Mechanism of EBV inducing anti-tumour immunity and its therapeutic use.

Tumour-associated antigens (TAAs) comprise a large set of non-mutated cellular antigens recognized by T cells in human and murine cancers. Their potential as targets for immunotherapy has been explored for more than two decades1, yet the origins of TAA-specific T cells remain unclear. While tumour cells may be an important source of TAAs for T cell priming2, several recent studies suggest that infection with some viruses, including Epstein-Barr virus and influenza virus can elicit T cell responses against abnormally expressed cellular antigens that function as TAAs3,4. However, the cellular and molecular basis of such responses remains undefined. Here we show that expression of the Epstein-Barr virus signalling protein LMP1 in B cells provokes T cell responses to multiple TAAs. LMP1 signalling leads to overexpression of many cellular antigens previously shown to be TAAs, their presentation on major histocompatibility complex classes I (MHC-I) and II (MHC-II) (mainly through the endogenous pathway) and the upregulation of costimulatory ligands CD70 and OX40L, thereby inducing potent cytotoxic CD4+ and CD8+ T cell responses. These findings delineate a mechanism of infection-induced anti-tumour immunity. Furthermore, by ectopically expressing LMP1 in tumour B cells from patients with cancer and thereby enabling them to prime T cells, we develop a general approach for rapid production of autologous cytotoxic CD4+ T cells against a wide range of endogenous tumour antigens, such as TAAs and neoantigens, for treating B cell malignancies. This work stresses the need to revisit classical concepts concerning viral and tumour immunity, which will be critical to fully understand the impact of common infections on human health and to improve the rational design of immune approaches to treatment of cancers.

A dual RNA-seq analyses revealed dynamic arms race during the invasion of walnut by Colletotrichum gloeosporioides.

BACKGROUND: Walnut anthracnose caused by Colletotrichum gloeosporioides seriously endangers the yield and quality of walnut, and has now become a catastrophic disease in the walnut industry. Therefore, understanding both pathogen invasion mechanisms and host response processes is crucial to defense against C. gloeosporioides infection. RESULTS: Here, we investigated the mechanisms of interaction between walnut fruits (anthracnose-resistant F26 fruit bracts and anthracnose-susceptible F423 fruit bracts) and C. gloeosporioides at three infection time points (24hpi, 48hpi, and 72hpi) using a high-resolution time series dual transcriptomic analysis, characterizing the arms race between walnut and C. gloeosporioides. A total of 20,780 and 6670 differentially expressed genes (DEGs) were identified in walnut and C. gloeosporioides against 24hpi, respectively. Generous DEGs in walnut exhibited opposite expression patterns between F26 and F423, which indicated that different resistant materials exhibited different transcriptional responses to C. gloeosporioides during the infection process. KEGG functional enrichment analysis indicated that F26 displayed a broader response to C. gloeosporioides than F423. Meanwhile, the functional analysis of the C. gloeosporioides transcriptome was conducted and found that PHI, SignalP, CAZy, TCDB genes, the Fungal Zn (2)-Cys (6) binuclear cluster domain (PF00172.19) and the Cytochrome P450 (PF00067.23) were largely prominent in F26 fruit. These results suggested that C. gloeosporioides secreted some type of effector proteins in walnut fruit and appeared a different behavior based on the developmental stage of the walnut. CONCLUSIONS: Our present results shed light on the arms race process by which C. gloeosporioides attacked host and walnut against pathogen infection, laying the foundation for the green prevention of walnut anthracnose.

JrWRKY21 interacts with JrPTI5L to activate the expression of JrPR5L for resistance to Colletotrichum gloeosporioides in walnut.

