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The gut microbiota plays a crucial role in nutrient absorption, health maintenance and protecting the host against pathogen invasion. Studies have shown that the microbial composition and diversity of gut microbiota during early life can influence later growth and development. While specific pathogen-free (SPF) experimental animals are considered standard in biomedical, veterinary, and production research fields, little is known about the composition and diversity of the gut microbiota during the early developmental stages of these birds. Therefore, the present study aimed to explore the structure and changes of the gut microbiota during the early life of SPF chickens. Faecal DNA was sampled from randomly selected chickens, followed by high-throughput sequencing of the V3-V4 region of the 16S rRNA gene, at 11, 13, 15, and 17 days of age, designated as experimental groups D11, D13, D15, and D17. The sequencing results indicated that day 17 of life may be a turning point for gut microbiota colonisation, exhibiting a notable 51.98% increase in the number of operational taxonomic units compared to 15 days old birds. Analysis of faecal bacterial community compositions across the four age groups of SPF chickens showed dominance of Firmicutes, Proteobacteria, and Bacteroidetes in groups D11, D13, and D15, while Firmicutes, Proteobacteria, and Cyanobacteria were dominant in group D17. Additionally, group D17 had the highest number of bacterial genera and greatest diversity among the four groups tested. This study systematically elucidated the structure and dynamics of the gut microbiota during early life of chickens and provided a benchmark for future research on chicken gut microbiota. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), an essential adaptive intracellular pathway that relieves the stress. Although the UPR is an evolutionarily conserved and beneficial pathway, its chronic activation contributes to the pathogenesis of a wide variety of human disorders. The fidelity of UPR activation must thus be tightly regulated to prevent inappropriate signaling. The nonsense-mediated RNA decay (NMD) pathway has long been known to function in RNA quality control, rapidly degrading aberrant mRNAs, and has been suggested to regulate subsets of normal mRNAs. Here, we report that the NMD pathway regulates the UPR. NMD increases the threshold for triggering the UPR in vitro and in vivo, thereby preventing UPR activation in response to normally innocuous levels of ER stress. NMD also promotes the timely termination of the UPR. We demonstrate that NMD directly targets the mRNAs encoding several UPR components, including the highly conserved UPR sensor, IRE1α, whose NMD-dependent degradation partly underpins this process. Our work not only sheds light on UPR regulation, but demonstrates the physiological relevance of NMD's ability to regulate normal mRNAs.

Abstract [Objective] This study aims to explore the relationship between seed morphological and physical characteristics and seed vigor of Abies beshanzuensis, in order to provide a theoretical basis for further population renewal and protection of this endangered species, explaining its endangered mechanism, and studying its seed biology. [Methods] Using the endangered plant A . beshanzuensis as material, characteristic constants of the length, width, thickness, single grain weight, and RGB, etc. of the seeds of A . beshanzuensis were measured. Seed vigor was determined using TTC staining method, and their mathematical models were established. [Results] Significant differences were observed in R, B values, and single seed weight between vigorous and non-viable seeds of A . beshanzuensis. Single factor linear regression analysis showed that the correlation between seed vigor and single seed weight of A . beshanzuensis was the most significant, with R2=0.839. Two factor linear regression analysis showed that seed vigor had the most significant correlation with single seed weight and width, with R2=0.895. For multivariate linear regression analysis, R2 =0.978. However, no significant differences were observed in length, width, thickness, and G value between vigorous and non-viable seeds. [Conclusion] By using indicators such as R, B value, and single grain weight of A . beshanzuensis seeds, seeds with higher seed vigor can be screened. Multiple factor linear regression analysis predicts more accurately the seed vigor

The effect of anionic asphalt emulsion (AE) as partial replacement of Portland cement to enhance the damping properties of concrete was examined. Five concrete mixtures were designed and prepared, increasing AE content from 0 % to 40 % in overall binder volume, in 10 % increments. Loss factor, dynamic moduli, resonant frequencies, and compressive strength were obtained at the age of 7, 28, 90, and 180 days. Results show that the loss factor of concrete increased as the asphalt content increased, whereas the dynamic modulus and resonant frequency decreased. In addition to the viscous damping contributed by asphalt droplets, the more porous microstructure and weaker interfacial transition zones in AE modified concrete can also enhance the damping properties. However, an inverse correlation between concrete strength and damping can be observed with increasing AE content, where the substitution of AE results in a significant decrease in the compressive strength of concrete. Therefore, the anionic AE modified concrete seems to be more suitable for non-structural application where strength is not a key requirement.

In this paper, a non-linear stochastic model was constructed to introduce psychological capital as a random disturbance and predict students’ entrepreneurial intentions. Then, we conducted a differential analysis of students’ psychological capital on indicators of gender, family economic status and parents’ attitudes toward their children’s entrepreneurship, and also tested the mediating effects of innovation efficacy and perceived behavioral control to reveal the inner mechanism of the psychological capital of college students’ innovation and entrepreneurship. Finally, a psychological support system for college students’ entrepreneurship was constructed, including three dimensions a positive organizational system, positive emotional experience, and positive personality traits. The study showed that the direct effect of psychological capital on entrepreneurial intention was significant, β = 0.15, t = 3.19, p < 0.01, and overall significant. Innovative efficacy significantly and positively predicted perceived behavioral control β=0.48, t=12.67, p

