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We developed a protocol for the preparation of valuable 5H-dibenzo[a,d]cycloheptenes by a formal [5 + 2] annulation of ortho-aryl alkynyl benzyl alcohols with arenes. Structurally diverse 5H-dibenzo[a,d]cycloheptenes were achieved in moderate to good yields.

In this paper, we study a free boundary problem for vascularized tumor growth with a time delay in the process of tumor regulating apoptosis. The characteristic of this model is that both vascularization and apoptosis regulation is considered. In mathematical form, this model is expressed as a free boundary problem with Robin boundary. We prove the existence and uniqueness of the global solution and their asymptotic behavior. The effects of vascularization parameters and apoptosis regulation parameters on tumor are discussed. Depending on the importance of regulating the apoptosis rate, the tumor will tend to the unique steady state or eventually disappear. For some parameter values, the final results show that the dynamic behavior of the solutions of our model is analogous to the quasi-stationary solutions. Our results are also verified by numerical simulation.

Background The CRISPR-Cas13 system is an RNA-guided RNA-targeting system and has been widely used in transcriptome engineering with potentially important clinical applications. However, it is still controversial whether Cas13 exhibits collateral activity in mammalian cells. Results Here, we find that knocking down gene expression using RfxCas13d in the adult brain neurons caused death of mice, which may result from the collateral activity of RfxCas13d rather than the loss of target gene function or off-target effects. Mechanistically, we show that RfxCas13d exhibits collateral activity in mammalian cells, which is positively correlated with the abundance of target RNA. The collateral activity of RfxCas13d could cleave 28s rRNA into two fragments, leading to translation attenuation and activation of the ZAKα-JNK/p38-immediate early gene pathway. Conclusions These findings provide new mechanistic insights into the collateral activity of RfxCas13d in mammalian cells and warn that the biosafety of the CRISPR-Cas13 system needs further evaluation before application to clinical treatments.

Next location recommendation aims to mine users’ historical trajectories to predict their potentially preferred locations in the next moment. Although previous studies have explored the idea of incorporating location or social contextual information for recommendation, they still suffer from several major limitations: (1) not fully considering the semantic associations between locations, (2) not considering the heterogeneity in preferences of socially linked users, (3) not fully utilizing contextual information from distinctive sources to further improve the recommendation performance. In this paper, we propose a novel multi-context-based next location recommendation model that incorporates location context, trajectory context, and social context to obtain comprehensive users’ preferences while allowing for interactions between contexts. Specifically, we first develop an efficient method combining both high-order location graphs and location semantic graphs to characterize subtle associations between locations. Then we explore the social contextual information and introduce the location subgraph which considers heterogeneous preferences among friends. Finally, we use the LSTM and geo-dilated LSTM to capture the spatio-temporal associations between users’ trajectories and integrate various contextual information to improve model performance. Extensive experiments on three real datasets show that our model has superior results in the next location recommendation task over other baselines.

A new synthetic methodology for the synthesis of 5

Phosphodiesterase 4 (PDE4), the largest member of PDE family, is highly expressed in mammalian brain. It selectively hydrolyzes the second messenger cyclic adenosine monophosphate (cAMP), a correlate of brain functions including learning, memory and cognitive abilities. Its inhibition is beneficial to counteract cognitive deficits. Thus, targeting PDE4 may be a viable strategy for cognitive improvement. Currently, many PDE4 inhibitors have been discovered but with a great hurdle in clinical development due to adverse effects such as emesis. Analysis of PDE4 subtypes and discovery of subtype specific regulators indicate therapeutic benefits with improved safety in preclinical and clinical models. Herein, we summarize PDE4 structure, describe PDE4 mediated signaling pathways, review the role of individual PDE4 subtypes and discuss the development of PDE4 inhibitors for cognitive improvement, trying to give an insight into the strategy for cognitive improvement with PDE4 inhibitors in future.

