PA protein, the polymerase activity and growth of H7N9 AIV are highly sensitive to changes in expression levels of human ANP32A protein. Furthermore, the impaired viral polymerase activity of H7N9 AIV caused by the depletion of ANP32A led to reduced virus replication in Anp32a−/− mice, abolishing the acquisition of the PB2 E627K mutation and instead driving the virus to acquire the alternative PB2 D701N mutation. Taken together, our findings show that the emergence of the PB2 E627K mutation of H7N9 AIV is driven by the intrinsic low polymerase activity conferred by the viral PA protein, which also involves the engagement of mammalian ANP32A. IMPORTANCE The emergence of the PB2 E627K substitution is critical in the mammalian adaptation and pathogenesis of AIV. H7N9 AIVs that emerged in 2013 possess a prominent ability in gaining the PB2 E627K mutation in humans. Here, we demonstrate that the acquisition of the H7N9 PB2 E627K mutation is driven by the low polymerase activity conferred by the viral PA protein in human cells, and four PA residues are collectively involved in this process. Notably, the H7N9 PA protein leads to significant dependence of viral polymerase function on human ANP32A protein, and Anp32a knockout abolishes PB2 E627K acquisition in mice. These findings reveal that viral PA and host ANP32A are crucial for the emergence of PB2 E627K during adaptation of H7N9 AIVs to humans.

The present study describes a two-step synthesis process for the cobalt complex of tetra-2,3-(5,6-di-tert-butyl-pyrazino) porphyrazine (tBu-TPyzPzCo). The product was ultrasonically impregnated onto carbon black (CB) to prepare a supported catalyst (tBu-TPyzPzCo/CB). We built a split photoelectric catalytic device to test the performance of photocatalytic, electrocatalytic and photoelectrocatalytic degradation of partially hydrolyzed polyacrylamide (HPAM). The results confirm that HPAM exhibited more efficient degradation in the presence of a supporting catalyst using the photoelectrocatalytic process than by photocatalytic or electrocatalytic oxidation—or even the sum of the two in saline water. The photoelectrocatalytic reaction confirmed that the process conforms to quasi-first order reaction kinetics, while the reaction rate constants were 6.03 times that of photocatalysis and 3.97 times that of electrocatalysis. We also compared the energy consumption of the three processes and found that the photoelectrocatalytic process has the highest energy efficiency.

Metal nanoclusters (NCs), including Au, Ag, Cu, Pt, Ni and alloy NCs, have become more and more popular sensor probes with good solubility, biocompatibility, size-dependent luminescence and catalysis. The development of electrochemiluminescent (ECL) and chemiluminescent (CL) analytical methods based on various metal NCs have become research hotspots. To improve ECL and CL performances, many strategies are proposed, from metal core to ligand, from intermolecular electron transfer to intramolecular electron transfer. Combined with a variety of amplification technology, i.e., nanostructure-based enhancement and biological signal amplification, highly sensitive ECL and CL analytical methods are developed. We have summarized the research progresses since 2016. Also, we discuss the current challenges and perspectives on the development of this area.

The combination of additive manufacturing and conventional metal forming processes provides the possibility for improvements of forming efficiency and flexibility. Substrate preheating is an implementable technique to improve the interface adhesion properties of the hybrid forming method. The present experiment investigates the adhesion of additive manufactured 316 L steel on P20 and 1045 steel substrates under two substrate temperatures, and the geometrical characterization, interfacial microstructure and mechanical property of the hybrid specimens were compared. As a result, it was found that the ratio of deposition height to the width was reduced and the width was increased under substrate preheating. Tensile results show that the ultimate strength of 1045 and 316 L hybrid specimens was obviously increased, while the properties of hybrid specimens P20 and 316 L were similar, under different substrate temperature conditions. For the hybrid specimens with the metallurgically bonding characteristic, the tensile properties can reach the level of 316 L depositioned specimens fabricated by laser metal deposition (LMD). Furthermore, substrate preheating had little effect on the microstructure of the laser metal deposition zone, and significant influence on the microstructure of the heat affected zone, which was reflected in the difference of the hardness distribution.

