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In task-based second language (L2) writing research, genre effects on linguistic features are usually explained by either task complexity hypothesis or differences in communicative demands. The basic distinction between the two explanations is determined by whether cognitive factors are at work. To date, the actual causes for L2 learners' different linguistic features in different genres are still unclear. Aiming at providing empirical evidence for explaining the mechanism of genre effects, this investigation uses dependency-grammar-based measures to examine the role of cognitive factors in L2 argumentative, narrative, and descriptive writings. A total of 540 compositions from three different proficiency groups of English as a foreign language learners were collected, and their mean dependency distances and their distributions of dependency distance were calculated. It was found that in all proficiency groups of compositions, dependency distance distributions of five types showed significant differences between genres. Since dependency distance reflects cognitive load, those five dependency types were able to show that cognitive factors are at play in the writing process. Among the five types, the phrasal dependency relation types could reveal genre effects regardless of learners' language proficiency, and clausal dependency relation types might pinpoint learners' threshold of perceiving task complexity. The findings suggest that genre effects on linguistic features in L2 writings may result from different cognitive demand imposed by writing tasks with different genres, and genre effect may exhibit variation among different proficiency groups.

Well-defined key competencies for students with autism spectrum disorders (ASD) help develop curriculum and pedagogies that emphasize what students with ASD are expected to learn, to know and to do. Most of the current research on the key competencies of ASD is theoretical and based on the social and cultural backgrounds of western countries. The key competencies defined by most of the research lack of the support of empirical evidence. This study sought to identify the key competencies of school-age students with ASD from the perspectives of teachers and parents. Based on the review of existing key competencies frameworks, a key competencies instrument that consisted of 76 learning outcome items in eight domain areas was developed. An online survey to explore the teachers’ and parents’ views of the key competencies was conducted with 1,618 teachers and 2,430 parents of students with ASD across China. The results showed that teachers believed that the key competencies should consist of eight domain areas including social-communication, learning skills, healthy living, play, motor, emotion, sensory processing, and cognition, while the cognition related competencies were not recognized by parents. The competencies in social-communication, learning skills, healthy living had higher variance contribution. From the perspective of teachers, the variance contribution of social communication was the highest, while from the perspective of parents, the variance contribution of learning skills was the largest. Taken together, the key competencies framework for students with ASD should include eight dimensions and 75 learning outcome items. The similarities and differences between the perspectives of the two group were discussed. The findings could provide empirical data to assist in developing educational guidelines and guide the development of models of support for students with ASD.

Lupus nephritis (LN) is a severe renal disease caused by the massive deposition of the immune complexes (ICs) in renal tissue, acting as one of the significant organ manifestations of systemic lupus erythematosus (SLE) and a substantial cause of death in clinical patients. As mesangium is one of the primary sites for IC deposition, mesangial cells (MCs) constantly undergo severe damage, resulting in excessive proliferation and increased extracellular matrix (ECM) production. In addition to playing a role in organizational structure, MCs are closely related to in situ immunomodulation by phagocytosis, antigen-presenting function, and inflammatory effects, aberrantly participating in the tissue-resident immune responses and leading to immune-mediated renal lesions. Notably, such renal-resident immune responses drive a second wave of MC damage, accelerating the development of LN. This review summarized the damage mechanisms and the in situ immune regulation of MCs in LN, facilitating the current drug research for exploring clinical treatment strategies.

IntroductionGlucosamine, the intermediate metabolite of the hexosamine biosynthesis pathway (HBP), is widely used as a supplementary drug in patients with osteoarthritis. However, its consequences in such patients concomitantly suffering from diabetic nephropathy is unknown.MethodsThe aim of the study was to investigate the effect of exogenous administration of glucosamine in the diabetic kidney. A mouse model of streptozotocin-induced diabetic nephropathy in vivo and cultured endothelial cells in vitro were used in the study. The mice were treated with glucosamine for 6 months. Renal function was evaluated by metabolic cage, and histology of the kidney was estimated by periodic acid-schiff (PAS) staining. The expression of related genes was assessed by real-time PCR, immunofluorescence staining, immunoblotting and ELISA.ResultsThere was no significant difference in urinary albumin secretion, relative kidney weight, or creatinine clearance between the groups treated with glucosamine and controls. Assessment of the kidney demonstrated reduction in mesangial expansion and fibronectin expression in the diabetic glomeruli treated with glucosamine. Glucosamine treatment significantly decreased α-smooth muscle actin (α-SMA) protein expression in both diabetic and control kidneys, whereas the expression of other fibrosis-related genes and inflammatory factors was unaltered. Moreover, α-SMA colocalized with the endothelial marker CD31 in the diabetic and control kidneys, and glucosamine reduced α-SMA+ ECs in the diabetic glomeruli. In addition, glucosamine suppressed α-SMA expression in endothelial cells treated with or without high glucose.DiscussionIn summary, this is the first report to show that glucosamine reduces mesangial expansion and inhibits endothelial-mesenchymal transition in diabetic nephropathy. The underlying mechanisms need to be further investigated.