BackgroundThis study aimed to present the psychometric properties (dimensionality, reliability, and invariance) of the Chinese 14-Item Resilience Scale (RS-14) within Chinese register nurses (RNs) with less than 3 years work experiences. And we aimed to compare the fit of a unidimensional model and a bifactor model.Materials and methodsThis multicenter cross-sectional survey was conducted from August to September in 2019. A total of 7,231 registered nurses from 90 hospitals were recruited. Data was anonymously obtained through online questionnaires. Both reliability and validity of Chinese RS-14 were assessed. The confirmatory factor analyses (CFA) were used to compare the fit of two different factor structures of the RS-14 (unidimensional model vs. a bifactor model). Moreover, multigroup CFA (MGCFA) were applied to evaluate the measurement invariance (MI) across sociodemographic parameters (gender, educational level, marital status, and et al.).DesignCross-sectional quantitative analyses.ResultsOur study confirmed that the bifactor model presented the best fit within Chinese nurses (CFI = 0.924, TLI = 0.909, RMSEA = 0.095, SRMR = 0.043), and found strong factorial invariance across gender, marital status, and status of receiving standardized training. The reliability of RS-14 was high with a Cronbach’s alpha coefficient of 0.939. Moreover, RS-14 was positively correlated with the social support and was negatively correlated with workplace bullying.ConclusionThis is the first study to explore the latent factor structure for the RS-14 among Chinese RNs and evaluated MI across a series of sociodemographic variables. Based on our findings, the Chinese version RS-14 is both valid and reliable.

A silver nanocluster fluorescent probe was synthesized by using the pyridinium-based ionic liquid [C

The complexity of metabolites in traditional Chinese medicine (TCM) hinders the comprehensive profiling and accurate identification of metabolites. In this study, an approach that integrates enhanced column separation, mass spectrometry post-processing and result verification was proposed and applied in the identification of flavonoids in

Homozygous mutations in Ig-like domain of LMNA cause severe progeria. Unlike typical HGPS mediated by progerin due to LMNAWT/G608G mutation, it remains elusive how these homozygous mutations cause progeria. We here found that patients with LMNAR527C/R527C mutation developed an atypical progeria with autoimmune symptoms. Compare to LMNAWT/G608G mutation, this mutation led to more severe inflammation in patients. MSCs from LMNAR527C/R527C patients exhibited overt inflammation and cellular senescence. Mechanistically, LMNAR527C/R527C mutation attenuated its binding to DNA binding protein BAF, which led to aberrant aggregation of Lamin A and activation of DNA sensing pathways. Inhibition of DNA sensors, cGAS or AIM2, can suppress inflammation and rescue the senescence of patient-derived MSCs. LmnaR527C/R527C mice showed enhanced inflammation, and developed accelerated aging and dead at an early age after high-fat diet (HFD) feeding, which could be rescued by deficiency of AIM2 or treatment by a small molecule inhibitor of cGAS-STING. Therefore, we demonstrated that LMNAR527C/R527C mutation damped its interaction with DNA-binding proteins and exposed damaged DNA to the cytosolic DNA sensors, which triggered aberrant inflammatory responses and promoted the onset of accelerated aging. The present study uncovered that an inflammation driven progeria was caused by LMNA mutation and DNA sensing pathways could be potential therapeutic targets for progeria syndromes caused by homozygous mutations in Ig-like domain of LMNA.

Hypopharyngeal liposarcomas are extremely rare. Due to the lack of experience, pathologists and surgeons find it difficult to make a clear diagnosis and provide accurate, timely treatment. A 43-year-old man with a complaint of foreign body sensation in the throat for 6 months and swallowing difficulty for 2 months was admitted to our department. Contrast-enhanced computed tomography of the chest and larynx revealed a lesion with smooth surface in the esophagus, connected by a pedicle to the hypopharyngeal lesion. The same result was found by gastroscopy. Lateral pharyngotomy was performed for tumor removal, and after 3 weeks, the patient showed good movement of bilateral vocal cords, without dysphagia, choking cough, or hoarseness. This is the first case report of hypopharyngeal liposarcoma invading the esophagus. A thorough preoperative evaluation may be required for the proper diagnosis, prevention, and treatment.