The flow field and velocity distribution were investigated by computational fluid dynamics (CFD) in a oxidation ditch (OD) with an semi-circular guiding wall to improve the flow mixture character and reduce energy consumption. The time-averaged gas-liquid two phase flow equations closed by the renormalized group (RNG) κ-ε model were solved by the semi-implicit method for pressure- linked equations (SIMPLE) algorithm, and the volume of fluid (VOF) method was applied to track the flow surface. The simulation results show that: (1) adding a semi-circular guiding wall can obviously reduce the size of circulation zone so as to make the effective volume of the OD become greater, and can result in the flow field distribution become more uniform so as to prevent sludge from settling, (2) the additional semi-circular guiding wall can make the percentage, P, of the VOF with a velocity greater than 0.3 m/s in the ditch be increased from 40.8% to 47.6% compared to that of the non-guiding wall, which is conducive to reducing sludge deposition in the OD, and (3) the additional semi-circular guiding wall can make the velocity value of outer high-speed flow decrease at the exit of the bend while the velocity value of inner low-speed flow increase, which makes the difference of velocity values between the inner and outer of the exit of the bend become small so as to obtain more uniform flow, and can effectively prevent sludge deposition in the bend of OD. The numerical simulation is an effective method to study the hydraulic characteristics of ODs, and simulation results have a certain guiding significance for reducing sludge deposition and improving the sewage treatment efficiency of ODs. [ABSTRACT FROM AUTHOR]

The Indonesian Government takes serious measure on the future prospect of the teacher education graduates who are considered not to have a standardized competence ability to become a professional teacher. It inflicted some responses that opposed with the implementation of the program. This issue highlights the need for a more thorough investigation on the legitimacy of new teachers in Indonesia, as well as their quality. The goal of this study is to learn about pre-service teachers’ perceptions of their own competency and readiness to teach. This quantitative study used internet-based questionnaires to collect the data. The participants were 67 undergraduate students of university in Lamongan, East Java Province. The result of this research showed that p value (.258) is higher () than ɑ value (.05). It means that there were no correlation between pre-service teachers’ perception of their competence and their readiness for teaching profession. Nevertheless, the pre-service teachers have a positive perception regarding their competence and readiness to teach in a professional setting. By realizing and considering their competence and readiness for the teaching profession, they willfeel more confident and ready to face the real environment of teaching as a profession.

Abstract We previously developed TANTIGEN, a comprehensive online database cataloging more than 1000 T cell epitopes and HLA ligands from 292 tumor antigens. In TANTIGEN 2.0, we significantly expanded coverage in both immune response targets (T cell epitopes and HLA ligands) and tumor antigens. It catalogs 4,296 antigen variants from 403 unique tumor antigens and more than 1500 T cell epitopes and HLA ligands. We also included neoantigens, a class of tumor antigens generated through mutations resulting in new amino acid sequences in tumor antigens. TANTIGEN 2.0 contains validated TCR sequences specific for cognate T cell epitopes and tumor antigen gene/mRNA/protein expression information in major human cancers extracted by Human Pathology Atlas. TANTIGEN 2.0 is a rich data resource for tumor antigens and their associated epitopes and neoepitopes. It hosts a set of tailored data analytics tools tightly integrated with the data to form meaningful analysis workflows. It is freely available at http://projects.met-hilab.org/tadb .

[Objectives]In order to accurately understand the temperature inside the flame and the distribution of soot concentration,[Methods]the distribution of the two-dimensional temperature and the soot volume fraction inverted from the spectral intensity image of the flame was studied using a hyper-spectrometer. Firstly,a hyper-spectrometer was used to capture the laboratory's vinyl laminar diffusion flame to obtain a high-resolution image containing multi-spectral information. Then, the wavelength in the image was analyzed and screened,the multi-wavelength radiation intensity information was obtained by calibrating the blackbody furnace,and the two-dimensional distribution of the flame temperature and the soot volume fraction was obtained by inversion.[Results]Comparing the obtained flame temperature with the results from other literature,the maximum temperature deviation is 2.77%, and the results are in good agreement,[Conclusions]indicating the accuracy of the distribution of temperature and soot volume fraction.

To explore the feasibility of using metakaolin and limestone in steam-cured concrete, mechanical property, sorptivity and microstructure of steam-cured concrete incorporated with the combination of metakaolin-limestone powder were studied, with steam-cured concrete incorporated with ground granulated blast furnace slag and fly ash as a reference. Due to the high reactivity of metakaolin, the presence of metakaolin reduces the heterogeneous distribution of hydration products, thereby resulting in a refined microstructure and lowered sorptivity of steam-cured concrete. The synergistic effect of metakaolin with limestone powder leads to further improvements on strength, sorptivity associated with a more uniform microstructure at late ages. Moreover, concrete incorporated with metakaolin-limestone powder and steam-cured at 40 °C can gain a comparable early strength (1 day) with concrete incorporated with the combination of ground granulated blast furnace slag - fly ash, and steam-cured at 60 °C; this indicates that the incorporation of metakaolin enables to reduce steam curing temperature without compromising early strength gain, which is of significance for mitigating steam-curing induced detrimental effects and reducing energy consumption. Keywords: Metakaolin, Limestone, Steam curing, Compressive strength, Sorptivity, Microstructure

In view of the limited of the space, the weight of the carrier and the power consumption of the missile, this paper designed a data recorder system with high reliability, low power consumption and small size. The system could receive video data of scene and then realize hardware compressed storage in H.264 format. At the same time, it can also record the flight status data of the missile in real time and store the data in high-speed and large-capacity SD card, which is easy to read back and process the collected data.

