Search

Abstract Background Brassica napus L. (B. napus) is susceptible to waterlogging stress during different cultivation periods. Therefore, it is crucial to enhance the resistance to waterlogging stress to achieve a high and stable yield of B. napus. Results Here we observed significant differences in the responses of two B. napus varieties in root under waterlogging stress. The sensitive variety (23651) exhibited a more pronounced and rapid reduction in cell wall thickness and root integrity compared with the tolerant variety (Santana) under waterlogging stress. By module clustering analysis based on transcriptome data, we identified that cell wall polysaccharide metabolism responded to waterlogging stress in root. It was found that pectin content was significantly reduced in the sensitive variety compared with the tolerant variety. Furthermore, transcriptome analysis revealed that the expression of two homologous genes encoding polygalacturonase-inhibiting protein 2 (PGIP2), involved in polysaccharide metabolic pathways, was highly upregulated in root of the tolerant variety under waterlogging stress. BnaPGIP2s probably confer waterlogging resistance by inhibiting the activity of polygalacturonases (PGs), which in turn reduces the degradation of the pectin backbone polygalacturonic acid. Conclusions Our findings demonstrate that cell wall polysaccharides in root plays a vital role in response to the waterlogging stress and provide a theoretical foundation for breeding waterlogging resistance in B. napus varieties.

Abstract Background Phosphorus is a macronutrient necessary for plant growth and development and its availability and efficient use affect crop yields. Leaves are the largest tissue that uses phosphorus in plants, and membrane phospholipids are the main source of cellular phosphorus usage. Results Here we identify a key process for plant cellular phosphorus recycling mediated by membrane phospholipid hydrolysis during leaf senescence. Our results indicate that over 90% of lipid phosphorus, accounting for more than one-third of total cellular phosphorus, is recycled from senescent leaves before falling off the plants. Nonspecific phospholipase C4 (NPC4) and phospholipase Dζ2 (PLDζ2) are highly induced during leaf senescence, and knockouts of PLDζ2 and NPC4 decrease the loss of membrane phospholipids and delay leaf senescence. Conversely, overexpression of PLDζ2 and NPC4 accelerates the loss of phospholipids and leaf senescence, promoting phosphorus remobilization from senescent leaves to young tissues and plant growth. We also show that this phosphorus recycling process in senescent leaves mediated by membrane phospholipid hydrolysis is conserved in plants. Conclusions These results indicate that PLDζ2- and NPC4-mediated membrane phospholipid hydrolysis promotes phosphorus remobilization from senescent leaves to growing tissues and that the phospholipid hydrolysis-mediated phosphorus recycling improves phosphorus use efficiency in plants.

Abstract DNA base editors enable direct editing of adenine (A), cytosine (C), or guanine (G), but there is no base editor for direct thymine (T) editing currently. Here we develop two deaminase-free glycosylase-based base editors for direct T editing (gTBE) and C editing (gCBE) by fusing Cas9 nickase (nCas9) with engineered human uracil DNA glycosylase (UNG) variants. By several rounds of structure-informed rational mutagenesis on UNG in cultured human cells, we obtain gTBE and gCBE with high activity of T-to-S (i.e., T-to-C or T-to-G) and C-to-G conversions, respectively. Furthermore, we conduct parallel comparison of gTBE/gCBE with those recently developed using other protein engineering strategies, and find gTBE/gCBE show the outperformance. Thus, we provide several base editors, gTBEs and gCBEs, with corresponding engineered UNG variants, broadening the targeting scope of base editors.

BackgroundHemorrhagic fever with renal syndrome (HFRS) is a vital rodent-borne disease, and poses a serious public health threat in Hubei province. We aimed to explore the spatiotemporal distribution of HFRS in Hubei province during 2005-2022, and the effects of meteorological factors.MethodsData on HFRS cases at the county level in Hubei province during 2005-2022 were obtained from the Chinese Center for Disease Prevention and Control Information System. The monthly meteorological data at the city level was extracted from the China Meteorological Data Sharing Service System from 2016 to 2020. Descriptive analyses, joinpoint regression model, spatial correlation analyses, Geodetector model and autoregressive integrated moving average (ARIMA) model were conducted to investigate the epidemic characteristics, temporal trend, spatial distribution, influencing factors of HFRS and predict its trend.ResultsA total of 6,295 cases were reported in Hubei province during 2005-2022, with an average incidence of 6/1,000,000. Most cases were males (74.52%) and aged 40-69 years (71.87%). The monthly HFRS cases showed two seasonal peaks, which were summer (May to June) and winter (November to December). The HFRS incidence remained fluctuating at a low level during 2005-2015, followed an increasing trend during 2015-2018, and then decreased during 2018-2022. Hotspots were concentrated in the center of Hubei province in all 3 periods, including Qianjiang, Tianmen and some counties from Xiangyang, Jingmen and Jingzhou cities. The distribution of HFRS had a positive association with wind speed, while a "V"-shaped correlation with mean temperature, with an explanatory power of 3.21% and 1.03% respectively (both P ConclusionsHFRS cases showed seasonal fluctuation and spatial clustering in Hubei province. Central plain areas showed high risk of HFRS. Wind speed and mean temperature had significant effects on the transmission of HFRS in Hubei province. The results alert health authorities to conduct disease-climate surveillance and comprehensive prevention strategies, especially in high-risk counties.

The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has incurred devastating human and economic losses. Vaccination remains the most effective approach for controlling the COVID-19 pandemic. Nonetheless, the sustained evolution of SARS-CoV-2 variants has provoked concerns among the scientific community regarding the development of next-generation COVID-19 vaccines. Among these, given their safety, immunogenicity, and flexibility to display varied and native epitopes, virus-like particle (VLP)-based vaccines represent one of the most promising next-generation vaccines. In this review, we summarize the advantages and characteristics of VLP platforms, strategies for antigen display, and current clinical trial progress of SARS-CoV-2 vaccines based on VLP platforms. Importantly, the experience and lessons learned from the development of SARS-CoV-2 VLP vaccines provide insights into the development of strategies based on VLP vaccines to prevent future coronavirus pandemics and other epidemics.

Highlights An ultraconformable skin-like integrated wireless charging micro-supercapacitor (IWC-MSC) could be wireless charged to store electricity into high capacitive micro-supercapacitors (11.39 F cm−3), and fits well with human surface. Building blocks of IWC-MSC skin are all evaporated by liquid precursor, and each part of the device attached firmly benefitting from the liquid permeation, forming a compact and all-in-one configuration. The electrode thickness easily regulated varying from 11.7 to 112.5 μm by controlling the volume of electrode solution precursor.

Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the growing advances in technologies in isolation and identification of natural products, the potential of natural products in combating cancer multidrug resistance has received substantial attention. Importantly, natural products can impact multiple targets, which can be valuable in overcoming drug resistance from different perspectives. In the current review, we will describe the well-established mechanisms underlying multidrug resistance, and introduce natural products that could target these multidrug resistant mechanisms. Specifically, we will discuss natural compounds such as curcumin, resveratrol, baicalein, chrysin and more, and their potential roles in combating multidrug resistance. This review article aims to provide a systematic summary of recent advances of natural products in combating cancer drug resistance, and will provide rationales for novel drug discovery.