Lettuce (Lactuca sativa L.), which belongs to the large Asteraceae (Compositae) family, breeds by sexual reproduction and produces seeds. Actually, lettuce seeds are achenes, which are defined as fruits. However, few studies have described the morphological characteristics of the lettuce achenes, and genes essential for achene development are largely unknown in lettuce. To investigate the gene activity during achene development and determine the possible mechanisms that influence achene development in lettuce, we performed a time-course transcriptome analysis of lettuce achenes. A total of 27,390 expressed genes were detected at the five achene development stages. We investigated the gene expression patterns during achene development and identified the enriched biological processes at the corresponding stages. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed a variety of transcriptomic similarities and differences at different achene development stages. Further, transcription factors and phytohormones were found to play important roles during achene development. Finally, we proposed a working model to illustrate the gene expression modules and possible molecular mechanisms underlying achene development. Our time-course transcriptome data also provide a foundation for future functional studies to reveal the genetic control of achene development in lettuce.

Single-cell technologies are revolutionizing the entire field of biology. The large volumes of data generated by single-cell technologies are high dimensional, sparse, and heterogeneous and have complicated dependency structures, making analyses using conventional machine learning approaches challenging and impractical. In tackling these challenges, deep learning often demonstrates superior performance compared to traditional machine learning methods. In this work, we give a comprehensive survey on deep learning in single-cell analysis. We first introduce background on single-cell technologies and their development, as well as fundamental concepts of deep learning including the most popular deep architectures. We present an overview of the single-cell analytic pipeline pursued in research applications while noting divergences due to data sources or specific applications. We then review seven popular tasks spanning different stages of the single-cell analysis pipeline, including multimodal integration, imputation, clustering, spatial domain identification, cell-type deconvolution, cell segmentation, and cell-type annotation. Under each task, we describe the most recent developments in classical and deep learning methods and discuss their advantages and disadvantages. Deep learning tools and benchmark datasets are also summarized for each task. Finally, we discuss the future directions and the most recent challenges. This survey will serve as a reference for biologists and computer scientists, encouraging collaborations. [ABSTRACT FROM AUTHOR]

With the rise in piano teaching in recent years, many people have joined the ranks of piano learners. However, the high cost of traditional manual instruction and the exclusive one-on-one teaching model have made learning the piano an extravagant endeavor. Most existing approaches, based on the audio modality, aim to evaluate piano players’ skills. Unfortunately, these methods overlook the information contained in videos, resulting in a one-sided and simplistic evaluation of the piano player’s skills. More recently, multimodal-based methods have been proposed to assess the skill level of piano players by using both video and audio information. However, existing multimodal approaches use shallow networks to extract video and audio features, which limits their ability to extract complex spatio-temporal and time-frequency characteristics from piano performances. Furthermore, the fingering and pitch-rhythm information of the piano performance is embedded within the spatio-temporal and time-frequency features, respectively. Therefore, we propose a ResNet-based audio-visual fusion model that is able to extract both the visual features of the player’s finger movement track and the auditory features, including pitch and rhythm. The joint features are then obtained through the feature fusion technique by capturing the correlation and complementary information between video and audio, enabling a comprehensive and accurate evaluation of the player’s skill level. Moreover, the proposed model can extract complex temporal and frequency features from piano performances. Firstly, ResNet18-3D is used as the backbone network for our visual branch, allowing us to extract feature information from the video data. Then, we utilize ResNet18-2D as the backbone network for the aural branch to extract feature information from the audio data. The extracted video features are then fused with the audio features, generating multimodal features for the final piano skill evaluation. The experimental results on the PISA dataset show that our proposed audio-visual fusion model, with a validation accuracy of 70.80% and an average training time of 74.02 s, outperforms the baseline model in terms of performance and operational efficiency. Furthermore, we explore the impact of different layers of ResNet on the model’s performance. In general, the model achieves optimal performance when the ratio of video features to audio features is balanced. However, the best performance achieved is 68.70% when the ratio differs significantly.