To improve the environmental efficiency of the reverse filling system, three strategies aim to optimize the packing density, and the mechanical property were adopted in this study. Based on the compressive packing model (CPM), the relationship between the D50 ratio and maximum theoretical packing density for a reverse filling system with 25% and 30% superfine Portland cement was established. For comparison, silica fume and steel fiber were also added to the reverse filling system, respectively. The improvement of packing density by adjusting the D50 ratio was verified through the minimum water demand method, CPM, and modified Andreasen and Andersen (MAA) model. Compared to the reverse filling system added with 3 wt % silica fume, which possesses a comparable mechanical property with the optimized group (adjusted D50 ratio), the incorporation of steel fiber shows a more significant increase. The environmental efficiency of all the samples was quantified into five aspects through the calculation based on the mix proportion, compressive strength, and hydration degree. The comprehensive evaluation demonstrated that the optimized reverse filling system exerts a lower environmental impact and possesses a much higher cement use efficiency compared to the majority of ultra-high performance concrete (UHPC)/ ultra-high performance fiber-reinforced concrete (UHPFRC) reported in published papers.

La apreciación que los viajeros europeos por el fandango evolucionó desde principios del siglo dieciocho hasta finales del diecinueve. Hacia la segunda mitad del dieciocho, y especialmente durante el diecinueve, los viajeros se entusiasmaron por el baile que con frecuencia comparaban con los bailes que se ejecutaban en Cádiz durante el Imperio Romano. A finales del siglo diecinueve los viajeros franceses se enamoraron especialmente de la sensualidad de las bailaoras, cuyos movimientos describieron con gran detalle para sus lectores. Gradualmente, otros viajeros, en búsqueda de espectáculos más apasionados, comenzaron a preferir bailes como el Olé y el Vito. En 1889, España presentó a un grupo de bailaoras a la Exposición Universal en París. El escritor Catulle Mendès, entusiasmado por la apasionada y exótica exhibición, describió sus movimientos “como salamandras en el fuego,” haciendo eco de viejos estereotipos que a lo largo del tiempo los viajeros europeos asociaban especialmente con las mujeres gitanas.

European funded research into the Recursive Inter-Network Architecture (RINA) started with IRATI, which developed an initial prototype implementation for OS/Linux. IRATI was quickly succeeded by the PRISTINE project, which developed different policies, each tailored to specific use cases. Both projects were development-driven, where most experimentation was limited to unit testing and smaller scale integration testing. In order to assess the viability of RINA as an alternative to current network technologies, larger scale experimental deployments are needed. The opportunity arose for a project that shifted focus from development towards experimentation, leveraging Europe’s investment in Future Internet Research and Experimentation (FIRE+) infrastructures. The ARCFIRE project took this next step, developing a user-friendly framework for automating RINA experiments. This paper reports and discusses the implications of the experimental results achieved by the ARCFIRE project, using open source RINA implementations deployed on FIRE+ Testbeds. Experiments analyze the properties of RINA relevant to fast network recovery, network renumbering, Quality of Service, distributed mobility management, and network management. Results highlight RINA properties that can greatly simplify the deployment and management of real-world networks; hence, the next steps should be focused on addressing very specific use cases with complete network RINA-based networking solutions that can be transferred to the market.

Multifunction elastic warp-knitted fabrics were fabricated on a crochet machine with the use of metal composite yarns/viscose yarn and bamboo polyester/ crisscross-section polyester hybrid yarns as the front face and back face of the knitted fabric structure, respectively. We investigated the effect of the blend ratio of bamboo charcoal/ crisscross-section polyester multiply yarns on the fabric's moisture comfort properties, such as water vapour transmission (WVT), water evaporation rate (WER), and water absorbency. The results showed that blending ratio significantly influenced WVT and WER. Moreover, antibacterial activity of the elastic warp- knitted fabric was tested against Staphylococcus aureus and Escherichia coli in accordance with AATCC 90-2011. Finally, the extension- stress value curves were used to analyse the elastic stretching property, and the fabric exhibited greater breaking elongation and lower stress value in the walewise than in the weft direction.

La apreciación que los viajeros europeos por el fandango evolucionó desde principios del siglo dieciocho hasta finales del diecinueve. Hacia la segunda mitad del dieciocho, y especialmente durante el diecinueve, los viajeros se entusiasmaron por el baile que con frecuencia comparaban con los bailes que se ejecutaban en Cádiz durante el Imperio Romano. A finales del siglo diecinueve los viajeros franceses se enamoraron especialmente de la sensualidad de las bailaoras, cuyos movimientos describieron con gran detalle para sus lectores. Gradualmente, otros viajeros, en búsqueda de espectáculos más apasionados, comenzaron a preferir bailes como el Olé y el Vito. En 1889, España presentó a un grupo de bailaoras a la Exposición Universal en París. El escritor Catulle Mendès, entusiasmado por la apasionada y exótica exhibición, describió sus movimientos como salamandras en el fuego, haciendo eco de viejos estereotipos que a lo largo del tiempo los viajeros europeos asociaban especialmente con las mujeres gitanas.

A phenotypic high-throughput cell culture screen was performed to identify compounds that prevented proliferation of the human Papilloma virus type 16 (HPV-16) transformed cell line Ca Ski. A series of quinoxaline compounds exemplified by Compound 1 was identified. Testing against a panel of cell lines demonstrated that Compound 1 selectively inhibited replication of all HPV-16, HPV-18, and HPV-31 transformed cell lines tested with 50% Inhibitory Concentration (IC50) values of 2 to 8 μM relative to IC50 values of 28 to 73 μM in HPV-negative cell lines. Treatment with Compound 1 resulted in a cascade of multiple apoptotic events, including selective activation of effector caspases 3 and 7, fragmentation of cellular DNA, and PARP (poly(ADP-ribose) polymerase) cleavage in HPV-positive cells relative to HPV-negative cells. Unregulated proliferation of HPV transformed cells is dependent on the viral oncogenes, E6 and E7. Treatment with Compound 1 resulted in a decrease in HPV E7 protein in Ca Ski cells. However, the timing of this reduction relative to other effects of compound treatment suggests that this was a consequence, rather than a cause, of the apoptotic cascade. Likewise, compound treatment resulted in no obvious effects on the E6- and E7- mediated down regulation of p53 and Rb, or their downstream effectors, p21 or PCNA. Further investigation of apoptotic signals induced by Compound 1 revealed cleavage of Caspase-8 in HPV-positive cells as early as 2 hours post-treatment, suggesting the compound initiates apoptosis through the extrinsic, death receptor-mediated, pathway of cell death. These studies provide proof of concept that cells transformed by oncogenic Papillomaviruses can be selectively induced to undergo apoptosis by compound treatment.