Reactive oxygen species (ROS) play a key role in a variety of biological processes, such as the perception of abiotic stress, the integration of different environmental signals, and the activation of stress response networks. Salt stress could induce an increased ROS accumulation in plants, disrupting intracellular redox homeostasis, leading to post-translational modifications (PTMs) of specific proteins, and eventually causing adaptive changes in metabolism. Here, we performed an iodoTMT-based proteomic approach to identify the sulfenylated proteins in B. napus root responsing to salt stress. Totally, 1 348 sulfenylated sites in 751 proteins were identified and these proteins were widely existed in different cell compartments and processes. Our study revealed that proteins with changed abundance and sulfenylation level in B. napus root under salt stress were mainly enriched in the biological processes of ion binding, glycolysis, ATP binding, and oxidative stress response. This study displays a landscape of sulfenylated proteins response to salt stress in B. napus root and provides some theoretical support for further understanding of the molecular mechanisms of redox regulation under salt stress in plants.

Abstract Background Brassica napus is an important oilseed crop providing high-quality vegetable oils for human consumption and non-food applications. However, the regulation between embryo and seed coat for the synthesis of oil and phenylpropanoid compounds remains largely unclear. Results Here, we analyzed the transcriptomes in developing seeds at 2-day intervals from 14 days after flowering (DAF) to 64 DAF. The 26 high-resolution time-course transcriptomes are clearly clustered into five distinct groups from stage I to stage V. A total of 2217 genes including 136 transcription factors, are specifically expressed in the seed and show high temporal specificity by being expressed only at certain stages of seed development. Furthermore, we analyzed the co-expression networks during seed development, which mainly included master regulatory transcription factors, lipid, and phenylpropane metabolism genes. The results show that the phenylpropane pathway is prominent during seed development, and the key enzymes in the phenylpropane metabolic pathway, including TT5, BAN, and the transporter TT19, were directly or indirectly related to many key enzymes and transcription factors involved in oil accumulation. We identified candidate genes that may regulate seed oil content based on the co-expression network analysis combined with correlation analysis of the gene expression with seed oil content and seed coat content. Conclusions Overall, these results reveal the transcriptional regulation between lipid and phenylpropane accumulation during B. napus seed development. The established co-expression networks and predicted key factors provide important resources for future studies to reveal the genetic control of oil accumulation in B. napus seeds.

Benefiting from the robust feature representation capability of convolutional neural networks (CNNs), the object detection technology of intelligent high-altitude UAV remote sensing has been developed rapidly. In this field, the adversarial examples (AEs) pose serious security risks and vulnerabilities to deep learning-based systems. Due to the limitation of object size, image degradation, and scene brightness, adding adversarial disturbances to small and dense objects is extremely challenging. To study the threat of AE for UAV object detection, a dynamic bi-level integrated attack (DBI-Attack) is proposed for intensive multi-scale UAV object detection. Firstly, we use the dynamic iterative attack (DIA) method to generate perturbation on the classification level by improving the momentum iterative fast gradient sign method (MIM). Secondly, the bi-level adversarial attack method (BAAM) is constructed to add global perturbation on the decision level for completing the white-box attack. Finally, the integrated black-box attack method (IBAM) is combined to realize the black-box mislabeling and fabrication attacks. We experiment on the real drone traffic vehicle detection datasets to better evaluate the attack effectiveness. The experimental results show that the proposed method can achieve mislabeling and fabrication attacks on the UAV object detectors in black-box conditions. Furthermore, the adversarial training is applied to improve the model robustness. This work aims to call more attention to the adversarial and defensive aspects of UAV target detection models.

Paprika oleoresin (PO) is extensively utilized as a natural pigment in the food industry. However, its application in aqueous phase foods is hindered by due to its lipophilicity and sensitivity to oxygen, heat, and light. This study developed an aqueous PO solution using low-density lipoprotein (LDL) as a carrier, which was remodeled through high pressure homogenization treatment (0–100 MPa). Comprehensive analyses were conducted to characterize the micro-morphology, particle size, potential, and encapsulation efficiency (EE) of the solution, alongside evaluations of its storage, thermal, and ultraviolet (UV) irradiation stability, in addition to physicochemical and structural characterization of the remodeled LDL. The results showed that after high pressure homogenization (100 MPa, 10 cycles) treatment, the delamination of LDL-PO solution was significantly reduced, the average particle size decreased by 37.2%, the EE increased by 9.2%, and the storage, thermal, and UV irradiation stability increased from 30.83%, 64.42%, and 77.56% to 62.90%, 76.97%, and 92.98%, respectively. In addition, sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorescence spectroscopy analyses revealed that high pressure homogenization treatment enhanced the interaction and binding between LDL and PO, thus significantly improved the solubility and stability of PO in water. In this study, an aqueous solution of PO with higher stability and embedding rate was obtained by the greener and safer high pressure homogenization technique, offering new avenues for PO application in the food industry and innovative uses of LDL as a carrier for bioactive substances.

Objective: Allergic rhinitis (AR) is a disease associated with impaired quality of life and heredity. This study aimed to investigate the association of allergic rhinitis in preschool children with exposure to indoor environment-related factors early in life. Methods: In August 2019, the authors implemented a study among 2020 preschool children in Urumqi City using a case-control design. The study included parental reports for the occurrence of AR in children, parental history of respiratory disease, and indoor environmental correlates of maternal exposure from 1 year prior to pregnancy until the child's age of 0-1 year. Results: Mode of birth (cesarean section) (OR = 1.31, 95% CI = 1.02∼1.67), father with AR (OR = 2.67, 95% CI = 2.08∼3.44), mother with AR (OR = 3.70, 95% CI = 2.88∼4.74), mother with asthma (OR = 3.11, 95% CI = 1.18∼8.20), and mother with newly purchased furniture in the parents' residence during pregnancy (OR = 1.49, 95% CI = 1.03∼2.14) were risk factors for AR in children. Conclusions: The focus of allergic rhinitis should be on children with a family history of AR and asthma and cesarean delivery. Primary prevention efforts for AR in preschool children are avoiding exposure of children to indoor environmental hazardous factors early in life.

Abstract The enolimine-ketoenamine tautomerism has been utilised to construct 2D covalent organic frameworks (COFs) with a higher level of chemical robustness and superior photoelectronic activity. However, it remains challenging to fully control the tautomeric states and correlate their tautomeric structure-photoelectronic properties due to the mobile equilibrium of proton transfer between two other atoms. We show that symmetry-asymmetry tautomerisation from diiminol to iminol/cis-ketoenamine can be stabilised and switched in a crystalline, porous, and dynamic 3D COF (dynaCOF-301) through concerted structural transformation and host-guest interactions upon removal and adaptive inclusion of various guest molecules. Specifically, the tautomeric dynaCOF-301 is constructed by linking the hydroquinone with a tetrahedral building block through imine linkages to form 7-fold interwoven diamondoid networks with 1D channels. Reversible framework deformation and ordering-disordering transition are determined from solvated to activated and hydrated phases, accompanied by solvatochromic and hydrochromic effects useful for rapid, steady, and visual naked-eye chemosensing.