Electrocatalytic reduction of carbon dioxide (CO2RR) employs electricity to store renewable energy in the form of reduction products. The activity and selectivity of the reaction depend on the inherent properties of electrode materials. Single-atom alloys (SAAs) exhibit high atomic utilization efficiency and unique catalytic activity, making them promising alternatives to precious metal catalysts. In this study, density functional theory (DFT) was employed to predict stability and high catalytic activity of Cu/Zn (101) and Pd/Zn (101) catalysts in the electrochemical environment at the single-atom reaction site. The mechanism of C2 products (glyoxal, acetaldehyde, ethylene, and ethane) produced by electrochemical reduction on the surface was elucidated. The C-C coupling process occurs through the CO dimerization mechanism, and the formation of the *CHOCO intermediate proves beneficial, as it inhibits both HER and CO protonation. Furthermore, the synergistic effect between single atoms and Zn results in a distinct adsorption behavior of intermediates compared to traditional metals, giving SAAs unique selectivity towards the C2 mechanism. At lower voltages, the Zn (101) single-atom alloy demonstrates the most advantageous performance in generating ethane on the surface, while acetaldehyde and ethylene exhibit significant certain potential. These findings establish a theoretical foundation for the design of more efficient and selective carbon dioxide catalysts.

ABSTRACT: Subgroup K avian leukosis virus (ALV-K) is a new subgroup of avian leukosis virus (ALV) first identified in Chinese indigenous chickens in recent years. In this study, an ALV-K strain was isolated from Luhua chicken in Shandong province, China, and designated SD20LH01. The full-length genomic sequence of SD20LH01 was 7491 bp, which had the highest homology with ALV-K reference strains GDFX0601, GDFX0602 and GDFX0603. The nucleotide homology of env gene of SD20LH01 with reference strains of subgroup A, B, C, D, E, and J was ranged from 57.1 to 93.2%, while 94.1 to 99.4% with other ALV-K reference strains. The nucleotide difference of SD20LH01 mainly clustered with gp85 gene and U3 sequence when compared with the reference strain of ALV-K. In order to investigate the pathogenicity of SD20LH01, SPF chicken embryos were infected by yolk sac inoculation, and 1-day-old chickens were infected by intraperitoneal inoculation of SD20LH01. The results showed that yolk sac inoculation of SD20LH01 could induce persistent viremia, growth retardation and reduce the immune response to NDV and AIV-H9 vaccines. However, intraperitoneal inoculation in 1-day-old chickens could only induce a low level of viremia. In addition, no tumors were found in infected chickens during the animal experiments. This study enriched the genomic sequence data of ALV-K isolated in Chinese indigenous chickens, and laid a foundation for further study on the pathogenesis and prevention of ALV-K.

PurposePrevious studies on monocular blindness (MB) have mainly focused on concept and impact. The present study measured spontaneous brain activity in MB patients using the percentage of amplitude fluctuation (PerAF) method.MethodsTwenty-nine patients with MB (21 male and 8 female) and 29 age-, gender-, and weight-matched healthy controls (HCs) were recruited. All participants underwent resting state functional magnetic resonance imaging (rs-fMRI). The PerAF method was used to analyze the data and evaluate the spontaneous regional brain activity. The ability of PerAF values to distinguish patients with MB from HCs was analyzed using receiver operating characteristic (ROC) curves, and correlation analysis was used to assess the relationship between PerAF values of brain regions and the Hospital Anxiety and Depression Scale (HADS) scores.ResultsPerAF values in Occipital_Mid_L/Occipital_Mid_R/Cingulum_ Mid_L were significantly lower in patients with MB than in controls. Conversely, values in the Frontal_Sup_Orb_L/Frontal_Inf_Orb_L/Temporal _Inf_L/Frontal_Inf_Oper_L were significantly higher in MB patients than in HCs. And the AUC of ROC curves were follows: 0.904, (p < 0.0001; 95%CI: 0.830–0.978) for Frontal_Sup_Orb_L/Frontal_Inf_Orb_L; Temporal_Inf_L 0.883, (p < 0.0001; 95% CI: 0.794–0.972); Frontal_Inf_Oper_L 0.964, (p < 0.0001; 95% CI: 0.924–1.000), and 0.893 (p < 0.0001; 95% CI: 0.812–0.973) for Occipital_Mid_L; Occipital_Mid_R 0.887, (p < 0.0001; 95% CI: 0.802–0.971); Cingulum_Mid_L 0.855, (p < 0.0001; 95% CI: 0.750–0.960).ConclusionThe results of our study show abnormal activity in some brain regions in patients with MB, indicating that these patients may be at risk of disorder related to these brain regions. These results may reflect the neuropathological mechanisms of MB and facilitate early MB diagnoses.