The SABATH family proteins catalyse S-adenosyl-l-methionine-dependent methylation of hormones, signal molecules and other metabolites in plants, and they play an important role in various processes of plant development, especially in plant resistance. Solanum lycopersicum is an important model plant and provides fleshy fruits that are widely used. To date, the SABATH family has not been investigated in Solanum lycopersicum. Here, a total of 20 SABATH amino acid sequences were identified and characterized in S. lycopersicum (SlSABATH). Phylogenetic analysis of different species indicated that these proteins could be classified into 3 groups, and proteins with similar functions were classified into the subclades. Chromosomal mapping showed that SlSABATH proteins were distributed on 7 chromosomes. Conserved domain and motif analysis revealed that these proteins shared homology in 10 motifs, and motifs 2 and 5 were the specific binding sites for S-adenosyl-l-methionine. The structural features of each SlSABATH member showed that those in the same subgroup containing the same exon-intron patterns generally catalysed the same substrate. There were 7 pairs in the SlSABATH family that were produced from the tandem duplication of genes and 2 pairs that were produced during the segmental duplication of genes; these were primary driving forces in the evolution of SlSABATH family. Plant hormone-responsive, stress-inducible and defence-related elements and light-responsive elements accounted for most of the cis regulatory-elements. Gene expression profiling revealed that most of the SlSABATH members were expressed in tissues, Solyc01g080970 was significantly expressed in fully opened flowers and Solyc09g091550 was abundantly expressed in stems. Many SlSABATH genes were significantly up- or downregulated by stress treatments (Pseudomonas syringae pv. tomato DC3000, cold and drought). The above results provide references to further study the function of SlSABATH family members in S. lycopersicum.

The pollen and pistil polygalacturonases in Nicotiana tabacum were identified and found to regulate pollen tube growth and interspecific compatibility. Polygalacturonase (PG) is one of the enzymes catalyzing the hydrolysis of pectin. This process plays important roles in the pollen and pistil. In this research, the pollen and pistil PGs in Nicotiana tabacum (NtPGs) were identified, and their expression, localization and the potential function in the pollen and interspecific stigma incompatibility were explored. The results showed that 118 NtPGs were retrieved from the genome of N. tabacum. The phylogenetic tree and RT-qPCR analysis led to the identification of 10 pollen PGs; among them, two, seven and one showed specifically higher expression levels in the early development of anthers, during pollen maturation and in mature anthers, respectively, indicating their function difference. Immunofluorescence analysis showed that PGs were located in the cytoplasm of (1) mature pollen and (2) in vitro grown pollen tubes, as well as in the wall of in vivo grown pollen tubes. Four NtPGs in clade A were identified as the pistil PGs, and the pistil PGs were not found in clade E. Significantly higher PGs expression was recorded after incompatible pollination in comparison with the compatible stigma, indicating a potential function of PGs in regulating stigma incompatibility. The influence of PGs on pollen tube growth was explored in vitro and partly in vivo, showing that high PGs activity inhibited pollen tube growth. The application of PGs on the otherwise compatible stigma resulted in pollen tube growth inhibition or failure of germination. These results further supported that increased PGs expression in incompatible stigma might be partially responsible for the interspecific stigma incompatibility in Nicotiana.

SummaryThe CRISPR-Cas13 system is an RNA-guided RNA-targeting system, and has been widely used in transcriptome engineering with potentially important clinical applications. However, it is still controversial whether Cas13 exhibits collateral activity in mammalian cells. Here, we found that knocking down gene expression using RfxCas13d in the adult brain neurons caused death of mice, which was not resulted from the loss of target gene function or off-target effects. Mechanistically, we showed that RfxCas13d exhibited collateral activity in mammalian cells, which is positively correlated with the abundance of target RNA. The collateral activity of RfxCas13d could cleave 28s rRNA into two fragments, leading to translation attenuation and activation of the ZAKα-JNK/p38-immediate early gene (IEG) pathway. These results provide new mechanistic insights into the collateral activity of RfxCas13d and warn that the biosafety of CRISPR-Cas13 system needs further evaluation before applying it to clinical treatments.