Abstract Background Seed oil content is an important agronomic trait of Brassica napus (B. napus), and metabolites are considered as the bridge between genotype and phenotype for physical traits. Results Using a widely targeted metabolomics analysis in a natural population of 388 B. napus inbred lines, we quantify 2172 metabolites in mature seeds by liquid chromatography mass spectrometry, in which 131 marker metabolites are identified to be correlated with seed oil content. These metabolites are then selected for further metabolite genome-wide association study and metabolite transcriptome-wide association study. Combined with weighted correlation network analysis, we construct a triple relationship network, which includes 21,000 edges and 4384 nodes among metabolites, metabolite quantitative trait loci, genes, and co-expression modules. We validate the function of BnaA03.TT4, BnaC02.TT4, and BnaC05.UK, three candidate genes predicted by multi-omics analysis, which show significant impacts on seed oil content through regulating flavonoid metabolism in B. napus. Conclusions This study demonstrates the advantage of utilizing marker metabolites integrated with multi-omics analysis to dissect the genetic basis of agronomic traits in crops.

Reactive oxygen burst in articular chondrocytes is a major contributor to osteoarthritis progression. Although selenium is indispensable role in the antioxidant process, the narrow therapeutic window, delicate toxicity margins, and lack of an efficient delivery system have hindered its translation to clinical applications. Herein, transcriptomic and biochemical analyses revealed that osteoarthritis was associated with selenium metabolic abnormality. A novel injectable hydrogel to deliver selenium nanoparticles (SeNPs) was proposed to intervene selenoprotein expression for osteoarthritis treatment. The hydrogels based on oxidized hyaluronic acid (OHA) cross-linked with hyaluronic acid-adipic acid dihydrazide (HA-ADH) was formulated to load SeNPs through a Schiff base reaction. The hydrogels were further incorporated with SeNPs, which exhibited minimal toxicity, mechanical properties, self-healing capability, and sustained drug release. Encapsulated with SeNPs, the hydrogels facilitated cartilage repair through synergetic effects of scavenging reactive oxygen species (ROS) and depressing apoptosis. Mechanistically, the hydrogel restored redox homeostasis by targeting glutathione peroxidase-1 (GPX1). Therapeutic outcomes of the SeNPs-laden hydrogel were demonstrated in an osteoarthritis rat model created by destabilization of the medial meniscus, including cartilage protection, subchondral bone sclerosis improvement, inflammation attenuation, and pain relief were demonstrated. These results highlight therapeutic potential of OHA/HA-ADH@SeNPs hydrogels, providing fundamental insights into remedying selenium imbalance for osteoarthritis biomaterial development.

Mutations within viral epitopes can result in escape from T cells, but the contribution of mutations in flanking regions of epitopes in SARS-CoV-2 has not been investigated. Focusing on two SARS-CoV-2 nucleoprotein CD8+ epitopes, we investigated the contribution of these flanking mutations to proteasomal processing and T cell activation. We found decreased NP9-17-B*27:05 CD8+ T cell responses to the NP-Q7K mutation, likely due to a lack of efficient epitope production by the proteasome, suggesting immune escape caused by this mutation. In contrast, NP-P6L and NP-D103 N/Y mutations flanking the NP9-17-B*27:05 and NP105-113-B*07:02 epitopes, respectively, increased CD8+ T cell responses associated with enhanced epitope production by the proteasome. Our results provide evidence that SARS-CoV-2 mutations outside the epitope could have a significant impact on proteasomal processing, either contributing to T cell escape or enhancement that may be exploited for future vaccine design.

The Corona Virus Disease 2019 (COVID-19) epidemic has deferred global progress in energy efficiency to a decade-long low, posing a threat to the achievement of international climate goals, and also profoundly affected the development of economics. To gain insight into the research frontiers and hotspots in energy efficiency and COVID-19, a systematic literature review and bibliometric analysis on economic effects are performed with the help of the bibliometric tools VOSviewer and Bibliometrix. This paper selects all the publications retrieved based on the subject terms in the Web of Science core collection. Firstly, this article performs a performance analysis of related publications to present the development and distribution of energy efficiency and COVID-19 from research areas, relevant sources, and influential articles. Afterward, a visual analysis of the literature called science mapping analysis is implemented to display the structural and dynamic organization of knowledge in energy efficiency and COVID-19 research. In the end, detailed discussions of two research hotspots and some theoretical and practical implications are concluded in the systematic literature review and bibliometric analysis findings, which may contribute to further development for researchers in the field of energy efficiency and eventually propel the progress of society and economy in an all-round way. First published online 06 October 2023

IntroductionThis study aimed to investigate pathological changes in the “Glutamate (Glu)-γ-aminobutyric acid (GABA)” loop and apply widely targeted metabolomic analysis technology to comprehensively explore metabolite abnormalities/ in the thalamus of rats with tic disorders (TD).MethodsWistar rats were randomized into control, TD, and tiapride (Tia) groups. Iminodipropionitrile (IDPN) was used to induce TD in rats. The Tia group was administered tiapride. Neurotransmitter levels in the thalamus of rats in the three groups were measured using UPLC-3Q MS. And, the protein expression levels of Glu decarboxylase (GAD65/67) and GABA transporter protein (GAD-T) were measured using western blotting. The mRNA expression levels of these genes were evaluated using real-time polymerase chain reaction. Lastly, other metabolites in the thalamus were detected by widely targeted metabolomic analysis between TD and Control group rats.ResultsThe Glu level, Glu/GABA ratio, and Asp level in the TD group were significantly higher (all p

Shanghai University School of Medicine was a newly established medical college in 2018. It is founded on the national health development policies, international medical development trends and the close relationship between the advantages of new medical courses and medical artificial intelligence, it is dedicated to using intelligent medicine as the breakthrough point, training graduate students in two interdisciplinary medical engineering subjects as the priority, and implementing the integrated medical curriculum teaching reform. In this paper, we introduce the background of the integrated medical curriculum system at the Shanghai University School of Medicine, the horizontal and vertical integration of medical courses in interdisciplinary medical engineering subjects, the cross-integration of traditional integrated medical courses with other disciplines and specialties, and the transformation mode of medical science and technology innovation led by artificial intelligence under the support of three-dimensional curriculum integration, putting forward the prospect of the curriculum integration system and providing experiences and references for other medical schools. KEY MESSAGESThis paper introduces the necessity and feasibility of implementing integrated medical course teaching in a newly established medical college.This paper introduces the strategies and concrete measures we took to implement integrated medical course teaching.The analysis of examination papers and other evaluations revealed that the integrated medical teaching for graduate students with non-medical professional backgrounds is feasible.