Accurate detection of locations of indoor high-density crowds is crucial for early warning and emergency rescue during indoor safety accidents. The spatial structure of indoor environments is more complicated than outdoor environments. The locations of indoor high-density crowds are more likely to be the sites of security accidents. Existing detection methods for high-density crowd locations mostly focus on outdoor environments, and relatively few detection methods exist for indoor environments. This study proposes a novel detection framework for high-density indoor crowd locations termed IndoorSRC (Simplification–Reconstruction–Cluster). In this paper, a novel indoor spatiotemporal clustering algorithm called Indoor-STAGNES is proposed to detect the indoor trajectory stay points to simplify indoor movement trajectory. Then, we propose use of a Kalman filter algorithm to reconstruct the indoor trajectory and properly align and resample the data. Finally, an indoor spatiotemporal density clustering algorithm called Indoor-STOPTICS is proposed to detect the locations of high-density crowds in the indoor environment from the reconstructed trajectory. Extensive experiments were conducted using indoor Wi-Fi positioning datasets collected from a shopping mall. The results show that the IndoorSRC framework evidently outperforms the existing baseline method in terms of detection performance.

Transcription and replication of the influenza A virus (IAV) genome occur in the nucleus of infected cells and are carried out by the viral ribonucleoprotein complex (vRNP). As a major component of the vRNP complex, the viral nucleoprotein (NP) mediates the nuclear import of the vRNP complex via its nuclear localization signals (NLSs). Clearly, an effective way for the host to antagonize IAV infection would be by targeting vRNP nuclear import. Here, we identified phospholipid scramblase 1 (PLSCR1) as a binding partner of NP by using a yeast two-hybrid (Y2H) screen. The interaction between NP and PLSCR1 in mammalian cells was demonstrated by using co-immunoprecipitation and pull-down assays. We found that the stable overexpression of PLSCR1 suppressed the nuclear import of NP, hindered the virus life cycle, and significantly inhibited the replication of various influenza subtypes. In contrast, siRNA knockdown or CRISPR/Cas9 knockout of PLSCR1 increased virus propagation. Further analysis indicated that the inhibitory effect of PLSCR1 on the nuclear import of NP was not caused by affecting the phosphorylation status of NP or by stimulating the interferon (IFN) pathways. Instead, PLSCR1 was found to form a trimeric complex with NP and members of the importin α family, which inhibited the incorporation of importin β, a key mediator of the classical nuclear import pathway, into the complex, thus impairing the nuclear import of NP and suppressing virus replication. Our results demonstrate that PLSCR1 negatively regulates virus replication by interacting with NP in the cytoplasm and preventing its nuclear import.

Genetic maps are important tools in plant genomics and breeding. We report a large-scale discovery of single nucleotide polymorphisms (SNPs) using the specific length amplified fragment sequencing (SLAF-seq) technique for the construction of high-density genetic maps for two elite wine grape cultivars, 'Chardonnay' and 'Beibinghong', and their 130 F1 plants. A total of 372.53 M paired-end reads were obtained after preprocessing. The average sequencing depth was 33.81 for 'Chardonnay' (the female parent), 48.20 for 'Beibinghong' (the male parent), and 12.66 for the F1 offspring. We detected 202,349 high-quality SLAFs of which 144,972 were polymorphic; 10,042 SNPs were used to construct a genetic map that spanned 1,969.95 cM, with an average genetic distance of 0.23 cM between adjacent markers. This genetic map contains the largest molecular marker number of the grape maps so far reported. We thus demonstrate that SLAF-seq is a promising strategy for the construction of high-density genetic maps; the map that we report here is a good potential resource for QTL mapping of genes linked to major economic and agronomic traits, map-based cloning, and marker-assisted selection of grape.