Walnut (Juglans regia L.) anthracnose, induced by Colletotrichum gloeosporioides, is a catastrophic disease impacting the walnut industry in China. Although WRKY transcription factors play a key role in plant immunity, the function of the WRKY gene family in walnut resistance to C. gloeosporioides is not clear. Here, through transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR), we identified a differentially expressed gene, JrWRKY21, that was significantly upregulated upon C. gloeosporioides infection in walnut. JrWRKY21 positively regulated walnut resistance to C. gloeosporioides, as demonstrated by virus-induced gene silencing and transient gene overexpression. Additionally, JrWRKY21 directly interacted with the transcriptional activator of the pathogenesis-related (PR) gene JrPTI5L in vitro and in vivo, and could bind to the W-box in the JrPTI5L promoter for transcriptional activation. Moreover, JrPTI5L could induce the expression of the PR gene JrPR5L through binding to the GCCGAC motif in the promoter. Our data support that JrWRKY21 can indirectly activate the expression of the JrPR5L gene via the WRKY21-PTI5L protein complex to promote resistance against C. gloeosporioides in walnut. The results will enhance our understanding of the mechanism behind walnut disease resistance and facilitate the genetic improvement of walnut by molecular breeding for anthracnose-resistant varieties.

The disinhibition effect of iron-based particles on anaerobic digestion of florfenicol-containing cow manure: Performance and mechanism.

The overuse of antibiotics has caused problems such as environmental pollution, increased antibiotic resistance of pathogenic bacteria, and inhibition of engineered microbial processes such as anaerobic digestion (AD). At present, mitigating the inhibition of antibiotics on the process of microbial recycling of organic matter by using additives has always been a research hotspot. In this study, the effects of the addition of three iron-based particles including zero-valent iron (ZVI), Fe2O3 and Fe3O4 on the biogas yield during the AD of cow manure containing florfenicol (FLO) were studied. It was found that by alleviating the acid accumulation, the addition of low-concentration ZVI, Fe2O3 and high-concentration Fe3O4 enhanced the maximum methane production rate of FLO-containing cow manure during AD to 3.5, 1.7 and 3.6 times, respectively, while high concentration of ZVI will lead to the crash of the AD system due to the rise of pH. Within the concentration range of iron-based particles dosed in this study, the Fe3O4 dosage showed a significant positive correlation with the cumulative methane production enhancement rate (p < 0.01). The sum of the relative abundances of Limnobacter and Pseudomonas was correlated with the absolute abundance of floR gene with the Pearson correlation coefficient of 0.9457 (p < 0.01), indicating the possibility of these two genera being the potential host bacteria for floR gene.

The role of hydrochloric acid pretreated activated carbon in chain elongation of D-lactate to caproate: Adsorption and facilitation.

Medium chain fatty acids (MCFA) generation is attracting growing interest due to fossil fuel depletion. To promote the production of MCFA, especially caproate, hydrochloric acid pretreated activated carbon (AC) was introduced into chain elongation fermentation. In this study, the role of pretreated AC on caproate production was investigated using lactate and butyrate as electron donor and electron acceptor, respectively. The results showed that AC did not improve the chain elongation reaction at beginning but promoted the caproate production at later stage. The addition of 15 g/L AC facilitated reactor reaching the peak of caproate concentration (78.92 mM), caproate electron efficiency (63.13%), and butyrate utilization rate (51.88%). The adsorption experiment revealed a positive correlation between the adsorption capacity of pretreated AC and the concentration as well as the carbon chain length of carboxylic acids. Moreover, the adsorption of undissociated caproate by pretreated AC contributed to a mitigated toxicity towards microorganisms, thereby facilitating the production of MCFA. Microbial community analysis revealed an increasing enrichment of key functional chain elongation bacteria, including Eubacterium, Megasphaera, Caproiciproducens, and Pseudoramibacter, but a suppression on acrylate pathway microorganism Veillonella, as the dosage of pretreated AC increasing. The findings of this study demonstrated the substantial impact of the adsorption effect of acid-pretreated AC on promoting caproate production, which would aid to the development of more efficient caproate production process.

A retrospective case-control study of facial emotion recognition in male veterans with chronic schizophrenia and its correlation with interpersonal communication.