Emotional bias, which describes human's asymmetric processing of emotional stimuli, consists of negativity bias (Increased response to negative over positive stimuli) and positivity offset (the reversed phenomenon). Previous studies suggest that stimulus arousal (high/low), stimulus type (scenic/verbal), cultural background (Eastern/Western), and task setting (explicit/implicit) may modulate emotional bias, but with inconclusive findings. To address how the profile of emotional bias varies with these factors, a meta-analysis of emotional P3 event-related potential amplitudes was performed. Forty-nine effect sizes from 38 studies involving 1263 subjects were calculated using Hedges'g. The results highlight significant moderators of arousal, stimulus type, and task setting. Specifically, high-arousal stimuli enhance negativity bias relative to low-arousal stimuli; scenic stimulus leads to a negativity bias while verbal stimulus is linked with a positivity offset; explicit emotion tasks lead to negativity bias, whereas implicit emotion tasks do not exhibit emotional bias. These results indicate that emotional bias is labile depending on stimulus arousal, stimulus type and task setting. The implication of these findings for emotion regulation is discussed.

The importance to clarify the drug metabolites is beyond doubt in view of their potential efficacy and safety. However, due to the complex matrix interference, relatively low content and the co-eluting effect, it is of a great challenge to comprehensively and systematically characterize the metabolites in vivo, especially for the traditional Chinese medicines (TCMs) due to the numerous types of components. In the present study, a comprehensive off-line two-dimensional separation system combining with data independent acquisition (DIA) mode and multi-dimensional data deconvolution method was established for chromatographic separation, data acquisition and data procession of indole alkaloids in rat plasma after intragastrically administrated with the extract of Uncaria rhynchophylla at the dose of 1 g/kg. The orthogonality of the off-line 2D separation system consisting of HILIC for first-dimensional separation and the PRLC for second-dimensional separation was valuated with the “asterisk” equations, and the results showed that off-line 2D separation system had passable orthogonality (A0 = 53.3%). Furthermore, the DIA mode was applied to capture MS/MS spectra in view of its advantage in acquiring MS data, and an effective multi-dimensional deconvolution method integrating the calculation of chemical formula, the extraction of diagnostic ion, the filter of ring double bond (RDB) and the judgement of neutral loss was established to parse the spectra for the complicated DIA data for comprehensive analysis of metabolites in rat plasma. Ultimately, a total of 127 indole alkaloids were tentatively characterized, and the main metabolic pathways were inferred as demethylation, dehydrogenation, hydroxylation and deglycosylation. The off-line two-dimensional separation system was applied for the comprehensive characterization of metabolites in vivo for the first time. This study suggested a new approach to enable the enrichment, separation and analysis of the low content components in vivo.

Cardiac pressure overload is a crucial risk factor for cardiac hypertrophy and heart failure. Our previous study showed that depletion of the β3-adrenergic receptor (ADRB3) induced left ventricular diastolic dysfunction via potential regulation of energy metabolism and cardiac contraction. However, the effects of ADRB3 on pressure overload-induced heart failure remain unclear. In the present study, systemic ADRB3-knockout mice suffering from transverse aortic constriction (TAC) surgery were used to identify the effects of ADRB3 on pressure overload-induced heart failure. Compared to wild-type mice, ADRB3 depletion significantly improved the left ventricular ejection fraction, reduced left ventricular posterior wall thickness and interventricular septum thickness, and decreased the area of cardiomyocytes after TAC. RNA sequencing and bioinformatics analysis showed that ADRB3 depletion up-regulated 275 mRNAs and down-regulated 105 mRNAs in mice suffering TAC surgery. GO analysis, GO-tree analysis, and GSEA showed that ADRB3 depletion mainly enhanced the innate immune response of hearts in cardiac pressure overload mice. In addition, pathway analysis and Pathway-Act analysis presented that innate immune response-related pathways, including RIG-I-like receptor signaling pathway, antigen processing and presentation, Toll-like receptor signaling pathway, and cell adhesion molecules, were significantly enriched in ADRB3-KO-TAC mice. Ten hub genes were identified using protein-protein interaction network, MCODE, and cytoHubba analysis. Furthermore, the depletion and activation of ADRB3 validated the effects of ADRB3 on the innate immune response of hearts after TAC. In conclusion, ADRB3 depletion relieves pressure overload-induced cardiac hypertrophy and heart failure, and these effects could be explained by the enhancement of innate immune response.