To clarify the relationship between neutral lipid content and cordycepin accumulation in Cordyceps militaris, mutants were generated from mixed spores of two C. militaris strains with varying cordycepin-producing capacities. Fifteen stable mutants producing from 0.001 to 2.363 mg/mL cordycepin were finally selected. The relative fluorescence intensities of the 15 mutants, two C. militaris strains and an Aspergillus nidulans strain at different concentrations of lyophilized mycelium powder were then investigated using the Nile red method. The mutant CM1-1-1 with the highest relative fluorescence intensity among the eighteen strains was selected for optimizing the Nile red method. Relative fluorescence intensity was linearly correlated with cordycepin concentration in liquid broth (R2 = 0.9514) and in lyophilized mycelium powder (R2 = 0.9378) for the 18 cordycepin-producing strains under identical culture conditions and with cordycepin concentration in liquid broth (R2 = 0.9727) and in lyophilized mycelium powder (R2 = 0.9613) for CM1-1-1 under eight different sets of conditions. In addition, the cordycepin content in lyophilized mycelium powder measured by the Nile red method was linearly correlated with that determined by an HPLC method (R2 = 0.9627). In conclusion, neutral lipids in lipid droplets are required during cordycepin accumulation; these neutral lipids are potential biomarkers of cordycepin biosynthesis.

Calibration transfer is an important field for near-infrared (NIR) spectroscopy in practical applications. However, most transfer methods are constructed with standard samples, which are expensive and difficult to obtain. Taking this problem into account, this paper proposes a calibration transfer method based on affine invariance without transfer standards (CTAI). Our method can be utilized to adjust the difference between two instruments by affine transformation. CTAI firstly establishes a partial least squares (PLS) model of the master instrument to obtain score matrices and predicted values of the two instruments, and then the regression coefficients between each of the score vectors and predicted values are computed for the master instrument and the slave instrument, respectively. Next, angles and biases are calculated between the regression coefficients of the master instrument and the corresponding regression coefficients of the slave instrument, respectively. Finally, by introducing affine transformation, new samples are predicted based on the obtained angles and biases. A comparative study between CTAI and the other five methods was conducted, and the performances of these algorithms were tested with two NIR spectral datasets. The obtained experimental results show clearly that, in general CTAI is more robust and can also achieve the best Root Mean Square Error of test sets (RMSEPs). In addition, the results of statistical difference with the Wilcoxon signed rank test show that CTAI is generally better than the others, and at least statistically the same.

In order to enable the calibration model to be effectively transferred among multiple instruments and correct the differences between the spectra measured by different instruments, a new feature transfer model based on partial least squares regression (PLS) subspace (PLSCT) is proposed in this paper. Firstly, the PLS model of the master instrument is built, meanwhile a PLS subspace is constructed by the feature vectors. Then the master spectra and the slave spectra are projected into the PLS subspace, and the features of the spectra are also extracted at the same time. In the subspace, the pseudo predicted feature of the slave spectra is transferred by the ordinary least squares method so that it matches the predicted feature of the master spectra. Finally, a feature transfer relationship model is constructed through the feature transfer of the PLS subspace. This PLS-based subspace transfer provides an efficient method for performing calibration transfer with only a small number of standard samples. The performance of the PLSCT was compared and assessed with slope and bias correction (SBC), piecewise direct standardization (PDS), calibration transfer method based on canonical correlation analysis (CCACT), generalized least squares (GLSW), multiplicative signal correction (MSC) methods in three real datasets, statistically tested by the Wilcoxon signed rank test. The obtained experimental results indicate that PLSCT method based on the PLS subspace is more stable and can acquire more accurate prediction results.