OBJECTIVE: To understand the facial emotion recognition of male veterans with chronic schizophrenia and the relationship between facial emotion recognition and interpersonal communication to provide a reference for designing social skills training programmes. METHOD: Fifty-six eligible male patients with chronic schizophrenia who were admitted to our hospital from October 2020 to April 2021 were selected, and 24 healthy people were selected as controls. Facial emotion recognition, social communication skills and self-perceived interpersonal disturbance were assessed using a facial emotion recognition stimulus manual, the Social Skills Checklist (SSC) and the Interpersonal Relationship Integrative Diagnostic Scale (IRIDS). Disease status was assessed using the Positive and Negative Syndrome Scale. RESULTS: Both the control group and the patient group had the highest recognition accuracy for neutral faces. The recognition rate for neutral expression was higher in the control group than in the patient group (p = 0.008). The rate of neutral expressions identified as happiness was higher in the patient group than in the control group (p = 0.001). The identification of anger as happiness was higher in the control group than in the patient group (p = 0.026), and the pattern of misidentification was similar between the control group and the patient group. The accuracy of facial emotion recognition was negatively associated with the age of onset (p < 0.05). The recognition accuracy for happiness was negatively associated with negative symptoms, general pathological symptoms and total scale scores (p < 0.05). The total score for expression recognition was negatively associated with the negative symptom subscale scores (p < 0.05), and there was no correlation between expression recognition and positive symptoms (p > 0.05). The recognition accuracy for happiness was negatively correlated with the IRIDS conversation factor (p < 0.05). The recognition accuracy for happiness and anger and the total scores for facial emotion recognition were negatively correlated with the SSC subscale score and the total score (p < 0.05 and p < 0.01, respectively). The main influencing factors on facial emotion recognition were the SSC total score (p < 0.001) and the positive factor score (p = 0.039). CONCLUSION: Veterans with chronic schizophrenia have facial emotion recognition impairments affected by negative symptoms. There is a correlation between facial emotion recognition and interpersonal communication. HIGHLIGHTS: 1. There are extensive facial expression recognition disorders in schizophrenia. 2. The pattern of misidentification was similar in both the control group and the patient group, with the tendency for happiness to be identified as a neutral emotion, anger as happiness, and fear as neutral emotion and anger. 3. Based on the comprehensive assessment of social cognitive impairment in patients with schizophrenia, prospective studies of standardised interventions are designed to provide support for clinical practice.

Combined Detection of IFN-γ and Lymphocyte Subsets with Activation Indicators in the Clinical Application of Mycobacterium Tuberculosis Infection at Different Times.

The immune status of mycobacterium tuberculosis (MTB) infection is essential for the diagnosis and treatment of this disease. In this work, we aim to evaluate the clinical significance of the combination of serum IFN-γ, IGRAs (Interferon-Gamma Release Assay), lymphocyte subset with activation indicators detection in active and latent tuberculosis infection patients. For this study, anticoagulant whole blood were collected from 45 active tuberculosis (AT group), 44 latent tuberculosis (LT group) and 32 healthy controls (HCs group). The serum IFN-γ and IGRAs detected by chemiluminescence, and the percentage of lymphocyte subsets and activated lymphocytes detected by flow cytometry. The results showed combined IGRAs, serum IFN-γ and NKT cells not only has good diagnostic efficiency for the AT, but also provides a laboratory diagnostic method to distinguish AT from LT. Activation indicator of CD3+HLA-DR+T and CD4+HLA-DR+T can effectively distinguish LT from HCs. While combined CD3+T, CD4+T, CD8+CD28+T, Treg and CD16+CD56+CD69+ cells can distinguish AT from HCs. This study showed combined direct detection of serum IFN-γ and IGRAs as well as lymphocyte subsets with activation indicators which may provide laboratory basis for the diagnosis and differential diagnosis of active and latent MTB infection.

Redox mediators stimulated chain elongation process in fluidized cathode electro-fermentation systems for caproate production.