Abstract: Assessing ecosystem service (ES) balance and exploring critical drivers are crucial for landscape management. However, a lack of understanding of the determinants of the ecosystem service supply–demand budget, their spillover effects, and spatial variabilities offsets the efficacy of landscape planning and ecosystem conservation. This novel study attempted to close this gap by quantifying ecosystem service budget using an expert knowledge-based supply–demand matrix and explored its dependencies through spatial econometrics and geographically weighted regression approaches instead of using ordinary model simulation and conventional statistical analysis. The overall patterns of ecosystem service balance in the southeastern coast were found to have remained stable in 1980, 2000, and 2017, although remarkable ecosystem service deficits were identified in hotspots of rapid urbanization. The ecosystem service balance was negatively associated with the proportions of built-up land and cropland (p < 0.0001) and exhibited positive associations with the proportions of woodland and grassland (p < 0.0001). Landscape structure and population density were identified as the primary determinants of ecosystem service balance and exhibited spatial variability and spillover effects (i.e., determining ecosystem service balance in both individual and adjacent units). These findings demonstrate the significance of spatial disparities and external effects of determinants of the supply–demand budget in integrative landscape governance. Consequently, localized and targeted strategies for landscape planning are increasingly needed to optimize landscape configuration and alleviate ecosystem service imbalance according to individual socioeconomic conditions and landscape structures. In addition, the spillover effects demonstrate that the maintenance of regional ecosystem service balance and ecosystem sustainability depends not only on individual areas but also on cross-regional collaborations with neighboring regions. These findings have critical implications on strategy formulation for coastal landscape management and ecosystem sustainability.

Connectivity, the exchange of individuals and genes among geographically separated marine populations, plays a key role in coral reef biodiversity and resilience. The Red Sea is a semi-enclosed basin with dynamic circulation and abundant coral reefs, making it a natural laboratory for coral reef connectivity research. Previous studies broadly investigated Red Sea connectivity, but were spatially restricted to regional or sparsely-distributed reef sites. Here, using hydrodynamic and particle tracking models, a high-resolution circulation-driven physical connectivity atlas covering every Red Sea coral reef, including seasonality, was simulated and further validated against available in-situ genetic datasets. The simulation was conducted without incorporating larval traits to isolate and quantify the connectivity contributed by circulation. Our validation experiment suggests the importance of circulation in shaping the genetic structure of Red Sea reef species, supporting the Isolation By Circulation (IBC) theory in the Red Sea seascape genetics. The simulated atlas reveals that reefs in the northern Red Sea are better sources and destinations than those in the southern basin, regardless of season. The east-west connections between the southern reefs are identified to be weak. Complex circulation dynamics drive a regional-specific seasonality, e.g., the Farasan Islands reefs are better sources during summer while the nearby Bab-Al-Mandeb strait reefs are better sources during winter. The west-coast reefs are generally winter-intensified sources whereas the east-coast reefs are generally summer-intensified sources. The revealed seasonality of physical connectivity is important for larval dispersal processes as reef species may spawn in different seasons. This physical connectivity atlas provides a reference for designing marine conservation strategies from a circulation perspective and easy-to-access physical connectivity datasets for the future Red Sea seascape genetic studies.