The complete mitogenome sequence of the flea, Hystrichopsylla weida qinlingensis (Siphonaptera: Hystrichopsylla) was sequenced. The 17,173 bp long genome has the standard metazoan complement of 37 genes. These genes contain 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and one control region. The nucleotide composition of the H. weida qinlingensis mitogenome was A: 39.10%, T: 41.49%, G:7.56%, and C: 11.85%. The A + T content is 80.59%, showing strong AT bias. Phylogenetic analysis indicates that Hystrichopsylla has a close affinity with a branch of Dorcadia.

Abstract Background Regulation of gene expression plays an essential role in controlling the phenotypes of plants. Brassica napus (B. napus) is an important source for the vegetable oil in the world, and the seed oil content is an important trait of B. napus. Results We perform a comprehensive analysis of the transcriptional variability in the seeds of B. napus at two developmental stages, 20 and 40 days after flowering (DAF). We detect 53,759 and 53,550 independent expression quantitative trait loci (eQTLs) for 79,605 and 76,713 expressed genes at 20 and 40 DAF, respectively. Among them, the local eQTLs are mapped to the adjacent genes more frequently. The adjacent gene pairs are regulated by local eQTLs with the same open chromatin state and show a stronger mode of expression piggybacking. Inter-subgenomic analysis indicates that there is a feedback regulation for the homoeologous gene pairs to maintain partial expression dosage. We also identify 141 eQTL hotspots and find that hotspot87-88 co-localizes with a QTL for the seed oil content. To further resolve the regulatory network of this eQTL hotspot, we construct the XGBoost model using 856 RNA-seq datasets and the Basenji model using 59 ATAC-seq datasets. Using these two models, we predict the mechanisms affecting the seed oil content regulated by hotspot87-88 and experimentally validate that the transcription factors, NAC13 and SCL31, positively regulate the seed oil content. Conclusions We comprehensively characterize the gene regulatory features in the seeds of B. napus and reveal the gene networks regulating the seed oil content of B. napus.

Abstract Objective We aimed to investigate the relationship between the expression of killer cell lectin like receptor G1 (KLRG1) in peripheral blood lymphocytes, and the clinical characteristics and prognosis in patients with locally advanced nasopharyngeal carcinoma (NPC), and to dynamically evaluate the changes of KLRG1 expression after treatment. Methods A total of 82 patients with locally advanced NPC and 44 healthy individuals were recruited in this study. The expression of KLRG1 on T, natural killer, and natural killer T cells in peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. Its relationship with clinical characteristics and prognosis of patients, as well as changes in KLRG1 expression in PBMCs after treatment, were investigated. Results The expression of KLRG1 in CD8+ T cells in PBMCs of NPC patients was 46.50 (29.10, 69.80)%, significantly higher than 32.50 (17.38, 61.00) % in healthy controls (Z = −2.290, p = 0.022). The expression of KLRG1 in CD3+ CD56+ natural killer T cells in PBMCs of patients was 29.50 (6.21, 78.00) %, significantly higher than 1.47 (0.62, 8.88)% in healthy controls (Z = −5.371, p

The use of immune checkpoint inhibitors in malignant tumors improves patient outcomes. Because single-agent immune checkpoint blockade has a low objective response rate, it is meaningful to explore combined blockade of immune checkpoint receptors. We aimed to investigate the co-expression of TIM-3 with TIGIT or 2B4 on peripheral blood CD8+ T cells from patients with locally advanced nasopharyngeal carcinoma. The correlation between co-expression level and clinical characteristics and prognosis was studied to provide a basis for immunotherapy for nasopharyngeal carcinoma. Flow cytometry was used to detect TIM-3/TIGIT and TIM-3/2B4 co-expression on CD8+ T cells. The differences in co-expression between patients and healthy controls were analyzed. The correlation between co-expression of TIM-3/TIGIT or TIM-3/2B4 and the patient clinical characteristics and prognosis was examined. Also, the correlation between the TIM-3/TIGIT or 2B4 co-expression and other common inhibitory receptors was analyzed. We further validated our results using mRNA data from the Gene Expression Omnibus (GEO) database. TIM-3/TIGIT and TIM-3/2B4 co-expression was upregulated on peripheral blood CD8+ T cells from patients with nasopharyngeal carcinoma. They were both correlated with poor prognosis. There was a correlation between TIM-3/TIGIT co-expression and patient age and pathological stage, whereas TIM-3/2B4 co-expression correlated with age and sex. CD8+ T cells with elevated mRNA levels of TIM3/TIGIT and TIM3/2B4 also showed increased expression of multiple inhibitory receptors, indicating T cell exhaustion in locally advanced nasopharyngeal carcinoma. TIM-3/TIGIT or TIM-3/2B4 can be used as potential targets for combination immunotherapy in locally advanced nasopharyngeal carcinoma.

Summary: T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis of this rapid response following SARS-COV-2 infection. We applied T cell receptor (TCR) sequencing to define the trajectories of individual T cell clones immediately. In SARS-COV-2 PCR+ individuals, a wave of TCRs strongly but transiently expand, frequently peaking the same week as the first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated as SARS-COV-2 specific. Epitopes recognized by the expanding TCRs were highly conserved between SARS-COV-2 strains but not with circulating human coronaviruses. Many expanding CDR3s were present at high frequency in pre-pandemic repertoires. Early response TCRs specific for lymphocytic choriomeningitis virus epitopes were also found at high frequency in the preinfection naive repertoire. High-frequency naive precursors may allow the T cell response to respond rapidly during the crucial early phases of acute viral infection.

Summary: Most existing studies characterizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses are peptide based. This does not allow evaluation of whether tested peptides are processed and presented canonically. In this study, we use recombinant vaccinia virus (rVACV)-mediated expression of SARS-CoV-2 spike protein and SARS-CoV-2 infection of angiotensin-converting enzyme (ACE)-2-transduced B cell lines to evaluate overall T cell responses in a small cohort of recovered COVID-19 patients and uninfected donors vaccinated with ChAdOx1 nCoV-19. We show that rVACV expression of SARS-CoV-2 antigen can be used as an alternative to SARS-CoV-2 infection to evaluate T cell responses to naturally processed spike antigens. In addition, the rVACV system can be used to evaluate the cross-reactivity of memory T cells to variants of concern (VOCs) and to identify epitope escape mutants. Finally, our data show that both natural infection and vaccination could induce multi-functional T cell responses with overall T cell responses remaining despite the identification of escape mutations.

Abstract Background Brassica napus is an important vegetable oil source worldwide. Seed coat content is a complex quantitative trait that negatively correlates with the seed oil content in B. napus. Results Here we provide insights into the genetic basis of natural variation of seed coat content by transcriptome-wide association studies (TWAS) and genome-wide association studies (GWAS) using 382 B. napus accessions. By population transcriptomic analysis, we identify more than 700 genes and four gene modules that are significantly associated with seed coat content. We also characterize three reliable quantitative trait loci (QTLs) controlling seed coat content by GWAS. Combining TWAS and correlation networks of seed coat content-related gene modules, we find that BnaC07.CCR-LIKE (CCRL) and BnaTT8s play key roles in the determination of the trait by modulating lignin biosynthesis. By expression GWAS analysis, we identify a regulatory hotspot on chromosome A09, which is involved in controlling seed coat content through BnaC07.CCRL and BnaTT8s. We then predict the downstream genes regulated by BnaTT8s using multi-omics datasets. We further experimentally validate that BnaCCRL and BnaTT8 positively regulate seed coat content and lignin content. BnaCCRL represents a novel identified gene involved in seed coat development. Furthermore, we also predict the key genes regulating carbon allocation between phenylpropane compounds and oil during seed development in B. napus. Conclusions This study helps us to better understand the complex machinery of seed coat development and provides a genetic resource for genetic improvement of seed coat content in B. napus breeding.