In clause features of establishing social and political terminology and using in mass media of China in the end of XIX are considered.

Este ensayo explora el diálogo de Pardo Bazán con la ficción representativa realista, con sus obsesiones voyeuristas, revisitando ciertos pasajes de la novela Dulce Dueño y revisando investigaciones feministas recientes (Bieder, Bacon, Medina y Kirkpatrick) que consideran la novela como una subversión, en distintos grados, de la mirada masculina. Mientras que estos críticos ven en la novela, acertadamente, un ademán hacia la modernidad, se examina también aquí su ojeada retrospectiva hacia anteriores tramas que exploran la subjetividad femenina y que imaginan varias maneras de demostrar que la mujer tenía corazón.

OBJECTIVE: To ascertain the perspectives of family-planning service providers in eight sites in China on the provision of sexual and reproductive health services to unmarried young people. METHODS: Data were drawn from a survey of 1927 family-planning workers and 16 focus group discussions conducted in eight sites in China in 1998-99. FINDINGS: Family-planning workers recognized the need to protect the sexual health of unmarried young people and were unambiguous about the need for government agencies to provide information and education on sexual and reproductive health to unmarried young people; however, perceptions about the appropriate age for and content of such education remained conservative. While about 70% of family-planning workers were willing to provide contraceptives to unmarried young people, and about 60% approved government provision of contraceptive services to unmarried young people, only one quarter agreed that the services could be extended to senior high schools. CONCLUSION: Family-planning workers in China are ambivalent about the provision of sexual and reproductive health services to unmarried young people, which potentially poses a significant obstacle to the adoption of safe sex behaviours by young people, as well as to the provision of sexual and reproductive health information and services to young unmarried people in China. Training programmes for family-planning workers are urgently needed to address this issue.

Due to recent rapid commercial and industrial development, mechanical equipment is supplemented massively in the factory and thus mechanical operation causes noise which distresses living at home. In livelihood, neighborhood, transportation equipment, jobsite construction noises impact on quality of life not only factory noise. This study aims to preparation technique and property evaluation of porous sound-absorbing/thermal-insulating composites. Hollow three-dimensional crimp PET fibers blended with low-melting PET fibers were fabricated into hollow PET/low-melting PET nonwoven after opening, blending, carding, lapping and needle-bonding process. Then, hollow PET/low-melting PET nonwovens were laminated into sound-absorbing/thermal-insulating composites by changing sequence of needle-bonding and thermal-treatment. The optimal thermal-treated sequence was found by tensile strength, tearing strength, sound-absorbing coefficient and thermal conductivity coefficient tests of porous composites.

This study proposes making filter materials with polypropylene (PP) and low-melting point (LPET) fibers. The influences of temperatures and times of heat treatment on the morphology of thermal bonding points and average pore size of the PP/LPET filter materials. The test results indicate that the morphology of thermal bonding points is highly correlated with the average pore size. When the temperature of heat treatment is increased, the fibers are joined first with the thermal bonding points, and then with the large thermal bonding areas, thereby decreasing the average pore size of the PP/LPET filter materials. A heat treatment of 110 °C for 60 seconds can decrease the pore size from 39.6 μm to 12.0 μm.

Along with the advancement of the construction of ecological civilization, low-carbon economy and low-carbon tourism are increasingly affecting the production and life style of human beings. Low carbon tourism is in the process of tourism development, through the use of low-carbon technologies, promote carbon absorbing mechanism and advocate low carbon tourism consumption to obtain higher tourism experience quality and greater tourism economic, social and environmental benefits of a sustainable development of tourism in new ways . Low carbon has become a recognized future development direction of the tourism industry. Closely linked to this paper, vigorously develop low carbon tourism industry requirements, to Lin an, Zhejiang Tian mu village, for example, through on-the-spot investigation, the problems existed in the village rural tourism low carbon analysis, and put forward the corresponding countermeasures, in order to rural tourism and low-carbon development in our province to find a feasible and with a demonstration of the significance of the road, and for other areas to carry out low carbon tourism experience.

The swine wastewater has the characteristics of high concentration of organic matter, suspended solids and more high ammonia nitrogen, odor, complex pollution ingredient and large emissions. Microbial fuel cells (MFC) is an electrochemical and biological systems related to chemical energy into electrical energy. A two-chambered cubic microbial fuel cell was used to evaluate the effect of a novel 3D electrode which made of iron and copper on the electricity generation. The swine wastewater containing total chemical oxygen demand (TCOD) 3300±300 mg/L was used as the feedstock in anode chamber, and the potassium ferricyanide was used as electron acceptor in cathode chamber. The MFC reactor was incubated with the initial pH 7.0 in a air-shaker with a temperature (ca. 35°C) and 100 rpm in fed-batch mode. A fixed external resistance (R) of 100 Ω was connected between the electrodes and the closed circuit potentials of the MFCs were recorded every 2 min. The results show that using iron 3D electrode has the peak electricity generation of 176 mV at the first two day and maintained the stable electricity voltage of 110 mV during the 5th to 15th days. The COD removal efficiency could reach 80%. Using copper 3D electrode only can generate the peak electricity of 33.1 mV and stable electricity of 27 mV with the COD removal efficiency of 70%.