Medium chain fatty acids (MCFAs), the secondary products of traditional anaerobic fermentation, can be produced via chain elongation (CE), a process often retarded due to the difficulty during interspecies electron transfer (IET). This study employed redox mediators, neutral red (NR), methyl viologen (MV), and methylene blue (MB) as electron shuttles to expedite the electro-fermentation for caproate production by improving IET. Results showed that MV increased the MCFAs production by promoting acetate to ethanol conversion, leading to the highest MCFAs selectivity of 68.73%. While NR was indicated to improve CE by encouraging H2 production, and the biocathode had the highest electrical activity due to the smallest internal resistance and largest capacitance increase of 96% than the control. A higher proportion of Sutterella, Prevotella, and Hydrogenophaga, linked with the H2 mediated interspecies electron transfer (MIET) during CE process, was observed across redox mediators supplied groups compared to the control. The presence of mediators led to an elevated abundance of key enzymes for enhanced CE process and electron transfer. This study provided the perspective of the stimulated electron transfer for improved MCFAs production in electro-fermentation systems.

Construction of α,ß-Diamino Diacid Derivatives with Adjacent Acyclic Tetrasubstituted Stereocenters.

A convenient strategy for the diastereoselective synthesis of α,ß-diamino diacid derivatives bearing congested vicinal acyclic tetrasubstituted stereocenters via catalytic Mannich-type reactions of azlactones and 2-aminoacrylates was established. A diverse set of α,ß-diamino diacid derivatives were synthesized in good to excellent yields and diastereoselectivities. Good enantioselectivity (up to 98:2 er) was achieved by employing the catalyst (DHQD)2PHAL in the subsequent asymmetric study.

PAK5 is a potential target in myelodysplastic syndrome through interacting with LMO2 and GATA1.

Myelodysplastic syndrome (MDS) is a neoplastic heterogeneous and pre-leukemic disease with poor clinical outcome due to the failure of current chemotherapeutic strategies to target leukemic stem cells. Recently, we find that p21-activated kinase 5 (PAK5) overexpresses in MDS patients and leukemia cell lines. The clinical and prognostic value of PAK5 in MDS is unclear although it has anti-apoptosis ability and can promote cell survival and mobility in solid tumors. In this study, we find that LMO2 is co-expressed with PAK5 in the aberrant cells from MDS, and mitochondria-localized PAK5 can translocate into cell nucleus upon fetal bovine serum stimulation to interact with LMO2 and GATA1, which are important transcription regulators in hematological malignancies. Interestingly, without LMO2, PAK5 fails to bind GATA1 and facilitate GATA1 Ser161 site phosphorylation, indicating that PAK5 may be a key kinase in LMO2-associated hematopoietic diseases. Moreover, we find that PAK5 protein level in MDS is significantly higher than leukemia, and the data of 2095 leukemia samples from 'BloodSpot' database shows that PAK5 mRNA level in MDS is also increased obviously. Taken together, our findings suggest that PAK5-targeted strategies in clinical therapy have a potential value on MDS intervention.

Modified biochar improves the storage capacity and adsorption affinity of organic phosphorus in soil.

The loss of soil organic phosphorus can easily cause water eutrophication. In order to effectively reduce the loss of soil organic phosphorus, this manuscript investigated the adsorption of soil organic phosphorus by lanthanum modified biochar (BC), traditional adsorbent gypsum (GY) and zeolite (ZE) by taking phytic acid as the representative. The adsorption isotherm model and kinetic models were used to fit the phosphorus absorption characteristics of the adsorbents. The effects of initial pH and temperature on the adsorption capacity were discussed, and the adsorption mechanism of each adsorbent was explained by means of FTIR and XRD. The results showed that the adsorption capacity of phytate phosphorus followed the trend of BCTS > GYTS > ZETS > TS (soil), and the maximum phosphorus adsorption capacity obtained from Langmuir isotherm for treatment with BCTS was 2.836 mg g-1, and the treatment had the strongest affinity for phytate phosphorus and also the ability to store phosphorus. The adsorption process fits well with Langmuir isotherm equation and pseudo-second-order kinetic equation, and the adsorption behavior of phytate phosphorus was mainly controlled by the chemisorption of monolayer. When the concentration of phytate phosphorus was 100 mg L-1, percentage of modified biochar added to the soil was 3% and the pH was 6, the adsorption capacity reached the maximum, and the maximum adsorption capacity was 2.000 mg g-1. The results of FTIR and XRD characterization showed that complexation was the main adsorption mechanism. In this study, the combination of modified biochar and soil phytate phosphorus can provide a good theoretical basis for reducing the loss of soil organic phosphorus.