Stress field analysis is an essential part of umbilical component layout design. The stress field analysis of an umbilical, via numerical simulation, has commonly been applied in practical engineering. The high economic and time cost associated with numerical simulation and analysis of the stress field in an umbilical has been replaced by data-driven, deep-learning-based, real-time computational methods. In this study, a novel Pyramidal Efficient U-Net (PyEf-U-Net) network is proposed to predict the stress field distribution of the umbilical. The input dataset is obtained via the Differential Evolution-Generalized Lagrange Multiplier (DE-GLM) method, which is entered into the network for training, with a detailed discussion of the effects of hyperparameters such as optimizer, learning rate, and loss function on the performance of the network. The experimental research demonstrates that the proposed PyEf-U-Net can accurately predict the stress field of the umbilical in real time with a prediction accuracy of 94.2%, which is superior to other deep learning networks. The proposed method can provide an effective way for rapid mechanical analysis and design of the umbilical in practical engineering, while the method can be extended to the mechanical analysis and design of other similar marine engineering equipment structures.

Abstract Background T cell epitopes are polypeptide fragments presented to T cell receptors by MHC molecules encoded by human leukocyte antigen (HLA) genes after antigen-presenting cell processing, which is the basis for the study of antigen immune mechanism and multi-epitope vaccine. This study investigated T cell response to HPV16 E6 and E7 in patients with cervical squamous cell carcinoma (CSCC). Also, the HLA-A allele distribution was compared among patients and evaluated as a factor to predict prognosis in these patients. Materials and methods This study recruited a total of 76 patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIB–IIIB CSCC. Mononuclear cells were isolated from the peripheral blood before any treatment and then enzyme-linked immunosorbent spot (ELISpot) assay was employed to measure the E6 and E7-specific T cell response. HLA‐A alleles were typed using Sanger sequencing‐based typing techniques with DNA extracted from the peripheral blood. The correlation between the T cell responses, HLA‐A allele distribution and patient prognosis were analysed using the Kaplan–Meier method, univariate and multivariate Cox proportional hazard models. Results The frequency of HPV E6-specific T cell responses in patients with pelvic lymph node metastasis was lower than that in patients without metastasis (P = 0.022). The 5-year overall survival (OS) rates of patients were 87.5% for those responding to multiple overlapping peptides, 72.7% for those responding to 1–2 overlapping peptides and 47.7% for non-responders (P = 0.032). Cox regression analysis indicated that the presence of HLA*A02:07 was independently associated with worse OS (hazard ratio [HR] 3.042; 95% confidence interval [CI] 1.348–6.862; P = 0.007), while concurrent chemoradiation therapy (CCRT) was independently associated with better OS (HR 0.475; 95% CI 0.232–0.975; P = 0.042). Conclusion The results of our study demonstrated that the level of HPV16 E6-specific T cell response and HLA*A02:07 were correlated with prognosis in patients with advanced CSCC.

Abstract Epiretinal membrane (ERM) is a common ophthalmological disorder of high prevalence. Its symptoms include metamorphopsia, blurred vision, and decreased visual acuity. Early diagnosis and timely treatment of ERM is crucial to preventing vision loss. Although optical coherence tomography (OCT) is regarded as a de facto standard for ERM diagnosis due to its intuitiveness and high sensitivity, ophthalmoscopic examination or fundus photographs still have the advantages of price and accessibility. Artificial intelligence (AI) has been widely applied in the health care industry for its robust and significant performance in detecting various diseases. In this study, we validated the use of a previously trained deep neural network based-AI model in ERM detection based on color fundus photographs. An independent test set of fundus photographs was labeled by a group of ophthalmologists according to their corresponding OCT images as the gold standard. Then the test set was interpreted by other ophthalmologists and AI model without knowing their OCT results. Compared with manual diagnosis based on fundus photographs alone, the AI model had comparable accuracy (AI model 77.08% vs. integrated manual diagnosis 75.69%, χ2 = 0.038, P = 0.845, McNemar’s test), higher sensitivity (75.90% vs. 63.86%, χ2 = 4.500, P = 0.034, McNemar’s test), under the cost of lower but reasonable specificity (78.69% vs. 91.80%, χ2 = 6.125, P = 0.013, McNemar’s test). Thus our AI model can serve as a possible alternative for manual diagnosis in ERM screening.

Flowering time is strongly related to the environment, while the genotype-by-environment interaction study for flowering time is lacking in Brassica napus. Here, a total of 11,700,689 single nucleotide polymorphisms in 490 B. napus accessions were used to associate with the flowering time and related climatic index in eight environments using a compressed variance-component mixed model, 3VmrMLM. As a result, 19 stable main-effect quantitative trait nucleotides (QTNs) and 32 QTN-by-environment interactions (QEIs) for flowering time were detected. Four windows of daily average temperature and precipitation were found to be climatic factors highly correlated with flowering time. Ten main-effect QTNs were found to be associated with these flowering-time-related climatic indexes. Using differentially expressed gene (DEG) analysis in semi-winter and spring oilseed rapes, 5,850 and 5,511 DEGs were found to be significantly expressed before and after vernalization. Twelve and 14 DEGs, including 7 and 9 known homologs in Arabidopsis, were found to be candidate genes for stable QTNs and QEIs for flowering time, respectively. Five DEGs were found to be candidate genes for main-effect QTNs for flowering-time-related climatic index. These candidate genes, such as BnaFLCs, BnaFTs, BnaA02.VIN3, and BnaC09.PRR7, were further validated by the haplotype, selective sweep, and co-expression networks analysis. The candidate genes identified in this study will be helpful to breed B. napus varieties adapted to particular environments with optimized flowering time.

Redox regulation plays a wide role in plant growth, development, and adaptation to stresses. Sulfenylation is one of the reversible oxidative post-transcriptional modifications. Here we performed an iodoTMT-based proteomic analysis to identify the redox sensitive proteins in vivo under freezing stress after cold acclimation in Brassica napus. Totally, we obtained 1,372 sulfenylated sites in 714 proteins. The overall sulfenylation level displayed an increased trend under freezing stress after cold acclimation. We identified 171 differentially sulfenylated proteins (DSPs) under freezing stress, which were predicted to be mainly localized in chloroplast and cytoplasm. The up-regulated DSPs were mainly enriched in photosynthesis and glycolytic processes and function of catalytic activity. Enzymes involved in various pathways such as glycolysis and Calvin-Benson-Bassham (CBB) cycle were generally sulfenylated and the metabolite levels in these pathways was significantly reduced under freezing stress after cold acclimation. Furthermore, enzyme activity assay confirmed that the activity of cytosolic pyruvate kinase and malate dehydrogenase 2 was significantly reduced under H2O2 treatment. Our study provides a landscape of redox sensitive proteins in B. napus in response to freezing stress after cold acclimation, which proposes a basis for understanding the redox regulation in plant metabolic response to freezing stress after cold acclimation.