Nonwoven fabrics have merits, and for example, they can be simply and quickly processed with a variety of materials and an easily changeable manufacturing process. This study aims to examine the influences of the addition of sodium alginate (SA) and the concentration of calcium chloride (CaCl2) on the properties of the composite nonwoven fabrics. Chitosan (CS) micro-particles and SA solution are cross-linked with CaCl2 with various concentrations, combined with farir heat preservative staples (FT)/cotton (C) nonwoven fabrics, and then freeze-dried to form CS/SA/FT/C composite nonwoven fabrics. Afterwards, physical property tests are performed on the resulting composite nonwoven fabrics to determine their properties as related to various concentrations of CaCl2. The addition of SA decreases the water vapor permeability of FT/C nonwoven fabrics by 15 %, but the concentrations of CaCl2 do not influence the water vapor permeability. Compared to FT/C nonwoven fabrics, CS/SA/FT/C composite nonwoven fabrics have significantly lower water absorbency and water vapor permeability, but a greater stiffness.

The fuzzy clustering algorithm is to classify the data or indicators with a greater degree of similarity based on the principle of the same type of individuals possessing a greater similarity, and different types of individuals possessing differences, establish clear category boundaries, form any shape of relationship clusters in the solving process, and input the research indicators at random, in order to accurately analyze the significance of the indicators in the algorithm. The evaluation value of the clustering analysis can be obtained by the establishment of the fuzzy factor set based on the membership analysis, and the evaluation result can be analyzed through reference to the evaluation indicators of the fuzzy clustering analysis. The “micro-lecture” English teaching mode can be estimated and the analysis indicators can be rationally established based on the fuzzy clustering analysis algorithm, with better algorithm applicability.

As a system distinguishing decision, the gray decision can solve most of the issues related to the gray fuzzy multi-criteria decision in real life. This paper establishes a gray fuzzy decision model based the English teaching quality, in order to evaluate the English teaching quality. The model defines the fuzzy set according to the index attributes, and gives the membership for the gray fuzzy relations between indices, and then obtains the weight results of each index based on the calculation of the gray fuzzy. Finally, this paper verifies the availability of the model through the actual teaching examples.

This paper researches the issues of English teaching by the use of the group decision-making hierarchical structural assessment model, which aims at clearly resolving the problems in the examination of the current English teaching, and quickly provides effective solutions. The group decision-making hierarchical structural assessment model can ultimately construct a quantitative index assessment system based on the weight analysis and combined with the multi-index quantification mode, thus flexibly and effectively solving fuzzy and complex problems. This paper will build a group decision-making hierarchical structural assessment model for English teaching in China, establish factors affecting level and measures scheme level, make a detailed quantita-tive weight evaluation analysis and find out an educational method that can effectively enhance the practicability of English in China.

This paper first makes a brief introduction on the research progress of artificial intelligence, then introduces the basic structure of the whole English assisted learning system from the angle of system functional requirements, and finally discusses the realization of functions of the English assisted learning system under the support of rule-based data mining, aiming at attracting more attentions.

Although up to 80% small cell lung cancer (SCLC) patients' response is good for first-line chemotherapy regimen, most patients develop recurrence of the disease within weeks to months. Here, we report cytostatic effect of leflunomide (Leflu) and teriflunomide (Teri) on SCLC cell proliferation through inhibition of DRP1 phosphorylation at Ser 616 and decreased mitochondrial fragmentation. When administered together, Teri and carboplatin (Carbo) act synergistically to significantly inhibit cell proliferation and DRP1 phosphorylation, reduce abundance of intermediates in pyrimidine de novo pathway, and increase apoptosis and DNA damage. Combination of Leflu&Carbo has anti-tumorigenic effect in vivo . Additionally, lurbinectedin (Lur) and Teri potently and synergistically inhibited spheroid growth and depleted uridine and DRP1 phosphorylation in mouse tumors. Our results suggest combinations of Carbo and Lur with Teri or Leflu are efficacious and underscore how the relationship between DRP1/DHODH and mitochondrial plasticity serves as a potential therapeutic target to validate these treatment strategies in SCLC clinical trials., Competing Interests: R.S., S.T.R, and T.M. report a patent pending for combination treatment of teriflunomide&leflunomide with carboplatin&lurbinectedin., (© 2024 The Authors.)

Although midnolin has been studied for over 20 years, its biological roles in vivo remain largely unknown, especially due to the lack of a functional animal model. Indeed, given our recent discovery that the knockdown of midnolin suppresses liver cancer cell tumorigenicity and that this antitumorigenic effect is associated with modulation of lipid metabolism, we hypothesized that knockout of midnolin in vivo could potentially protect from nonalcoholic fatty liver disease (NAFLD) which has become the most common cause of chronic liver disease in the Western world. Accordingly, in the present study, we have developed and now report on the first functional global midnolin knockout mouse model. Although the overwhelming majority of global homozygous midnolin knockout mice demonstrated embryonic lethality, heterozygous knockout mice were observed to be similar to wild-type mice in their viability and were used to determine the effect of reduced midnolin expression on NAFLD. We found that global heterozygous midnolin knockout attenuated the severity of NAFLD in mice fed a Western-style diet, high in fat, cholesterol, and fructose, and this attenuation in disease was associated with significantly reduced levels of large lipid droplets, hepatic free cholesterol, and serum LDL, with significantly differential gene expression involved in cholesterol/lipid metabolism. Collectively, our results support a role for midnolin in regulating cholesterol/lipid metabolism in the liver. Thus, midnolin may represent a novel therapeutic target for NAFLD. Finally, our observation that midnolin was essential for survival underscores the broad importance of this gene beyond its role in liver biology. NEW & NOTEWORTHY We have developed and now report on the first functional global midnolin knockout mouse model. We found that global heterozygous midnolin knockout attenuated the severity of nonalcoholic fatty liver disease (NAFLD) in mice fed a Western-style diet, high in fat, cholesterol, and fructose, and this attenuation in disease was associated with significantly reduced levels of large lipid droplets, hepatic free cholesterol, and serum LDL, with significantly differential gene expression involved in cholesterol/lipid metabolism.