Softening, a common phenomenon in many fruits, is a well coordinated and genetically determined process. However, the process of flesh softening during ripening has rarely been described in hawthorn. In this study, we found that ‘Ruanrou Shanlihong 3 Hao’ fruits became softer during ripening, whereas ‘Qiu JinXing’ fruits remained hard. At late developmental stages, the firmness of ‘Ruanrou Shanlihong 3 Hao’ fruits rapidly declined, and that of ‘Qiu JinXing’ fruits remained essentially unchanged. According to transmission electron microscopy (TEM), the middle lamella of ‘Qiu JinXing’ and ‘Ruanrou Shanlihong 3 Hao’ fruit flesh was largely degraded as the fruits matured. Microfilaments in ‘Qiu JinXing’ flesh were arranged close together and were deep in color, whereas those in ‘Ruanrou Shanlihong 3 Hao’ fruit flesh were arranged loosely, partially degraded and light in color. RNA-Seq analysis yielded approximately 46.72 Gb of clean data and 72,837 unigenes. Galactose metabolism and pentose and glucuronate interconversions are involved in cell wall metabolism, play an important role in hawthorn texture. We identified 85 unigenes related to the cell wall between hard- and soft-fleshed hawthorn fruits. Based on data analysis and real-time PCR, we suggest that β-GAL and PE4 have important functions in early fruit softening. The genes Ffase, Gns, α-GAL, PE63, XTH and CWP, which are involved in cell wall degradation, are responsible for the different textures of hawthorn fruits. Thus, we hypothesize that the different textures of ‘Qiu JinXing’ and ‘Ruanrou Shanlihong 3 Hao’ fruits at maturity mainly result from cellulose/hemicelluloses degradation rather than from lamella degradation. Overall, we propose that different types of hydrolytic enzymes in cells interact to degrade the cell wall, resulting in ultramicroscopic Structure changes in the cell wall and, consequently, fruit softening. These results provide fundamental insight regarding the mechanisms by which hawthorn fruits acquire different textures and also lay a solid foundation for further research.

Coconut (Cocos nucifera L.), a member of the palm family (Arecaceae), is one of the most economically important crops in tropics, serving as an important source of food, drink, fuel, medicine, and construction material. Here we report an assembly of the coconut (C. nucifera, Oman local Tall cultivar) mitochondrial (mt) genome based on next-generation sequencing data. This genome, 678,653bp in length and 45.5% in GC content, encodes 72 proteins, 9 pseudogenes, 23 tRNAs, and 3 ribosomal RNAs. Within the assembly, we find that the chloroplast (cp) derived regions account for 5.07% of the total assembly length, including 13 proteins, 2 pseudogenes, and 11 tRNAs. The mt genome has a relatively large fraction of repeat content (17.26%), including both forward (tandem) and inverted (palindromic) repeats. Sequence variation analysis shows that the Ti/Tv ratio of the mt genome is lower as compared to that of the nuclear genome and neutral expectation. By combining public RNA-Seq data for coconut, we identify 734 RNA editing sites supported by at least two datasets. In summary, our data provides the second complete mt genome sequence in the family Arecaceae, essential for further investigations on mitochondrial biology of seed plants.

BACKGROUND:and Purpose Recent randomized controlled trials have demonstrated consistent effectiveness of endovascular treatment (EVT) for acute ischemic stroke, leading to update on stroke management guidelines. We conducted this meta-analysis to assess the efficacy and safety of EVT overall and in subgroups stratified by age, baseline stroke severity, brain imaging feature, and anesthetic type. METHODS:Published randomized controlled trials comparing EVT and standard medical care alone were evaluated. The measured outcomes were 90-day functional independence (modified Rankin Scale ≤2), all-cause mortality, and symptomatic intracranial hemorrhage. RESULTS:Nine trials enrolling 2476 patients were included (1338 EVT, 1138 standard medical care alone). For patients with large vessel occlusions confirmed by noninvasive vessel imaging, EVT yielded improved functional outcome (pooled odds ratio [OR], 2.02; 95% confidence interval [CI], 1.64-2.50), lower mortality (OR, 0.75; 95% CI, 0.58-0.97), and similar symptomatic intracranial hemorrhage rate (OR, 1.12; 95% CI, 0.72-1.76) compared with standard medical care. A higher proportion of functional independence was seen in patients with terminus intracranial artery occlusion (±M1) (OR, 3.16; 95% CI, 1.64-6.06), baseline Alberta Stroke Program Early CT score of 8-10 (OR, 2.11; 95% CI, 1.25-3.57) and age ≤70 years (OR, 3.01; 95% CI, 1.73-5.24). EVT performed under conscious sedation had better functional outcomes (OR, 2.08; 95% CI, 1.47-2.96) without increased risk of symptomatic intracranial hemorrhage or short-term mortality compared with general anesthesia. CONCLUSIONS:Vessel-imaging proven large vessel occlusion, a favorable scan, and younger age are useful predictors to identify anterior circulation stroke patients who may benefit from EVT. Conscious sedation is feasible and safe in EVT based on available data. However, firm conclusion on the choice of anesthetic types should be drawn from more appropriate randomized controlled trials.