Abstract Background To evaluate the prevalence of myopia in school students in Urumqi, China, and explore the influence of the interaction between parental myopia and poor reading and writing habits on myopia to identify the at-risk population and provide evidence to help school students avoid developing myopia. Methods A cross-sectional survey was conducted with 6,883 school students aged 7–20 years in Urumqi in December 2019. The Standard Eye Chart and mydriatic optometry were used to determine whether students had myopia. Falconer’s method was used to calculate the heritability of parental myopia. Multivariate unconditional logistic regression models were used to analyze the risk factors for myopia and the additive and multiplicative interaction of parental myopia and poor reading and writing habits. Results After standardizing the age of the 6,883 students, the overall prevalence rate of myopia was 47.50 %. The heritability of parental myopia was 66.57 % for boys, 67.82 % for girls, 65.02 % for the Han group, and 52.71 % for other ethnicities. There were additive interactions between parental myopia and poor reading and writing habits; among them, parental myopia and poor eye habits when reading and writing (the distance between the eyes and book is less than 30 cm when reading and writing, fingers block the sight of one eye while holding the pen, and leaning one’s body when reading and writing; habit 1) increased the risk of myopia by 10.99 times (odds ratio [OR] = 10.99, 95 % confidence interval [CI] = 8.33–14.68), parental myopia and poor reading posture (reading while lying down, walking, or in the car; habit 2) increased the risk of myopia by 5.92 times (OR = 5.92, 95 % CI = 4.84–7.27). There was no multiplicative interaction between parental myopia and habit 1 or habit 2 (OR = 0.69, 95 % CI = 0.44–1.08; OR = 0.89, 95 % CI = 0.66–1.21, respectively). Conclusion The prevalence of myopia among students in Urumqi, Xinjiang is relatively high. The risk of developing myopia is affected by parental myopia and poor reading and writing habits. In addition, parental myopia amplifies the harm caused by poor reading and writing habits, thereby increasing the risk of myopia. Students with parents who have myopia should be targeted during myopia prevention efforts.

BackgroundThyroid-associated ophthalmopathy (TAO) is one of the most common orbital diseases that seriously threatens visual function and significantly affects patients’ appearances, rendering them unable to work. This study established an intelligent diagnostic system for TAO based on facial images.MethodsPatient images and data were obtained from medical records of patients with TAO who visited Shanghai Changzheng Hospital from 2013 to 2018. Eyelid retraction, ocular dyskinesia, conjunctival congestion, and other signs were noted on the images. Patients were classified according to the types, stages, and grades of TAO based on the diagnostic criteria. The diagnostic system consisted of multiple task-specific models.ResultsThe intelligent diagnostic system accurately diagnosed TAO in three stages. The built-in models pre-processed the facial images and diagnosed multiple TAO signs, with average areas under the receiver operating characteristic curves exceeding 0.85 (F1 score >0.80).ConclusionThe intelligent diagnostic system introduced in this study accurately identified several common signs of TAO.

Most plants are sensitive to salt-alkali stress, and the degree of tolerance to salt-alkali stress varies from different species and varieties. In order to explore the salt-alkali stress adaptability of Brassica napus, we collected the phenotypic data of 505 B. napus accessions at seedling and mature stages under control, low and high salt-alkali soil stress conditions in Inner Mongolia of China. Six resistant and 5 sensitive materials, respectively, have been identified both in Inner Mongolia and Xinjiang Uygur Autonomous Region of China. Genome-wide association studies (GWAS) for 15 absolute values and 10 tolerance coefficients (TCs) of growth and agronomic traits were applied to investigate the genetic basis of salt-alkali tolerance of B. napus. We finally mapped 9 significant QTLs related to salt-alkali stress response and predicted 20 candidate genes related to salt-alkali stress tolerance. Some important candidate genes, including BnABA4, BnBBX14, BnVTI12, BnPYL8, and BnCRR1, were identified by combining sequence variation annotation and expression differences. The identified valuable loci and germplasms could be useful for breeding salt-alkali-tolerant B.napus varieties. This study laid a foundation for understanding molecular mechanism of salt-alkali stress adaptation and provides rich genetic resources for the large-scale production of B. napus on salt-alkali land in the future.

Summary: Background: Pleural infection is a common and severe disease with high morbidity and mortality worldwide. The knowledge of pleural infection bacteriology remains incomplete, as pathogen detection methods based on culture have insufficient sensitivity and are biased to selected microbes. We designed a study with the aim to discover and investigate the total microbiome of pleural infection and assess the correlation between bacterial patterns and 1-year survival of patients. Methods: We assessed 243 pleural fluid samples from the PILOT study, a prospective observational study on pleural infection, with 16S rRNA next generation sequencing. 20 pleural fluid samples from patients with pleural effusion due to a non-infectious cause and ten PCR-grade water samples were used as controls. Downstream analysis was done with the DADA2 pipeline. We applied multivariate Cox regression analyses to investigate the association between bacterial patterns and 1-year survival of patients with pleural infection. Findings: Pleural infection was predominately polymicrobial (192 [79%] of 243 samples), with diverse bacterial frequencies observed in monomicrobial and polymicrobial disease and in both community-acquired and hospital-acquired infection. Mixed anaerobes and other Gram-negative bacteria predominated in community-acquired polymicrobial infection whereas Streptococcus pneumoniae prevailed in monomicrobial cases. The presence of anaerobes (hazard ratio 0·46, 95% CI 0·24–0·86, p=0·015) or bacteria of the Streptococcus anginosus group (0·43, 0·19–0·97, p=0·043) was associated with better patient survival, whereas the presence (5·80, 2·37–14·21, p

Most crops are sensitive to salt stress, but their degree of susceptibility varies among species and cultivars. In order to understand the salt stress adaptability of Brassica napus to salt stress, we collected the phenotypic data of 505 B. napus accessions at the germination stage under 150 or 215 mM sodium chloride (NaCl) and at the seedling stage under 215 mM NaCl. Genome-wide association studies (GWAS) of 16 salt tolerance coefficients (STCs) were applied to investigate the genetic basis of salt stress tolerance of B. napus. In this study, we mapped 31 salts stress-related QTLs and identified 177 and 228 candidate genes related to salt stress tolerance were detected at germination and seedling stages, respectively. Overexpression of two candidate genes, BnCKX5 and BnERF3 overexpression, were found to increase the sensitivity to salt and mannitol stresses at the germination stage. This study demonstrated that it is a feasible method to dissect the genetic basis of salt stress tolerance at germination and seedling stages in B. napus by GWAS, which provides valuable loci for improving the salt stress tolerance of B. napus. Moreover, these candidate genes are rich genetic resources for the following exploration of molecular mechanisms in adaptation to salt stress in B. napus.