Impaired angiogenesis in diabetes is a key process contributing to ischemic diseases such as peripheral arterial disease. Epigenetic mechanisms, including those mediated by long noncoding RNAs (lncRNAs), are crucial links connecting diabetes and the related chronic tissue ischemia. Here we identify the lncRNA that enhances endothelial nitric oxide synthase (eNOS) expression (LEENE) as a regulator of angiogenesis and ischemic response. LEENE expression was decreased in diabetic conditions in cultured endothelial cells (ECs), mouse hind limb muscles, and human arteries. Inhibition of LEENE in human microvascular ECs reduced their angiogenic capacity with a dysregulated angiogenic gene program. Diabetic mice deficient in Leene demonstrated impaired angiogenesis and perfusion following hind limb ischemia. Importantly, overexpression of human LEENE rescued the impaired ischemic response in Leene-knockout mice at tissue functional and single-cell transcriptomic levels. Mechanistically, LEENE RNA promoted transcription of proangiogenic genes in ECs, such as KDR (encoding VEGFR2) and NOS3 (encoding eNOS), potentially by interacting with LEO1, a key component of the RNA polymerase II-associated factor complex and MYC, a crucial transcription factor for angiogenesis. Taken together, our findings demonstrate an essential role for LEENE in the regulation of angiogenesis and tissue perfusion. Functional enhancement of LEENE to restore angiogenesis for tissue repair and regeneration may represent a potential strategy to tackle ischemic vascular diseases.

Concordant transcriptional regulation can generate multiple gene products that collaborate to achieve a common goal. Here we report a case of concordant transcriptional regulation that instead drives a single protein to be produced in the same cell type from divergent promoters. This gene product-the RHOX5 homeobox transcription factor-is translated from 2 different mRNAs with different 5' untranslated regions (UTRs) transcribed from alternative promoters. Despite the fact that these 2 promoters-the proximal promoter (Pp) and the distal promoter (Pd)-exhibit different patterns of tissue-specific activity, share no obvious sequence identity, and depend on distinct transcription factors for expression, they exhibit a remarkably similar expression pattern in the testes. In particular, both depend on androgen signaling for expression in the testes, where they are specifically expressed in Sertoli cells and have a similar stage-specific expression pattern during the seminiferous epithelial cycle. We report evidence for 3 mechanisms that collaborate to drive concordant Pp/Pd expression. First, both promoters have an intrinsic ability to respond to androgen receptor and androgen. Second, the Pp acts as an enhancer to promote androgen-dependent transcription from the Pd. Third, Pd transcription is positively autoregulated by the RHOX5 protein, which is first produced developmentally from the Pp. Together, our data support a model in which the Rhox5 homeobox gene evolved multiple mechanisms to activate both of its promoters in Sertoli cells to produce Rhox5 in an androgen-dependent manner during different phases of spermatogenesis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The integration of cellular status with metabolism is critically important and the coupling of energy production and cellular function is highly evolutionarily conserved. This has been demonstrated in stem cell biology, organismal, cellular and tissue differentiation and in immune cell biology. However, a molecular mechanism delineating how cells coordinate and couple metabolism with transcription as they navigate quiescence, growth, proliferation, differentiation and migration remains in its infancy. The extreme N-termini of the Kat3 coactivator family members, CBP and p300, by far the least homologous regions with only 66% identity, interact with members of the nuclear receptor family, interferon activated Stat1 and transcriptionally competent β-catenin, a critical component of the Wnt signaling pathway. We now wish to report based on multiomic and functional investigations, utilizing p300 knockdown, N-terminal p300 edited and p300 S89A edited cell lines and p300 S89A knockin mice, that the N-termini of the Kat3 coactivators provide a highly evolutionarily conserved hub to integrate multiple signaling cascades to coordinate cellular metabolism with the regulation of cellular status and function.

Extra-nodal natural killer/T-cell lymphoma, nasal type (ENKTCL) is a highly aggressive lymphoma, where the tumor suppressor gene (TSG) PRDM1 is frequently lost/inactivated. We employed two different CRISPR/Cas9 approaches to generate PRDM1-/- primary NK cells to study its role in NK-cell homeostasis. PRDM1-/- NK cells showed a marked increase in cloning efficiency, higher proliferation rate and less apoptosis compared with their wild type counterparts. Gene expression profiling demonstrated a marked enrichment in pathways associated with proliferation, cell cycle, MYC, MYB and TCR/NK signaling in PRDM1-/- NK cells, but pathways associated with normal cellular functions including cytotoxic functions were down-regulated, suggesting that the loss of PRDM1 shifted NK cells toward proliferation and survival rather than the performance of its normal functions. We were also able to further modify a PRDM1 deleted clone to introduce heterozygous deletions of common TSG in ENKTCL such as TP53, DDX3X, or PTPN6. We have established an in vitro model to elucidate the major pathways through which PRDM1 mediates its homeostatic control of NK-cells. This approach can be applied to the study of other relevant genetic lesions and oncogenic collaborations in lymphoma pathogenesis.