What is the impact of perioperative cerebral oxygen desaturation on postoperative delirium in old population: a systemic review and meta-analysis.

BACKGROUND: Perioperative cerebral oxygen saturation (ScO2) has been reported to associate with postoperative delirium (POD) which is a common postoperative complication, however, the results were inconclusive. Therefore, we aimed to conduct an up-to-date review and meta-analyze the relationship between perioperative ScO2 and POD. METHODS: We systematically searched PubMed, Embase and Web of science through January 13, 2022. The pooled results were estimated through a random-effects model meta-analysis and expressed as odds ratios (ORs) and standard mean differences (SMDs), accompanied with 95% confident intervals (CIs). RESULTS: Finally, of 467 searched articles, ten articles were included. A total of six studies reported the baseline ScO2 value and the pooled result showed that preoperative baseline ScO2 was lower in POD groups (SMD = - 0.41, 95% CI - 0.64 to - 0.18). And beyond that, the pooled OR across four literatures about preoperative low ScO2 on POD was 3.44 (95% CI 1.69, 7.02). In contrast, insignificant differences were detected in baseline/lowest ScO2 value during intraoperative and postoperative period. Additionally, there were no statistically significant associations for intraoperative and postoperative low ScO2 effect on POD risk. Meta-regress analysis has found no significant impact factors. CONCLUSIONS: Based on current evidence, POD patients have a lower ScO2, and ScO2 desaturation may increase POD incidence, indicating the role of ScO2 underlying pathological mechanisms. For generalizability of evidence, we should rely on high-quality, considering more comprehensively longitudinal, interdisciplinary studies.

Genome-wide identification and characterization of long non-coding RNAs conferring resistance to Colletotrichum gloeosporioides in walnut (Juglans regia).

BACKGROUND: Walnut anthracnose caused by Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. is an important walnut production problem in China. Although the long non-coding RNAs (lncRNAs) are important for plant disease resistance, the molecular mechanisms underlying resistance to C. gloeosporioides in walnut remain poorly understood. RESULTS: The anthracnose-resistant F26 fruits from the B26 clone and the anthracnose-susceptible F423 fruits from the 4-23 clone of walnut were used as the test materials. Specifically, we performed a comparative transcriptome analysis of F26 and F423 fruit bracts to identify differentially expressed LncRNAs (DELs) at five time-points (tissues at 0 hpi, pathological tissues at 24 hpi, 48 hpi, 72 hpi, and distal uninoculated tissues at 120 hpi). Compared with F423, a total of 14,525 DELs were identified, including 10,645 upregulated lncRNAs and 3846 downregulated lncRNAs in F26. The number of upregulated lncRNAs in F26 compared to in F423 was significantly higher at the early stages of C. gloeosporioides infection. A total of 5 modules related to disease resistance were screened by WGCNA and the target genes of lncRNAs were obtained. Bioinformatic analysis showed that the target genes of upregulated lncRNAs were enriched in immune-related processes during the infection of C. gloeosporioides, such as activation of innate immune response, defense response to bacterium, incompatible interaction and immune system process, and enriched in plant hormone signal transduction, phenylpropanoid biosynthesis and other pathways. And 124 known target genes for 96 hub lncRNAs were predicted, including 10 known resistance genes. The expression of 5 lncRNAs and 5 target genes was confirmed by qPCR, which was consistent with the RNA-seq data. CONCLUSIONS: The results of this study provide the basis for future functional characterizations of lncRNAs regarding the C. gloeosporioides resistance of walnut fruit bracts.