A recent study has shown that demineralized cortical bone (DCB) did not improve the healing of tendon-bone interface. Considering that there is a gradient of mineral content in the tendon-bone interface, we designed a segmentally demineralized cortical bone (sDCB) scaffold with two different regions: undemineralized cortical bone section within the scaffold (sDCB-B) and complete demineralized cortical bone section within the scaffold (sDCB-D), to mimic the natural structure of the tendon-bone interface. Furthermore, the extracellular matrix (ECM) from tendon-derived stem cells (TDSCs) was used to modify the sDCB-D region of sDCB to construct a novel scaffold (sDCB-ECM) for enhancing the bioactivity of the sDCB-D. The surface topography, elemental distribution, histological structure, and surface elastic modulus of the scaffold were observed using scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, histological staining and atomic force microscopy. Cell proliferation of bone marrow mesenchymal stem cells (BMSCs) and TDSCs cultured on scaffolds was evaluated using the Cell Counting kit-8, and cell viability was assessed by Live/Dead cell staining. Cell morphology was detected by fluorescent staining. The ability of the scaffolds to recruit stem cells was tested using transwell migration assay. The expression levels of bone-, cartilage- and tendon-related genes and proteins in stem cells were assessed by the polymerase chain reaction and western blotting. Our results demonstrated that there was a gradient of Ca and P elements in sDCB, and TDSC-derived ECM existed on the surface of the sDCB-D region of sDCB. The sDCB-ECM could promote stem cell proliferation and migration. Moreover, the sDCB-B region of sDCB-ECM could stimulate osteogenic and chondrogenic differentiation of BMSCs, and the sDCB-D-ECM region of sDCB-ECM could stimulate chondrogenic and tenogenic differentiation of TDSCs when compared to DCB. Our study indicated that sDCB-ECM might be a potential bioscaffold to enhance the tendon-bone interface regeneration.

Cardamine lyrata Bunge 1833 grows near paddy fields, streams and shallow water. Its young stems and leaves can be eaten. It can also be used as medicine and has the effect of clearing away heat and dampness. The complete chloroplast genome sequence of the C. lyrata was determined and assembled. The complete genome is 155,170 bp in length, including a large single-copy region (LSC) of 84,270 bp, a small single-copy region (SSC) of 17,918 bp and two copies of inverted repeat (IR) regions of 26,491 bp. The overall GC content of C. lyrata is 36.2%. The genome of C. lyrata contains 131 genes, including 85 protein-coding genes (PCGs), 37 tRNAs, and 8 rRNAs. Phylogenetic analysis suggested that the ten species in Cardamine were clustered together into a single branch within the Brassicaceae family and C. amariformis is at the base of the tree and C. lyrata and C. fallax are sister groups of the inner clade.

Maesa hupehensis Rehd 1916 is mainly planted in Hubei and Sichuan. In this study, we assembled and characterized the complete chloroplast genome of M. hupehensis as resources for the future study. The chloroplast genome was 157,005 bp in length, with 37.3% GC content, composing of one large single copy (87,628 bp) and one small single copy (18,111 bp), separated by two inverted repeats (25,633 bp). A total of 130 genes were predicted, including 8 rRNAs, 37 tRNAs, and 84 protein-coding genes. Phylogenetic analysis showed that M. hupehensis was closely related to Maesa montana.

Summary: We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

There are more than 100 GDSL lipases in Arabidopsis, but only a few members have been functionally investigated. Moreover, no reports have ever given a comprehensive analysis of GDSLs in stomatal biology. Here, we systematically investigated the expression patterns of 19 putative Guard-cell-enriched GDSL Lipases (GGLs) at various developmental stages and in response to hormone and abiotic stress treatments. Gene expression analyses showed that these GGLs had diverse expression patterns. Fifteen GGLs were highly expressed in guard cells, with seven preferentially in guard cells. Most GGLs were localized in endoplasmic reticulum, and some were also localized in lipid droplets and nucleus. Some closely homologous GGLs exhibited similar expression patterns at various tissues and in response to hormone and abiotic stresses, or similar subcellular localization, suggesting the correlation of expression pattern and biological function, and the functional redundancy of GGLs in plant development and environmental adaptations. Further phenotypic identification of ggl mutants revealed that GGL7, GGL14, GGL22, and GGL26 played unique and redundant roles in stomatal dynamics, stomatal density and morphology, and plant water relation. The present study provides unique resources for functional insights into these GGLs to control stomatal dynamics and development, plant growth, and adaptation to the environment.

Abnormal metabolism serves a critical role in glioblastoma (GBM). Biochanin A (BCA), a flavonoid phenolic compound found in edible and herbal plants, has antioxidative and antitumor activities. However, it remains unclear whether BCA has an effect on energy metabolism. The aim of the present study was to evaluate the anticancer effects and molecular mechanism of the effect of BCA on energy metabolism. We observed that BCA inhibited the growth of U251 cells by the mitochondria-mediated intrinsic apoptotic pathway. BCA treatment reduced metabolic function, repressed mitochondrial membrane potential, and increased the production of reactive oxygen species (ROS) in GBM. In addition, we found that BCA decreased aerobic glycolysis by inactivation of the AKT/mTOR pathway. Taken together, the results demonstrate that treatment with BCA inhibited the proliferation of GBM by regulating metabolic reprogramming.

Despite the expansion of PD-1 checkpoint blockade to multiple types of cancer, whether the programmed cell death 1 (PD-1) expression status on CD8+ tumour infiltrating lymphocytes (TILs) could be a prognostic factor in cervical cancer is still unclear. In this study, we performed ex vivo phenotypic analysis of PD-1 expression on CD8+ TILs by flow cytometry from 47 treatment-naïve cervical cancer patients. With a median follow-up of 26.1 months (95% confidence interval [CI], 24-28.2 months), we then linked the quantitative cellular expression results to progression-free survival and overall survival. Based on the intensity of PD-1 expression, we further categorised the cervical cancer patients into PD-1high expressers (29.8%, 14/47) and PD-1low expressers (70.2%, 33/47). Multivariate analysis revealed that PD-1high expressers are correlated with early recurrence (HR, 5.91; 95% CI, 1.03-33.82; P= 0.046). Univariate analysis also demonstrated that PD-1high expressers are associated with poor overall survival in cervical cancer (HR, 5.365; 95% CI, 1.55-18.6; P=0.008). Moreover, our study also demonstrated that CD8+/CD4+ TIL ratio and HPV infection status are risk factors for early relapse and mortality in cervical cancer patients. In conclusion, this study confirms that PD-1 expression status is an independent prognostic factor for progression free survival in cervical cancer. These findings could be important in predicting the relapse of cervical cancer as a cellular diagnosis method and could be important knowledge for the selection of prospective PD-1 blockade candidates.