The ultimate goal in any biosensor development project is its use for actual sample detection. Recently, there has been an interest in biosensors with aptamers as bio-recognition elements, but reported examples all deal with standards, not human serum. In order to verify the differences of aptamer-based biosensor and antibody-based biosensor in clinical detection, a comparison of the performance of aptamer-based and antibody-based quartz crystal microbalance (QCM) biosensors for the detection of immunoglobulin E (IgE) in human serum was carried out. Aptamers (or antibodies) specific to IgE were immobilized on the gold surface of a quartz crystal. The frequency shifts of the QCM were measured. The linear range with the antibody (10–240 μg/L) compared to that of the aptamer (2.5–200 μg/L), but a lower detection limit could be observed in the aptamer-based biosensor. The reproducibility of the two biosensors was comparable. The aptamers were equivalent or superior to antibodies in terms of specificity and sensitivity. In addition, the aptamer receptors could tolerate repeated affine layer regeneration after ligand binding and recycling of the biosensor with little loss of sensitivity. When stored for three weeks, the frequency shifts of the aptamer-coated crystals were all greater than 90% of those on the response at the first day.

Epilepsy is a common chronic neurological disorder disease, and there is an urgent need for the development of novel anticonvulsant drugs. In this study, the anticonvulsant activities and neurotoxicity of 12 cinnamic acid derivatives substituted by fluorine, chlorine, bromine, and trifluoromethyl groups were screened by the maximal electroshock seizure (MES) and rotarod tests (Tox). Three of the tested compounds (compounds 3, 6 and 12) showed better anticonvulsant effects and lower neurotoxicity. They showed respective median effective dose (ED50) of 47.36, 75.72 and 70.65 mg/kg, and median toxic dose (TD50) of them was greater than 500 mg/kg, providing better protective indices. Meanwhile, they showed a pentylenetetrazol (PTZ) ED50 value of 245.2, >300 and 285.2 mg/kg in mice, respectively. Especially, the most active compound 3 displayed a prominent anticonvulsant profile and had lower toxicity. Therefore, the antiepileptic mechanism of 3 on glycosylation changes in chronic epilepsy in mice was further investigated by using glycomics techniques. Lectin microarrays results showed that epilepsy was closely related to abnormal glycosylation, and 3 could reverse the abnormal glycosylation in scPTZ-induced epilepsy in mice. This work can provide new ideas for future discovery of potential biomarkers for evaluation of antiepileptic drugs based on the precise alterations of glycopatterns in epilepsy.

K465 superalloy with high titanium and aluminum contents was easy to crack during laser metal deposition. In this study, the crack-free sample of K465/Stellite-6 laminated material was formed by laser metal deposition shaping to control the cracking behaviour in laser metal deposition of K465 superalloy. The microstructure differences between the K465 superalloy with cracking and the laminated material were discussed. The microstructure and intermetallic phases were analyzed through scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD). The results showed that the microstructure of K465/Stellite-6 laminated material samples consisted of continuous dendrites with a similar structure size in different alloy deposition layers, and the second dendrite arm spacing was finer compared with laser metal deposition shaping K465. The intermetallic phases in the different alloy deposition layers varied, and the volume fraction of carbides in K465 deposition layer of the laminated material was higher than only K465 deposition under the fluid flow effect. In addition, the composition and microhardness distribution of laminated materials variation occurred along the deposition direction.