Polysaccharide from Phellinus igniarius (PPI) is known for its immune-regulating effect with low toxicity. Toll like receptor 4 (TLR4) is important in both innate and adaptive immune responses and considered to be a promising target for new immune adjuvants. In this study, PPI was investigated for its effect on activating TLR4 in RAW264.7 and peritoneal macrophages. The adjuvant potential of PPI was evaluated in OVA-immunized mice. The results showed PPI treatment significantly increased the secretion and the mRNA expression of both MyD88 dependent and TRIF dependent cytokines. IRAK-1, a key molecule on the downstream of MyD88, was polyubiquitinated while IRF-3, another key molecule on the downstream of TRIF, was phosphorylated obviously after the treatment of PPI. The phosphorylation of molecules involved in both NF-κB pathway and MAPK pathway were significantly up-regulated after PPI treatment. In addition, the effects of PPI on the macrophages almost completely disappeared after treating the cells with the TLR4 antagonist TAK-242. Further in vivo results showed PPI significantly increased the serum OVA-specific antibody and the OVA-specific spleen cell proliferation. Taken together, PPI can specifically stimulate TLR4 and activate both MyD88 and TRIF pathways. PPI has immune adjuvant activity and may become a new potential immune adjuvant., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Expression of nuptial color is usually energetically costly, and is therefore regarded as an 'honest signal' to reflect mate quality. In order to choose a mate with high quality, both sexes may benefit from the ability to precisely evaluate their mates through optimizing visual systems which is in turn partially regulated by opsin gene modification. However, how terrestrial vertebrates regulate their color vision sensitivity is poorly studied. The green-spotted grass lizard Takydromus viridipunctatus is a sexually dimorphic lizard in which males exhibit prominent green lateral colors in the breeding season. In order to clarify relationships among male coloration, female preference, and chromatic visual sensitivity, we conducted testosterone manipulation with mate choice experiments, and evaluated the change of opsin gene expression from different testosterone treatments and different seasons. The results indicated that males with testosterone supplementation showed a significant increase in nuptial color coverage, and were preferred by females in mate choice experiments. By using quantitative PCR (qPCR), we also found that higher levels of testosterone may lead to an increase in rhodopsin-like 2 (rh2) and a decrease in long-wavelength sensitive (lws) gene expression in males, a pattern which was also observed in wild males undergoing maturation as they approached the breeding season. In contrast, females showed the opposite pattern, with increased lws and decreased rh2 expression in the breeding season. We suggest this alteration may facilitate the ability of male lizards to more effectively evaluate color cues, and also may provide females with the ability to more effectively evaluate the brightness of potential mates. Our findings suggest that both sexes of this chromatically dimorphic lizard regulate their opsin expression seasonally, which might play an important role in the evolution of nuptial coloration.

Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation pathway that acts on RNAs terminating their reading frames in specific contexts. NMD is regulated in a tissue-specific and developmentally controlled manner, raising the possibility that it influences developmental events. Indeed, loss or depletion of NMD factors have been shown to disrupt developmental events in organisms spanning the phylogenetic scale. In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (ID) and are strongly associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ). Here, we report the generation and characterization of mice harboring a null Upf3b allele. These Upf3b-null mice exhibit deficits in fear-conditioned learning, but not spatial learning. Upf3b-null mice also have a profound defect in prepulse inhibition (PPI), a measure of sensorimotor gating commonly deficient in individuals with SCZ and other brain disorders. Consistent with both their PPI and learning defects, cortical pyramidal neurons from Upf3b-null mice display deficient dendritic spine maturation in vivo. In addition, neural stem cells from Upf3b-null mice have impaired ability to undergo differentiation and require prolonged culture to give rise to functional neurons with electrical activity. RNA sequencing (RNAseq) analysis of the frontal cortex identified UPF3B-regulated RNAs, including direct NMD target transcripts encoding proteins with known functions in neural differentiation, maturation and disease. We suggest Upf3b-null mice serve as a novel model system to decipher cellular and molecular defects underlying ID and neurodevelopmental disorders.

The optimal expression of endothelial nitric oxide synthase (eNOS), the hallmark of endothelial homeostasis, is vital to vascular function. Dynamically regulated by various stimuli, eNOS expression is modulated at transcriptional, post-transcriptional, and post-translational levels. However, epigenetic modulations of eNOS, particularly through long non-coding RNAs (lncRNAs) and chromatin remodeling, remain to be explored. Here we identify an enhancer-associated lncRNA that enhances eNOS expression (LEENE). Combining RNA-sequencing and chromatin conformation capture methods, we demonstrate that LEENE is co-regulated with eNOS and that its enhancer resides in proximity to eNOS promoter in endothelial cells (ECs). Gain- and Loss-of-function of LEENE differentially regulate eNOS expression and EC function. Mechanistically, LEENE facilitates the recruitment of RNA Pol II to the eNOS promoter to enhance eNOS nascent RNA transcription. Our findings unravel a new layer in eNOS regulation and provide novel insights into cardiovascular regulation involving endothelial function.

A needle-free delivery system may lead to improved satisfaction and compliance, as well as reduced anxiety among patients requiring frequent or ongoing injections. This report describes a first-in-man assessment comparing Portal Instruments' innovative needle-free injection system with subcutaneous injections using a 27G needle. Forty healthy volunteer participants each received a total of four injections of 1.0 mL sterile saline solution, two with a standard subcutaneous injection using a 27G needle, and two using the Portal injection system. Perception of pain was measured using a 100-mm visual analog scale (VAS). Injection site reactions were assessed at 2 min and at 20-30 min after each injection. Follow-up contact was made 24-48 h after the injections. Subject preference regarding injection type was also assessed. VAS pain scores at Portal injection sites met the criteria to be considered non-inferior to the pain reported at 27G needle injection sites (i.e., upper 95% confidence bound less than +5 mm). Based on a mixed effects model, at time 0, accounting for potential confounding variables, the adjusted difference in VAS scores indicated that Portal injections were 6.5 mm lower than the 27G needle injections (95% CI -10.5, -2.5). No clinically important adverse events were noted. Portal injections were preferred by 24 (60%) of the subjects (P = 0.0015). As an early step in the development of this new needle-free delivery system, the current study has shown that a 1.0-mL saline injection can be given with less pain reported than a standard subcutaneous injection using a 27G needle.

Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Gene duplication is a major evolutionary force driving adaptation and speciation, as it allows for the acquisition of new functions and can augment or diversify existing functions. Here, we report a gene duplication event that yielded another outcome--the generation of antagonistic functions. One product of this duplication event--UPF3B--is critical for the nonsense-mediated RNA decay (NMD) pathway, while its autosomal counterpart--UPF3A--encodes an enigmatic protein previously shown to have trace NMD activity. Using loss-of-function approaches in vitro and in vivo, we discovered that UPF3A acts primarily as a potent NMD inhibitor that stabilizes hundreds of transcripts. Evidence suggests that UPF3A acquired repressor activity through simple impairment of a critical domain, a rapid mechanism that may have been widely used in evolution. Mice conditionally lacking UPF3A exhibit "hyper" NMD and display defects in embryogenesis and gametogenesis. Our results support a model in which UPF3A serves as a molecular rheostat that directs developmental events., (Copyright © 2016 Elsevier Inc. All rights reserved.)

MicroRNAs (miRNAs) are known to play diverse roles in the regulation of vertebrate development. To investigate miRNA-target mRNA relationships in embryonic development, we have carried out small-RNA sequencing to identify miRNAs expressed in the early gastrula of Xenopus laevis. We identify a total of 180 miRNAs, and we have identified the locations of the miRNA precursor sequences in the X. laevis genome. Of these miRNAs, 141 represent miRs previously identified in Xenopus tropicalis. Alignment to human miRNAs led to the identification of 39 miRNAs that have not previously been described for Xenopus. We have also used a biochemical approach to isolate mRNAs that are associated with the RNA-Induced Silencing Complex (RISC) in early gastrulae and thus candidate targets of miRNA-dependent regulation. Interrogation of this RISC-associated mRNA pool by RT-PCR indicates that a number of genes essential for early patterning and specification may be under regulation by miRNAs. Smad1 transcripts are associated with the RISC; target prediction algorithms identify a single miRNA-binding site for miR-26, which is common to the 3'UTRs of Smad1a and Smad1b. Disruption of the interaction between miR-26 and the Smad1 3'UTR via a Target Protector Morpholino Oligonucleotide (TPMO) leads to a 2-fold increase in Smad1 protein accumulation, moderate increases in the expression of BMP4/Smad1 target genes, and a reduction in organizer gene expression, as well as a partially ventralized phenotype in approximately 25% of embryos. Overexpression of miR-26 resulted in moderately decreased expression of Smad1-dependent genes and an expansion of the region expressing the Organizer gene not1. Our findings indicate that interactions between miR-26 and the Smad1 3'UTR modulate Smad1 function in the establishment of axial patterning; they also establish a foundation for the functional analysis of miRNAs and their regulatory interactions during gastrulation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The mechanisms dictating whether a cell proliferates or differentiates have undergone intense scrutiny, but they remain poorly understood. Here, we report that UPF1, a central component in the nonsense-mediated RNA decay (NMD) pathway, plays a key role in this decision by promoting the proliferative, undifferentiated cell state. UPF1 acts, in part, by destabilizing the NMD substrate encoding the TGF-β inhibitor SMAD7 and stimulating TGF-β signaling. UPF1 also promotes the decay of mRNAs encoding many other proteins that oppose the proliferative, undifferentiated cell state. Neural differentiation is triggered when NMD is downregulated by neurally expressed microRNAs (miRNAs). This UPF1-miRNA circuitry is highly conserved and harbors negative feedback loops that act as a molecular switch. Our results suggest that the NMD pathway collaborates with the TGF-β signaling pathway to lock in the stem-like state, a cellular state that is stably reversed when neural differentiation signals that induce NMD-repressive miRNAs are received., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

FGFs and BMPs act in concert to regulate a wide range of processes in vertebrate development. In most cases, FGFs and BMPs have opposing effects, and specific developmental outcomes arise out of a balance between the two growth factors. We and others have previously demonstrated that signaling pathways activated by FGFs and BMPs interact via inhibitory crosstalk. Here we demonstrate a role for the BMP effector TGF-β Activated Kinase 1 (TAK1) in the maintenance of Smad1 activity in Xenopus embryos, via the inhibition of erk MAPK. Up- or downregulation of TAK1 levels produces an inverse alteration in the amount of activated erk MAPK. The inhibition of erk MAPK by TAK1 is mediated by p38 and a corresponding decrease in phosphorylation of MEK. TAK1 morphant embryos show a decrease in the nuclear accumulation of Smad1. Conversely, reduction of erk MAPK activity via overexpression of MAP Kinase Phosphatase1 (MKP1) leads to an increase in nuclear Smad1. Both TAK1 morphant ectoderm and ectoderm treated with FGF show a decrease in the expression of several Smad1-inducible genes. Neural-specific gene expression is inhibited in isolated ectoderm coexpressing noggin and TAK1, suggesting that TAK1 is sufficient to inhibit neural specification. Introduction of TAK1 morpholino oligonucleotide expands the expression of organizer genes, disrupts formation of the boundary between organizer and non-organizer mesoderm, and increases the spatial range of MAPK activation in response to localized FGF. Our results indicate that inhibitory interactions between FGF and BMP4 effector pathways increase the robustness of BMP signaling via a feed-forward mechanism., (Copyright © 2012 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)