Rotor tracking control, which can be implemented by active magnetic bearing (AMB) system with high precision, can realize many functions, such as attitude control and special surface processing. However, large-motion rotor tracking control is difficult to implemented, due to AMB's highly nonlinear characteristics. In this paper, a dual-loop neural network sliding mode control (DL-NNSMC) system of AMB is proposed for rotor radial tracking control. The complete model of the AMB system is established and the dual-loop control system is designed. A circuit model that considers the rotor motion is established and the model-based inner loop of current control is established, conjointly for dealing with the influence of rotor motion on the current response and the unknown characteristics of the power amplifier. In the outer loop, a nonlinear electromagnetic force model is applied and a wavelet neural network sliding mode control algorithm is designed for accurate position control. Two cases of rotor trajectory tracking are simulated, and the simulation results demonstrate the validity of the proposed control system for large-motion rotor tracking control and its far superior control performance in terms of precision compared with common approaches based on sliding mode control (SMC).

Brassica napus L. has become one of the most important oil-bearing crops, and drought stress severely influences its yield and quality. By combining physio-biochemical characterization and transcriptome analysis, we studied the response of B. napus plants to different degrees of drought stress. Some physio-biochemical traits, such as fresh weight (FW), dry weight (DW), abscisic acid (ABA) content, net photosynthetic rate (Pn), stomatal conductance (gs), and transpiration rate (Tr), were measured, and the total content of the epidermal wax/cutin, as well as their compositions, was determined. The results suggest that both stomatal transpiration and cuticular transpiration are affected when B. napus plants are subjected to varying degrees of drought stress. A total of 795 up-regulated genes and 1050 down-regulated genes were identified under severe drought stress by transcriptome analysis. Gene ontology (GO) enrichment analysis of differentially expressed genes (DEGs) revealed that the up-regulated genes were mainly enriched in the stress response processes, such as response to water deprivation and abscisic acid, while the down-regulated genes were mainly enriched in the chloroplast-related parts affecting photosynthesis. Moreover, overexpression of BnaA01.CIPK6, an up-regulated DEG, was found to confer drought tolerance in B. napus. Our study lays a foundation for a better understanding of the molecular mechanisms underlying drought tolerance in B. napus.

Both sodium alginate and polyethyleneimine (PEI) have a good ability to adsorb heavy metal ions. PEI and sodium alginate were used as important precursors to synthesize positively charged carbon nanoparticles (p-CNDs) with hydroxyl and carboxyl, and negatively charged carbon nanoparticles (n-CNDs) with amino, respectively. The carbon nanoparticles (CNDs) aerogel with a large specific surface area and rich functional groups were constructed by self-assembled p-CNDs and n-CNDs via electrostatic attraction for adsorption of heavy metal ions in water. The results show that CNDs aerogel has good adsorption properties for Pb2+ (96%), Cu2+ (91%), Co2+ (86%), Ni2+ (82%), and Cd2+ (78%). Furthermore, the fluorescence emission intensity of CNDs aerogel will gradually decrease with the increase in the adsorption rate, indicating that it can detect the adsorption process synchronously. In addition, the cytotoxicity test reveals that CNDs have good biocompatibility and will not cause secondary damage to biological cells.

ObjectivesPatients with malignant pleural mesothelioma (MPM) or pleural metastases often present with malignant pleural effusion (MPE). This study aimed to analyze the effect of pleural fluid on cancer cells.Materials and MethodsEstablished patient-derived cancer cell cultures derived from MPE (MPM, breast carcinoma, lung adenocarcinoma) were seeded in 100% pleural fluid (exudate MPM MPE, transudate MPE, non-MPE transudate fluid) and proliferation was monitored. In addition, the establishment of new MPM cell cultures, derived from MPE specimens, was attempted by seeding the cells in 100% MPE fluid.ResultsAll established cancer cell cultures proliferated with similar growth rates in the different types of pleural fluid. Primary MPM cell culture success was similar with MPE fluid as with full culture medium.ConclusionsPleural fluid alone is adequate for cancer cell proliferation in vitro, regardless of the source of pleural fluid. These results support the hypothesis that pleural fluid has important pro-growth biological properties, but the mechanisms for this effect are unclear and likely not malignant effusion specific.

Systemic inflammatory diseases are a heterogeneous family of autoimmune chronic inflammatory disorders that affect multiple systems within the human body. Connective tissue disease (CTD) is a large group within this family characterised by immune-mediated inflammation of the connective tissue. This group of disorders are often associated with pleural manifestations. CTD-induced pleuritis exhibits a wide variety of symptoms and signs including exudative pleural effusions and chest pain. Accurate estimation of prevalence for CTD-related pleuritis is challenging as small effusions are asymptomatic and remain undetected. Rheumatoid arthritis and systemic lupus erythematosus are frequent CTDs and present with pleural pathology in approximately 5–20% and 17–60% of cases, respectively. By contrast, pleural involvement in systemic sclerosis, eosinophilia–myalgia syndrome, mixed connective tissue disease, ankylosing spondylitis, polymyositis and dermatomyositis syndrome is rare. Clinical management depends on the severity of symptoms; however, most effusions resolve spontaneously. In this review we discuss the pathophysiological mechanisms and the clinical considerations of CTD-induced pleuritis.

Interferon gamma (IFNγ) supports effector responses of CD8+ cytotoxic T lymphocytes (CTLs) and is a surrogate marker for detection of antigen-specific T cells. Here, we show that tumor-specific CTL clones have impaired IFNγ expression and production upon activation. Assessment of the relationship between IFNγ production and the 5′methylcytosine-guanine (CpG) dinucleotide methylation of the IFNγ promoter using bisulfite treatment has shown that IFNγ− CTL clones accumulates CpG hypermethylation within the promoter at key transcription factor binding sites (−186 and −54), known to be vital for transcription. We confirmed these findings using ex vivo isolated and short-term expanded bulk tumor-specific CTL lines from four cancer patients and demonstrated that IFNγ methylation inversely correlates with transcription, protein level, and cytotoxicity. Altogether, we propose that a sizeable portion of human tumor-specific CTLs are deficient in IFNγ response, contributed by CpG hypermethylation of the IFNγ promoter. Our findings have important implications for immunotherapy strategies and for methods to detect human antigen-specific T cells.

Abstract Background Cervical cancer is attributable to human papilloma virus (HPV) infection in the majority cases. E1, an HPV derived-protein, plays an important role in the initiation and development of cervical cancer. Our study aims to investigate the HPV E1-specific T cell response in patients with cervical squamous cell carcinoma (CSCC). Methods A total of 66 CSCC patients with FIGO stage IIB-IIIB and 60 healthy controls were enrolled. Enzyme-Linked ImmunoSpot (ELISPOT) assays was used to measure the HPV E1-specific T cell response in the peripheral blood of these patients before treatment. The patients were treated with chemotherapy and/or radiotherapy and followed up clinically for three years. The relationship between the T cell response, various clinical characteristics and the prognosis were studied with univariate analysis, multivariate analysis and survival curve analysis. Results The frequency of HPV E1-specific T cell response in peripheral blood of cervical cancer patients was 59.09%, with mean response intensity 24.56 SFC/106 PBMCs. The frequency and intensity of HPV E1-specific T cell response in patients were higher than healthy controls(p