Transcriptome and proteome analysis of walnut (Juglans regia L.) fruit in response to infection by Colletotrichum gloeosporioides.

BACKGROUND: Walnut anthracnose induced by Colletotrichum gloeosporioides is a disastrous disease affecting walnut production. The resistance of walnut fruit to C. gloeosporioides is a highly complicated and genetically programmed process. However, the underlying mechanisms have not yet been elucidated. RESULTS: To understand the molecular mechanism underlying the defense of walnut to C. gloeosporioides, we used RNA sequencing and label-free quantitation technologies to generate transcriptomic and proteomic profiles of tissues at various lifestyle transitions of C. gloeosporioides, including 0 hpi, pathological tissues at 24 hpi, 48 hpi, and 72 hpi, and distal uninoculated tissues at 120 hpi, in anthracnose-resistant F26 fruit bracts and anthracnose-susceptible F423 fruit bracts, which were defined through scanning electron microscopy. A total of 21,798 differentially expressed genes (DEGs) and 1929 differentially expressed proteins (DEPs) were identified in F26 vs. F423 at five time points, and the numbers of DEGs and DEPs were significantly higher in the early infection stage. Using pairwise comparisons and weighted gene co-expression network analysis of the transcriptome, we identified two modules significantly related to disease resistance and nine hub genes in the transcription expression gene networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the DEGs and DEPs revealed that many genes were mainly related to immune response, plant hormone signal transduction, and secondary metabolites, and many DEPs were involved in carbon metabolism and photosynthesis. Correlation analysis between the transcriptome data and proteome data also showed that the consistency of the differential expression of the mRNA and corresponding proteins was relatively higher in the early stage of infection. CONCLUSIONS: Collectively, these results help elucidate the molecular response of walnut fruit to C. gloeosporioides and provide a basis for the genetic improvement of walnut disease resistance.

Illuminating Key Microbial Players and Metabolic Processes Involved in the Remineralization of Particulate Organic Carbon in the Ocean's Twilight Zone by Metaproteomics.

The twilight zone (from the base of the euphotic zone to the depth of 1,000 m) is the major area of particulate organic carbon (POC) remineralization in the ocean, and heterotrophic microbes contribute to more than 70% of the estimated remineralization. However, little is known about the microbial community and metabolic activity directly associated with POC remineralization in this chronically understudied realm. Here, we characterized the microbial community proteomes of POC samples collected from the twilight zone of three contrasting sites in the Northwest Pacific Ocean using a metaproteomic approach. The particle-attached bacteria from Alteromonadales, Rhodobacterales, and Enterobacterales were the primary POC remineralizers. Hydrolytic enzymes, including proteases and hydrolases, that degrade proteinaceous components and polysaccharides, the main constituents of POC, were abundant and taxonomically associated with these bacterial groups. Furthermore, identification of diverse species-specific transporters and metabolic enzymes implied niche specialization for nutrient acquisition among these bacterial groups. Temperature was the main environmental factor driving the active bacterial groups and metabolic processes, and Enterobacterales replaced Alteromonadales as the predominant group under low temperature. This study provides insight into the key bacteria and metabolic processes involved in POC remineralization, and niche complementarity and species substitution among bacterial groups are critical for efficient POC remineralization in the twilight zone. IMPORTANCE The ocean's twilight zone is a critical zone where more than 70% of the sinking particulate organic carbon (POC) is remineralized. Therefore, the twilight zone determines the size of biological carbon storage in the ocean and regulates the global climate. Prokaryotes are major players that govern remineralization of POC in this region. However, knowledge of microbial community structure and metabolic activity is still lacking. This study unveiled microbial communities and metabolic activities of POC samples collected from the twilight zone of three contrasting environments in the Northwest Pacific Ocean using a metaproteomic approach. Alteromonadales, Rhodobacterales, and Enterobacterales were the major remineralizers of POC. They excreted diverse species-specific hydrolytic enzymes to split POC into solubilized POC or dissolved organic carbon. Temperature played a crucial role in regulating the community composition and metabolism. Furthermore, niche complementarity or species substitution among bacterial groups guaranteed the efficient remineralization of POC in the twilight zone.