Steam-assisted gravity drainage (SAGD) is an important method of heavy oil production, and the solvent vapor extraction (VAPEX) process is also an economically feasible, technically reliable, and environmentally friendly in situ heavy oil recovery method. In this paper, a microscopic visual flooding device was used to conduct seven groups of visual flooding experiments, including hot water, steam, liquid solvent and vapor solvent, at different temperatures. It can be directly observed that the residual oil in the hot water swept area is generally distributed in “spots”, “strips” and “clusters” of varying sizes. The residual oil after steam flooding generally has a “cluster” distribution, the residual oil after liquid solvent flooding has a “film” distribution, and there is only a little “spot” residual oil distributed after solvent vapor flooding. Additionally, we found that the sweep efficiency and displacement efficiency of hot water, steam and solvent increase with increasing temperature, and the sweep efficiency of hot water is higher than that of steam and liquid solvent. Vapor solvent has the greatest recovery factor, reaching approximately 90%. The experimental results hint at the future development trend of solvent injection and support the foundation of more general applications pertaining to the sustainable production of unconventional petroleum resources.

In this paper we consider a free boundary problem modeling tumor growth with angiogenesis. The model is a free boundary problem of a system of partial differential equations. With Robin boundary, the model contains an ordinary differential equation describing the radius of tumor cell and two parabolic equations describing the evolution of nutrient concentration and inhibitor concentration, respectively. We study the number of the stationary solution of above problem, the existence and uniqueness of local solution and global solution, and the asymptotic behavior of the solution.

In this paper we study a granuloma model in visceral leishmaniasis, which contains eleven coupled reaction diffusion equations. The existence and uniqueness of the model in the local solution is proved by using the Banach Fixed Point Theorem and theory of parabolic equation. Then, the existence and uniqueness of the global solution are obtained by using the extension method.

Purpose:To verify the psychometrical properties of the Chinese-version VEnous INsufficiency Epidemiological and Economic Study-Quality of Life/Symptoms (VEINES-QOL/Sym) questionnaire, in Chinese patients with deep venous thrombosis.Methods:The English-version VEINES-QOL/Sym questionnaire was translated into Chinese by forward-translation, back-translation and cultural adjustment, and approved by the original authors. It was administered to patients with deep venous thrombosis of the two local hospitals in Nanchong from Jul 2017 to Jan 2018. The internal consistency reliability and construct validity of the Chinese version of VEINES-QOL/Sym questionnaire were evaluated. Main outcome measures were as follows: Reliability was tested using Cronbach’s alpha coefficient, internal consistency reliability, retest reliability, split-half reliability . Validity was verified by structure validity, content validity and criterion-related validity.Results:In pilot study, a total of 132 participates completed the questionnaire. In validity sample, a total of 335 participates completed the questionnaire. The Chinese-version VEINES-QOL/Sym questionnaire has 25 items. And it had good internal consistency and stability (Cronbach’s α coefficients ranging from 0.877-0.930, split-half coefficients ranging from 0.792-0.913 and retest coefficients ranging from 0.891-0.987). The Chinese-version VEINES-QOL/Sym summary score had good criterion-related validity in the PCS (physical component summary) and MCS (mental component summary) of Chinese-version SF-36 (0.801 and 0.792). Four factors emerged from exploratory factor analysis, which named symptoms (Q1a-i, Q6), physical functioning (Q2, Q3a-d), role-physical (Q4a-d, Q5) and mental health (Q7a-e) respectively. ConclusionsThis questionnaire was shown to be reliable and valid in the Chinese language. We propose that the Chinese-version VEINES-QOL/Sym is a useful tool for local use.