Objective: Lung cancer is a common malignant tumor characterized by challenging detection and lack of specificity in clinical manifestations. To investigate the correlation of tumor markers in the serum with liver metastasis and prognosis of lung cancer.Methods: A total of 3,046 elderly lung cancer patients were retrospectively studied between September 1999 and July 2020. Divided into liver metastasis group and non-liver metastasis group. We compared a series of serum biomarkers between the two groups of elderly patients to predict the prognosis in patients with lung cancer by fluorescence in situ hybridization (FISH), advanced flow cytometry (FCM) and multi tumor marker protein chip, including tumor markers in the serum included alkaline phosphatase (ALP), serum calcium, hemoglobin (HB), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin fragment 19 (Cyfra21-1), carbohydrate antigen-125 (CA-125), carbohydrate antigen-153 (CA-153), carbohydrate antigen-199 (CA-199), and free prostate specific antigen (free PSA). We used binary logistic regression analysis to determine risk factors, and used receiver operating curve (ROC) analysis to evaluate the diagnostic value of liver metastases in elderly patients with lung cancer.Results: The proportion of lung cancer in the liver metastasis group was higher than that observed in the non-liver metastases group. The expression levels of CA-125, Cyfra21-1, and NSE in the liver metastasis group of lung cancer were significantly higher than those reported in the non-liver metastases group (p < 0.05). ROC curve analysis shows that the area under the curve of CA-125, Cyfra21-1, and NSE are 0.614, 0.616 and 0.608, respectively. The sensitivity and specificity of CA-125 were 45.70% and 76.20%, the sensitivity and specificity of Cyfra21-1 were 60.10% and 57.10%, and the sensitivity and specificity of NSE were 44.10% and 75.00%, respectively.Conclusion: High levels of CA-125, Cyfra21-1, and NSE in the serum may be associated with liver metastasis in elderly patients with lung cancer. CA-125 and NSE are factors influencing the prognosis of elderly patients with liver metastasis of lung cancer.

Chicken infectious anemia virus (CIAV) can be transmitted through contaminated live poultry vaccine. However, the pathogenicity of contaminated CIAV strains is rarely reported. Previously, the chickens showed the typical symptoms of anemia after using the attenuated live fowl pox virus (FPV) vaccine. Therefore, exogenous CIAV contamination was suspected. We detected anti-CIAV antibodies in SPF chicks vaccinated with the FPV vaccine. CIAV contamination was confirmed in the FPV vaccine, and the CIAV strain was named JS2020-FPV. This study aims to rescue JS2020-FPV by reverse genetic assays and investigate its pathogenicity. Firstly, double-copies infectious clone of JS2020-FPV was constructed. For the pathogenicity study, infectious clone of JS2020-FPV was used to inoculate 1-day-old SPF chicks. The typical symptoms of anemia were observed in the JS2020-PFV group 14 days post inoculation. The hematocrit and body weight of chicks in the JS2020-PFV group were significantly lower than those in the mock group. Notably, the thymus development index and antibody levels of NDV were lower in chicks in the JS2020-PFV group than those in the mock group. Different degrees of apoptosis of MSB1 and DF-1 were observed after inoculated with the JS2020-FPV VP3 recombinant fusion protein expressed by E. coli system, indicating that VP3 induced apoptosis in the transformed cells. Overall, the pathogenicity of the CIAV detected in the contaminated vaccine was confirmed by inoculating SPF chicks with the double-copies infectious DNA clone in this study. Our findings indicate that the dangers of vaccine contamination cannot be ignored.

Quantitative reconstruction of regional paleotemperature is the key to understanding temperature change and its driving mechanisms. In this study, 133 phytolith samples were collected as proxy indicators from lacustrine sediments of the Zhunzhahanjilin (ZZH) profile in the hinterland of the Badain Jaran Desert, China. The phytolith samples were then analyzed to quantitatively reconstruct the Holocene paleotemperature at the millennial scale. Based on accelerator mass spectrometry (AMS), 14C dates and an ordered clustering method were used to divide the phytoliths into five assemblage zones with environmental significance. The quantitative reconstruction results indicated that the paleotemperature in the Badain Jaran Desert was relatively high during the early Holocene (11,040–8,200 cal a BP), and the average paleotemperature was approximately 9.5°C. This may have led to increased melt water near the surrounding area and recharged the lakes in the Badain Jaran Desert, resulting in the expansion of the lakes during the early Holocene. The average paleotemperature during the middle Holocene (8,200–3,100 cal a BP) was approximately 7.9°C. This period was warm and the environment was humid, with extensive precipitation from summer monsoons and low evaporation leading to higher water levels in the lakes. The paleotemperature decreased during the late Holocene (3,100 cal a BP to the present), and lakes retreated or dried up because of the decreased summer monsoon rains. The Holocene paleotemperature in the Badain Jaran Desert may have been related to July insolation in the Northern Hemisphere and had a range of impacts on the hydrological cycle in this arid region.