Organocatalytic Asymmetric Synthesis of Benzothiazolopyrimidines via [4 + 2] Cyclization of 2-Benzothiazolimines and Aldehydes.

We report the direct asymmetric synthesis of pyrimido[2,1-b]benzothiazoles using a commercially available chiral amine catalyst. A variety of 2-benzothiazolimines and aldehydes were well tolerated under the reaction conditions and generated the corresponding products in 81-99% yields with excellent diastereoselectivities and enantioselectivities (up to >20:1 dr, 99% ee). Furthermore, the products could be easily converted to other useful chiral building blocks.

Signaling by the Epstein-Barr virus LMP1 protein induces potent cytotoxic CD4+ and CD8+ T cell responses.

The B-lymphotropic Epstein-Barr virus (EBV), pandemic in humans, is rapidly controlled on initial infection by T cell surveillance; thereafter, the virus establishes a lifelong latent infection in the host. If surveillance fails, fatal lymphoproliferation and lymphomagenesis ensue. The initial T cell response consists of predominantly CD8+ cytotoxic T cells and a smaller expansion of CD4+ cells. A major approach to treating EBV-associated lymphomas is adoptive transfer of autologous or allogeneic T cells that are stimulated/expanded on EBV-transformed B cells. Strikingly, the clinical response correlates with the frequency of CD4 cells in the infused T cells. Although in vitro studies suggested that EBV-specific CD4 cells develop cytotoxicity, they have not been comprehensively characterized and the molecular mechanism underlying their formation remains unknown. Our recent work, using a transgenic approach in mice, has revealed a central role for the EBV signaling molecule LMP1 in immune surveillance and transformation of EBV-infected B cells. The mouse model offers a unique tool for uncovering basic features of EBV immunity. Here, we show that LMP1 expression in B cells induces potent cytotoxic CD4 and CD8 T cell responses, by enhancing antigen presentation and costimulation by CD70, OX40 ligand, and 4-1BB ligand. Our data further suggest that cytotoxic CD4 cells hold superior therapeutic value for LMP1 (EBV)-driven lymphomas. These findings provide insights into EBV immunity, demonstrating that LMP1 signaling alone is sufficient to induce a prominent cytotoxic CD4 response, and suggest strategies for immunotherapy in EBV-related and other cancers.

The Influence of Lower Temperature Induction of Valsa mali on the Infection of Apple Trees.

Apple valsa canker (AVC), caused by Valsa mali, is one of the most important diseases of apple trees in China. AVC occurred severely along with cold winter or cold spring. However, the effect of lower temperature on V. mali is poorly understood. This study evaluated the influence of lower temperature pretreatment of V. mali on the infection of apple twigs and leaves. The results showed that exposing V. mali to lower temperatures (between -10°C and 10°C) for more than 18 h significantly increased the disease severity of apple leaves and twigs, with a higher lesion area ratio (LAR), lesion length, and disease incidence (DI) than that at 25°C. In addition, cold treatment ranging from -5°C to 10°C promoted colony growth. Meanwhile, the relative expression of four cell wall degrading enzyme (CWDE)-related genes pretreated at -5°C and 5°C were significantly higher than that at 25°C. The results indicated that the virulence of V. mali mycelium is sensitive to lower temperatures. After sensing lower temperature changes, V. mali can adjust its infection of apple trees by regulating the expression of pathogenicity gene and growth rate. Spring has very frequent temperature changes, and V. mali is highly invasive in this season. Therefore, more attention should be paid in spring to protecting apple trees from infection of V. mali, by reducing pruning wound formation in spring and applying protective agents to pruning wounds in time.