In this paper, we study the parabolic–hyperbolic system about the growth of a tumor. The model is a coupled system of PDEs with Robin boundary, which involves nutrient density, extracellular matrix and matrix degrading enzyme. By transforming the free boundary into a fixed boundary and using strict mathematical analysis, we can prove the existence and uniqueness of the radially symmetric stationary solution. By the fixed point theorem, we obtain the existence and uniqueness of the radially symmetric solution globally in time.

Nicotiana alata is a model species used to study gametophytic self-incompatibility (SI), controlled by the S-locus (encoding S-RNase and SLF proteins expressed in pistil and pollen, respectively) as well as by modifier genes (such as 120 kDa, HT-b and Trxh). A previous study revealed that SI in N. alata accession S2S2 was plastic, and that SI was leaky with senescence of the pistil and plant. Here, we further explored its regulatory mechanisms. Reverse transcription quantitative PCR (RT-qPCR) and western blot results showed that during the senescence of pistil in S2S2, 120 kDa and HT-b were transcribed and translated at lower levels, while marked residual S-RNase activity was detected. The transcripts of Trxh varied irregularly. Only the transcription and translation of 120 kDa declined with the plant senescence. According to the results, PSF in S2S2 may be associated with down-regulated expression of 120 kDa and HT-b, while S-RNase and Trxh seem to be unrelated to this phenotype. These findings deepen our understanding of the regulatory mechanisms of SI plasticity in N. alata.

China has grown into the fastest growing and most dynamic emerging express delivery market in the world. The paper puts forward a PLS_SEM method to calculate the customer satisfaction of the express delivery companies. Through an investigation in 50 cities, the authors conclude that company’s brand and service quality are key influence factors in consumer satisfaction. Company CC gets the best customer satisfaction, while BB and FF get the lowest result. Customers prefer the product integrity, ease of ordering, overall image and scope of delivery. They give the worst experience in the service characteristics.

Nowadays, civil aviation is an important industry in national economic and social development, and also an advanced means of transportation. The competition among airlines is becoming increasingly fierce. The paper puts forward a PLS_SEM method to evaluate the customer satisfaction. Through an investigation in 50 cities, the authors conclude that customer cares more on the brand and service quality. Company EE gets the highest customer satisfaction and BB gets the lowest result. Customers prefer the cabin crew, overall image, website and APP, and the ground information disclosure accuracy. They give the worst experience in the catering situation.

BACKGROUND The aim of this study was to understand the changes in psychological factors and sleep status of front-line medical staff in the fight against COVID-19 and provide evidence of exercise interventions to relieve psychological stress and improve sleep status for medical staff. MATERIAL AND METHODS A survey study was conducted among 120 front-line medical staff in the fight against COVID-19, of which 60 medical staff worked at the designated hospital (experimental group) and 60 medical staff worked at the non-designated hospital (control group). The Symptom Checklist 90 (SCL-90), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and PTSD Checklist-Civilian Version (PCL-C) were used to assess mental status. Sleep status was assessed using the Pittsburgh Sleep Quality Index (PSQI). RESULTS SCL-90 scores of somatization, depression, anxiety, and terror were higher than normal in front-line medical staff at the designated hospital. The SAS (45.89±1.117), SDS (50.13±1.813), and PCL-C (50.13±1.813) scores in the experimental group were higher than the normal control group, and were significantly different from those in the control group on SDS and PCL-C scales (P

Nowadays, service industry represents the main engine of China’s economic development. By using the structural equation model (SEM), we can identify the influence coefficient of different factors of consumer satisfaction, which can help to better promote high-quality development of service industry. In this paper, we find that consumers pay more attention on brand image and perceived quality and care less about expected quality and perceived value of our survey of six service industries, which are express delivery, express hotel, aviation, auto insurance, online travel and mobile communication. The results suggest that we can promote the quality development of service industry by strengthening brand building, enhance brand characteristics and individuality, and improve customer perceptions of different dimensions of service industry, such as service environment, service personnel, service personalization and service professionalism.