This paper is intended to review advances in the botanical, phytochemical, traditional uses and pharmacological studies of the genus Trachelospermum. Until now, 138 chemical constituents have been isolated and characterized from these plants, particularly from T. asiaticum and T. jasminoides. Among these compounds, lignans, triterpenoids, and flavonoids are the major bioactive constituents. Studies have shown that plants from the genus Trachelospermum exhibit an extensive range of pharmacological properties both in vivo and in vitro, including anti-inflammatory, analgesic, antitumor, antiviral and antibacterial activities. In Traditional Chinese Medicine (TCM) culture, drugs that include T. jasminoides stems have been used to cure rheumatism, gonarthritis, backache and pharyngitis, although there are few reports concerning the clinical use and toxicity of these plants. Further attention should be paid to gathering information about their toxicology data, quality-control measures, and the clinical value of the active compounds from genus Trachelospermum.

This study explores the effect of citicoline on the permeability and expression of tight junction proteins (TJPs) in endothelial cells under hypoxia/aglycemia conditions. Hypoxia or oxygen and glucose deprivation (OGD) was utilized to induce endothelial barrier breakdown model on human umbilical vein endothelial cells (HUVECs) and mouse brain microvascular endothelial cells (bEnd.3s). The effect of citicoline on endothelial barrier breakdown models was determined at either low or high concentrations. FITC-Dextran flux was used to examine the endothelial permeability. The expression of TJPs was measured by immunofluorescence, Real-time PCR and Western Blot methods. Results showed that hypoxia or OGD increased the permeability of HUVECs accompanied with down-regulation of occludens-1 (ZO-1) and occludin at both mRNA and protein levels. Similarly in bEnd.3s, hypoxia increased the permeability and decreased the expression of ZO-1 and claudin-5. Citicoline treatment dose-dependently decreased the permeability in these two models, which paralleled with elevated expression of TJPs. The data demonstrate that citicoline restores the barrier function of endothelial cells compromised by hypoxia/aglycemia probably via up-regulating the expression of TJPs.

This study investigated the role of stromal cell-derived factor-1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) axis in brain and endothelial progenitor cells (EPCs), and explored the efficacy of CXCR4 primed EPCs in treating ischemic stroke in diabetes. The db/db diabetic and db/+ mice were used in this study. Levels of plasma SDF-1α and circulating CD34+CXCR4+ cells were measured. Brain SDF-1α and CXCR4 expression were quantified at basal and after middle cerebral artery occlusion (MCAO). In in vitro study, EPCs were transfected with adenovirus carrying null (Ad-null) or CXCR4 (Ad-CXCR4) followed with high glucose (HG) treatment for 4 days. For pathway block experiments, cells were pre-incubated with PI3K inhibitor or nitric oxide synthase (NOS) inhibitor for two hours. The CXCR4 expression, function and apoptosis of EPCs were determined. The p-Akt/Akt and p-eNOS/eNOS expression in EPCs were also measured. In in vivo study, EPCs transfected with Ad-null or Ad-CXCR4 were infused into mice via tail vein. On day 2 and 7, the cerebral blood flow, neurologic deficit score, infarct volume, cerebral microvascular density, angiogenesis and neurogenesis were determined. We found: 1) The levels of plasma SDF-1α and circulating CD34+CXCR4+ cells were decreased in db/db mice; 2) The basal level of SDF-1α and MCAO-induced up-regulation of SDF-1α/CXCR4 axis were reduced in the brain of db/db mice; 3) Ad-CXCR4 transfection increased CXCR4 expression in EPCs and enhanced EPC colonic forming capacity; 4) Ad-CXCR4 transfection prevented EPCs from HG-induced dysfunction (migration and tube formation) and apoptosis via activation of PI3K/Akt/eNOS signal pathway; 4) Ad-CXCR4 transfection enhanced the efficacy of EPC infusion in attenuating infarct volume and promoting angiogenesis and neurogenesis. Our data suggest that Ad-CXCR4 primed EPCs have better therapeutic effects for ischemia stroke in diabetes than unmodified EPCs do.