Abstract Atrial fibrillation (AF) is an increasingly prevalent arrhythmia with significant health and socioeconomic impact. The underlying mechanism of AF is still not well understood. In this study, we sought to identify hub genes involved in AF, and explored their functions and underlying mechanisms based on bioinformatics analysis. Five microarray datasets in GEO were used to identify the differentially expressed genes (DEGs) by Robust Rank Aggregation (RRA), and hub genes were screened out using protein–protein interaction (PPI) network. AF model was established using a mixture of acetylcholine and calcium chloride (Ach-CaCl2) by tail vein injection. We totally got 35 robust DEGs that mainly involve in extracellular matrix formation, leukocyte transendothelial migration, and chemokine signaling pathway. Among these DEGs, we identified three hub genes involved in AF, of which CXCL12/CXCR4 axis significantly upregulated in AF patients stands out as one of the most potent targets for AF prevention, and its effect on AF pathogenesis and underlying mechanisms were investigated in vivo subsequently with the specific CXCR4 antagonist AMD3100 (6 mg/kg). Our results demonstrated an elevated transcription and translation of CXCL12/CXCR4 axis in AF patients and mice, accompanied with the anabatic atrial inflammation and fibrosis, thereby providing the substrate for AF maintenance. Blocking its signaling via AMD3100 administration in AF model mice reduced AF inducibility and duration, partly ascribed to decreased atrial inflammation and structural remodeling. Mechanistically, these effects were achieved by reducing the recruitment of CD3+ T lymphocytes and F4/80+ macrophages, and suppressing the hyperactivation of ERK1/2 and AKT/mTOR signaling in atria of AF model mice. In conclusion, this study provides new evidence that antagonizing CXCR4 prevents the development of AF, and suggests that CXCL12/CXCR4 axis may be a potential therapeutic target for AF.

Abstract Background Endometriosis is a chronic hormonal inflammatory disease characterized by the presence of endometrial tissue outside the uterus. Endometriosis often causes infertility, which brings physical and mental pain to patients and their families. Methods We examined the functions of heat shock factor 1 (HSF1) in endometriosis development through cell count assay, cell-scratch assay and clone formation experiments. We used quantitative real-time PCR (qRT-PCR) and Western blot (WB) to detect HSF1 expression. Glucose and lactate levels were determined using a glucose (GO) assay kit and a lactate assay kit. Furthermore, we used a HSF1 inhibitor-KRIBB11 to establish a mouse model of endometriosis. Results Our data demonstrated that HSF1 promoted endometriosis development. Interestingly, HSF1 enhanced glycolysis via up-regulating PFKFB3 expression in endometriosis cells, which was a key glycolysis enzyme. Consistently, the HSF1 inhibitor KRIBB11 could abrogate endometriosis progression in vivo and in vitro. Conclusions Findings indicate that HSF1 plays an important role in endometriosis development, which might become a new target for the treatment of endometriosis. Electronic supplementary material Supplementary data are available.

Live attenuated vaccines have been extensively used to prevent infectious disease in poultry flocks. Freedom from exogenous virus is a high priority for any veterinary vaccines. Recently, attenuated Newcastle disease virus (NDV) vaccines were detected to be contaminated with chicken infectious anemia virus (CIAV) in a routine screening for exogenous viruses. To investigate the possible source of the contamination, we conducted virological tests on a specific-pathogen-free (SPF) layer breeder flock that provide the raw materials for vaccines in this manufacturer. Firstly, CIAV antibodies in serum and egg yolks samples of the SPF laying hens were detected by ELISA assays. The results showed that CIAV antibodies in serum and egg yolks were 62% positive and 57% positive, respectively. Then, DNA was extracted from the NDV vaccines and SPF chicken embryonated eggs, and detected by molecular virology assays. The results showed that three assays for pathogens in embryonated eggs had similar positive rates (35.8%). And the sequences of CIAV from SPF embryos and NDV vaccines consisted of 2,298 nucleotides (nt) with 100% homology. The new full-length genome of CIAV was designated SDSPF2020 (Genbank accession number: MW660821). Data showed SDSPF2020 had the sequence similarities of 95.8–99.6% with reference strains, and shared the highest homology with the Chinese strain HLJ15125. These results strongly suggested that exogenous CIAV contamination is most likely caused by wild virus infection in SPF flocks and vertical transmission to chicken embryos. Collectively, this study illustrated that vertical transmission of CIAV from a SPF layer breeder flock to embryos was a non-neglible way for exogenous virus contamination in vaccine production.