The SARS-CoV-2 pandemic poses an unprecedented public health crisis. Accumulating evidences suggest that SARS-CoV-2 infection causes dysregulation of immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced by SARS-CoV-2 in animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could reduce inflammatory response and rescue the pneumonia with substantial reduction of viral titers in SASR-CoV-2 infected animals. Remarkably, Paquinimod treatment resulted in 100% survival of mice in a lethal model of mouse coronavirus (MHV) infection. A novel group of neutrophils that contributed to the uncontrolled inflammation and onset of COVID-19 were dramatically induced by coronavirus infections. Paquinimod treatment could reduce these neutrophils and regain antiviral responses, unveiling key roles of S100A8/A9 and noncanonical neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention. Funding: This work was supported by the National Natural Science Foundation of China (31570891; 31872736), the National Key Research and Development Program of China (2016YFA0500302; 2020YFA0707800), the National Key Research and Development Program (2020YFA0707500) and the Strategic Priority Research Program (XDB29010000). Xiangxi Wang was supported by Ten Thousand Talent Program and the NSFS Innovative Research Group (81921005). We thank National Mega projects of China for Major Infectious Diseases (2017ZX10304402), CAMS initiative for Innovative Medicine of China (2016-12M-2-006) and The National Natural Science Foundation of China (82041008) for the support on the animal model study. Conflict of Interest: The authors have no conflicts of interest to declare. Ethical Approval: All experiments with live SARS-CoV-2 viruses were carried out in the enhanced biosafety level 3 (P3+) facilities in the Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) approved by the National Health Commission of the People’s Republic of China. All animals care and use were in accordance with the Guide for the Care and Use of Laboratory Animals of the Chinese Association for Laboratory Animal Science. All procedures of animal handling were approved by the Animal Care Committee of Peking University Health Science Center.

The wide scope of service industry is directly related to the growing needs of people’s better life and to the formation of a strong domestic market. Study of the quality of service industry would help to improve the pertinence of service supervision and further promote service quality improvement. By building an evaluation model of customer satisfaction in service industry, we can calculate customer satisfaction in different service industry and identify factors that influence customer satisfaction most. In addition, we expand the service quality analysis dimension by including service trade, service complaints, service certification and service brand in the article. From the results, it is clearly to be seen that China’s service industry quality has remained relatively satisfactory, and there have a gradual improvement in service trade, service complaints and service management.

Supplemental material, sj-pdf-1-imr-10.1177_0300060520952276 for Ramsay Hunt syndrome affecting the vagus nerve with epiglottic ulcers as the first manifestation: a case report by Jie Zhang and Xuemei Wei in Journal of International Medical Research

mRNA m6A modification is involved in modulation of immune responses. However, its function in antiviral immunity is controversial, and how immune responses regulate m6A modification remains unknown. We here found TBK1, a key kinase of antiviral pathways, phosphorylated the core m6A methyltransferase METTL3 at Serine 67. The phosphorylated METTL3 interacted with translational complex to enhance proteins translation, including IRF3, thus facilitating antiviral responses. TBK1 also promoted METTL3 activation and m6A modification, which was required for stabilizing IRF3 mRNA. Type I IFN induction was severely impaired in METTL3 deficient cells. Mettl3fl/fl-lyz2-Cre mice were more susceptible to IAV-induced lethality than control mice. Consistently, Ythdf1—/— mice showed higher mortality than wild type mice due to decreased IRF3 expression and subsequently attenuated IFNs production. Together, we demonstrated that innate signals activated METTL3 via TBK1, then METTL3 mediated m6A modification secured antiviral immunity by promoting mRNA stability and protein translation.