Comparative population genomics reveals genetic divergence and selection in lotus, Nelumbo nucifera.

BACKGROUND: Lotus (Nelumbo nucifera) is an aquatic plant with important agronomic, horticulture, art and religion values. It was the basal eudicot species occupying a critical phylogenetic position in flowering plants. After the domestication for thousands of years, lotus has differentiated into three cultivated types -flower lotus, seed lotus and rhizome lotus. Although the phenotypic and genetic differentiations based on molecular markers have been reported, the variation on whole-genome level among the different lotus types is still ambiguous. RESULTS: In order to reveal the evolution and domestication characteristics of lotus, a total of 69 lotus accessions were selected, including 45 cultivated accessions, 22 wild sacred lotus accessions, and 2 wild American lotus accessions. With Illumina technology, the genomes of these lotus accessions were resequenced to > 13× raw data coverage. On the basis of these genomic data, 25 million single-nucleotide polymorphisms (SNPs) were identified in lotus. Population analysis showed that the rhizome and seed lotus were monophyletic and genetically homogeneous, whereas the flower lotus was biphyletic and genetically heterogeneous. Using population SNP data, we identified 1214 selected regions in seed lotus, 95 in rhizome lotus, and 37 in flower lotus. Some of the genes in these regions contributed to the essential domestication traits of lotus. The selected genes of seed lotus mainly affected lotus seed weight, size and nutritional quality. While the selected genes were responsible for insect resistance, antibacterial immunity and freezing and heat stress resistance in flower lotus, and improved the size of rhizome in rhizome lotus, respectively. CONCLUSIONS: The genome differentiation and a set of domestication genes were identified from three types of cultivated lotus- flower lotus, seed lotus and rhizome lotus, respectively. Among cultivated lotus, flower lotus showed the greatest variation. The domestication genes may show agronomic importance via enhancing insect resistance, improving seed weight and size, or regulating lotus rhizome size. The domestication history of lotus enhances our knowledge of perennial aquatic crop evolution, and the obtained dataset provides a basis for future genomics-enabled breeding.

Injury-preconditioning secretome of umbilical cord mesenchymal stem cells amplified the neurogenesis and cognitive recovery after severe traumatic brain injury in rats.

Traumatic brain injury (TBI) is a dominant cause of death and permanent disability worldwide. Although TBI could significantly increase the proliferation of adult neural stem cells in the hippocampus, the survival and maturation of newborn cells is markedly low. Increasing evidence suggests that the secretome derived from mesenchymal stem cells (MSCs) would be an ideal alternative to MSC transplantation. The successive and microenvironmentally responsive secretion in MSCs may be critical for the functional benefits provided by transplanted MSCs after TBI. Therefore, it is reasonable to hypothesize that the signaling molecules secreted in response to local tissue damage can further facilitate the therapeutic effect of the MSC secretome. To simulate the complex microenvironment in the injured brain well, we used traumatically injured brain tissue extracts to pretreat umbilical cord mesenchymal stem cells (UCMSCs) in vitro and stereotaxically injected the secretome from traumatic injury-preconditioned UCMSCs into the dentate gyrus of the hippocampus in a rat severe TBI model. The results revealed that compared with the normal secretome, the traumatic injury-preconditioned secretome could significantly further promote the differentiation, migration, and maturation of newborn cells in the dentate gyrus and ultimately improve cognitive function after TBI. Cytokine antibody array suggested that the increased benefits of secretome administration were attributable to the newly produced proteins and up-regulated molecules from the MSC secretome preconditioned by a traumatically injured microenvironment. Our study utilized the traumatic injury-preconditioned secretome to amplify neurogenesis and improve cognitive recovery, suggesting this method may be a novel and safer candidate for nerve repair. Cover Image for this issue: doi: 10.1111/jnc.14741.