ObjectiveTo investigate voxel-based morphometry (VBM) by using magnetic resonance imaging (MRI) in meibomian gland dysfunction patients with severe obesity (PATs) and to explore the application of VBM in the early diagnosis, prevention of cognitive impairment and targeted treatment of this disease.MethodsSixteen PATs and 12 healthy controls (HCs) were enrolled and underwent MRI. Whole-head images were analyzed using VBM and data were compared between groups using an independent samples t-test. Receiver operating characteristic (ROC) curves were utilized to assess the diagnostic value of this approach. Mini-mental state examination (MMSE) scores were used to assess cognitive impairment and were analyzed using an independent samples t-test.ResultsCompared with HCs, the VBM values in PATs were reduced in the left cerebellum and right thalamus but increased in the right brainstem, right precuneus and right paracentral lobule. The results of ROC curve analysis indicated that VBM may be useful in meibomian gland disease diagnosis. Comparison of MMSE scores between groups showed mild cognitive impairment in PATs.ConclusionPATs showed altered VBM values in some brain areas. These findings may provide information about the pathophysiology of meibomian gland dysfunction and may help to explain the underlying mechanisms of clinical manifestations in PATs, such as cognitive impairment. Abnormal VBM values in these brain areas may serve as predictive factors for development of meibomian gland disease in severely obese people and as indicators for individualized treatment.

Abstract Immunotherapy strategies that use cell‐based delivery systems have sparked much interest in the treatment of malignancies, owing to their high biocompatibility, excellent tumor targeting capability, and unique biofunctionalities in the tumor growth process. A variety of design principles for cell‐based immunotherapy, including cell surface decoration, cell membrane coating, cell encapsulation, genetically engineered cell, and cell‐derived exosomes, give cancer immunotherapy great potential to improve therapeutic efficacy and reduce adverse effects. However, the treatment efficacy of cell‐based delivery methods for immunotherapy is still limited, and practical uses are hampered due to complex physiological and immunological obstacles, such as physical barriers to immune infiltration, immunosuppressive tumor microenvironment, upregulation of immunosuppressive pathways, and metabolic restriction. In this review, we present an overview of the design principles of cell‐based delivery systems in cancer immunotherapy to maximize the therapeutic impact, along with anatomical, metabolic, and immunological impediments in using cell‐based immunotherapy to treat cancer. Following that, a summary of novel delivery strategies that have been created to overcome these obstacles to cell‐based immunotherapeutic delivery systems is provided. Also, the obstacles and prospects of next‐step development of cell‐based delivery systems for cancer immunotherapy are concluded in the end.

PD-1/PD-L1 play key roles in tumor immune escape and the formation of the tumor microenvironment, and are closely related to the generation and development of tumors. Blocking the PD-1/PD-L1 pathway can reshape the tumor microenvironment or block the formation of the tumor microenvironment and enhance endogenous antitumor immune response. Clinical trials show that the treatment of non-small cell lung cancer (NSCLC) with PD-1/PD-L1 inhibitors has significant advantages. The review briefly describes these basic principles of the PD-1/PD-L1 pathway and action mechanism in the treatment of NSCLC. A summary of global PD-1/PD-L1 clinical trials and five PD-1/PD-L1 inhibitors approved by FDA, EMA and NMPA for advanced NSCLC were analyzed.

Chicken infectious anemia virus (CIAV) can be transmitted by contaminated live vaccines, and causes huge economic losses. This study evaluated the contamination status of CIAV in 24 batches of vaccines by recombinase-aided amplification assay (RAA), fluorescence quantitative PCR and dot blot assay, and then found a contaminated attenuated vaccine. The whole genome of the CIAV contaminant was then sequenced and named JS2020-PFV (Genbank accession number: MW234428, 2296bp). It showed 94.5 to 99.9% identities with reference strains and shared the closest evolution relationship with AB1K strain which was isolated from a chicken farm in Turkey. All of these suggested that the use of CIAV contaminated live vaccine may be one of the reason for its epidemic in poultry.