BACKGROUND Measles morbidity and mortality were significantly reduced after the measles vaccine was introduced in China in 1965. However, measles outbreaks easily occur in densely populated areas, especially where there is no universal vaccination. The outbreak that occurred in Shenzhen, the Chinese city with the largest internal immigration, provides a lesson in measles virus mutation and measles prevention. The present study is a phylogenetic analysis of measles viruses and comparison of clinical signs between individuals with and without vaccination. MATERIAL AND METHODS We performed phylogenetic analysis of the nucleoprotein (N) genes of measles virus from 129 measles patients in Shenzhen from January 2015 to July 2019. Phylogenetic trees were constructed using the neighbor-joining method. RESULTS The phylogenetic analysis showed all viruses were classified into genotype H1. In addition, there is often a seasonal measles outbreak in July each year. The clinical data showed that patients who were unvaccinated were more likely to have coughing, chronic bronchitis, conjunctivitis, catarrh, Koplik spots, and diarrhea. Children of migrant workers and those living in mountainous and rural districts accounted for most measles cases. CONCLUSIONS Our results showed there was a seasonal measles outbreak in Shenzhen Children's Hospital. All the measles virus from 129 measles patients were H1 viruses. The clinical signs also showed a difference between unvaccinated and vaccinated patients. Moreover, most of the unvaccinated patients came from migrant worker families. We suggest there is a need for increased health promotion and vaccination programs for migrant workers and people living in remote villages.

BACKGROUND Physical education (PE) is part of the curriculum in Chinese universities. The psychological burden, or anxiety levels, for students in PE classes, can result from several factors, including teaching content, teaching environment, and the organization of the teaching methods. The aim of this study was to assess the psychological burden on students in PE classes in Chinese universities. MATERIAL AND METHODS The study included 400 students (200 men and 200 women) from a Chinese university, who participated in PE classes. The distribution of the levels of psychological burden associated with PE was assessed using subjective measurements and a fuzzy comprehensive evaluation method that to provide an integrated framework combining the results of judgments made at multiple stages of the evaluation process. RESULTS Of the 400 study participants who attended PE classes, 61.5% of male students and 47.5% of female students coped well or very well when dealing with the perceived psychological burden; 33.5% of male students and 42.5% of female students reported a medium level of psychological burden. Few students reported a high level of psychological burden associated with PE classes. The average psychological burden in female students was greater than for male students who participated in PE classes. CONCLUSIONS The combination of subjective measurement of the psychological burden associated with PE classes by university students in China, combined with a fuzzy comprehensive evaluation method showed that female university students might require more support than male students to overcome any psychological burden associated with PE classes.

This paper presents a new comprehensive approach to model High Energy Gas Fracturing (HEGF) process. This coupled model consists of 6 sub-quantitative modules, including (1) loading build-up due to propellant deflagration, (2) gas-liquid interface displacement caused by killing liquid column movement, (3) stress distribution around the casing wellbore and the perforation holes, (4) fluid penetration through the perforation holes, (5) rate dependent critical pressure of fracture initiation and (6) hydro-mechanical coupled fracture propagation. The solution to the coupled model is obtained combining the analytical method and finite difference method, which solves the mass conservation equation and energy conservation equation with the subsystem pressure and temperature as the main variables. Subsequently, The single pulse and the multi-pulse HEGF processes are simulated. The dynamic changes of the loading built-up of propellant deflagration, the movement of killing liquid column as well as the dynamic propagation of fracture are further studied. Meanwhile, in-depth analysis has been applied on the affect sensitivity of the five key parameters to the single pulse HEGF results as well as the mechanism of multi-pulse HEGF. The results indicate that the final lengths of fractures generated by single pulse HEGF can be extended with the increase of the perforation density, the diameter of perforation holes, the thickness of propellant column and the total propellant quality. However, the effect of the height of killing liquid column is insignificant. It also demonstrates that the multi-pulse HEGF could bring multiplier fractures length by concatenating series propellants with different burning rates. This coupled model could add new dimensions to the understanding of the coupled mechanism of single pulse and multi-pulse HEGF. In addition, the model could be applied as a parameters quantitative design tool to assist the field implementation of these technologies.

This paper is devoted to the existence and Lipschitz continuity of global conservative weak solutions in time for the modified two-component Camassa–Holm system on the real line. We obtain the global weak solutions via a coordinate transformation into the Lagrangian coordinates. The key ingredients in our analysis are the energy density given by the positive Radon measure and the proposed new distance functions as well.