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Abstract Podocalyxin-like protein (PODXL) is known to originate from tumor cells in several cancers; however, which cell type it is expressed in, whether and how it may contribute to tumor progression after radiotherapy or chemoradiotherapy in cervical cancer (CC) remain unknown. In this study, we investigated these issues using a cohort of 180 immune stain data, single-cell RNA sequencing (scRNA-seq) data of 29,453 cells, and bulk RNA sequencing data from 187 cervical cancer samples treated with radiotherapy or chemoradiotherapy. ScRNA-seq analysis revealed that PODXL was predominantly expressed in tumor endothelial cells (TECs) of CC, which was corroborated by tumor section staining. Moreover, the PODXL expression level was negatively associated with progression-free survival and overall survival of 180 CC patients receiving radiotherapy or chemoradiotherapy (both p

Abstract Tissue-resident memory T cells (TRMs) play a critical role in cancer immunity by offering quick and effective immune responses. However, the cellular heterogeneity of TRMs and their significance in cervical cancer (CC) remain unknown. In this study, we generated and analyzed single-cell RNA sequencing data from 12,945 TRMs (ITGAE + CD3D + ) and 25,627 non-TRMs (ITGAE − CD3D + ), derived from 11 CC tissues and 5 normal cervical tissues. We found that TRMs were more immunoreactive than non-TRMs, and TRMs in CC tissues were more activated than those in normal cervical tissues. Six CD8+ TRM subclusters and one CD4+ TRM subcluster were identified. Among them, CXCL13 + CD8+ TRMs were more abundant in CC tissues than in normal cervical tissues, had both cytotoxic and inhibitory features, and were enriched in pathways related to defense responses to the virus. Meanwhile, PLAC8 + CD8+ TRMs were less abundant in CC tissues than in normal cervical tissues but had highly cytotoxic features. The signature gene set scores of both cell subclusters were positively correlated with the overall survival and progression-free survival of patients with CC following radiotherapy. Of note, the association between HLA-E and NKG2A, either alone or in a complex with CD94, was enriched in CXCL13 + CD8+ TRMs interacting with epithelial cells at CC tissues. The in-depth characterization of TRMs heterogeneity in the microenvironment of CC could have important implications for advancing treatment and improving the prognosis of patients with CC.

RNA modifications are epigenetic changes that alter the structure and function of RNA molecules, playing a crucial role in the onset, progression, and treatment of cancer. Immune checkpoint inhibitor (ICI) therapies, particularly PD-1 blockade and anti-CTLA-4 treatments, have changed the treatment landscape of virous cancers, showing great potential in the treatment of different cancer patients, but sensitivity to these therapies is limited to certain individuals. This review offers a comprehensive survey of the functions and therapeutic implications of the four principal RNA modifications, particularly highlighting the significance of m6A in the realms of immune cells in tumor and immunotherapy. This review starts by providing a foundational summary of the roles RNA modifications assume within the immune cell community, focusing on T cells, NK cells, macrophages, and dendritic cells. We then discuss how RNA modifications influence the intricate regulatory mechanisms governing immune checkpoint expression, modulation of ICI efficacy, and prediction of ICI treatment outcomes, and review drug therapies targeting genes regulated by RNA modifications. Finally, we explore the role of RNA modifications in gene editing, cancer vaccines, and adoptive T cell therapies, offering valuable insights into the use of RNA modifications in cancer immunotherapy.

Scientific knowledge about the ancestral genome of core eudicot plant kingdom can potentially have profound impacts on both basic and applied research, including evolution, genetics, genomics, ecology, agriculture, forestry, and global climate. To investigate which plant conserves best the core eudicots common ancestor genome, we compared Arcto-Tertiary relict Nyssaceae and 30 other eudicot plant families. The genomes of Davidia involucrata (a known living fossil), Camptotheca acuminata and Nyssa sinensis, one per existent genus of Nyssaceae, were performed comparative genomic analysis. We found that Nyssaceae originated from a single Nyssaceae common tetraploidization event (NCT)– autotetraploidization 28–31 Mya after the core eudicot common hexaploidization (ECH). We identified Nyssaceae orthologous and paralogous genes, determined its chromosomal evolutionary trajectory, and reconstructed the Nyssaceae most recent ancestor genome. D. involucrata genome contained the entire seven paleochromosomes and 17 ECH-generated eudicot common ancestor chromosomes and was the slowest in mutation among the analyzed 42 species of 31 plant families. Combing both its high retention of paleochromosomes and its low mutation rate, D. involucrata provides the best case in conservation of the core eudicot paleogenome.

Abstract All‐solid‐state batteries (ASSBs) based on inorganic solid electrolytes fascinate a large body of researchers in terms of overcoming the inferior energy density and safety issues of existing lithium‐ion batteries. To date, the cathode designs in the ASSBs achieve remarkable achievements, adding the urgency of scaling up the battery system toward inorganic solid‐state pouch cell configuration for the application market. Herein, the recent developments of cathode materials and the design considerations for their application in the pouch cell format are reviewed to straighten out the roadmap of ASSBs. Specifically, the intercalation compounds and the conversion materials with conversion chemistries are highlighted and discussed as two potentially valuable material types. This review focuses on the basic electrochemical mechanisms, mechanical contact issues, and sheet‐type structure in inorganic solid‐state pouch cells with corresponding perspectives, thus guiding the future research direction. Finally, the benchmarks for manufacturing inorganic solid‐state pouch cells to meet practical high energy density targets are provided in this review for the development of commercially viable products.

Abstract Longjing Monastery served as a prominent Buddhist center in Hangzhou during the Northern Song Dynasty. Similar to other esteemed Buddhist monasteries and mountains in China, the monastery’s initial prestige owed in part to its mystical associations with the Daoist recluse, Ge Hong. However, to secure sustained acclaim, adept leadership was crucial. Thus, this study delves into the monastery’s popularity during the Northern Song era, highlighting how the legendary abbot Biancai established both a robust personal reputation and monastic success by “making friends in the outside secular world.”

Abstract Tumor-infiltrating T cells recognize, attack, and clear tumor cells, playing a central role in antitumor immune response. However, certain immune cells can impair this response and help tumor immune escape. Therefore, exploring the factors that influence T-cell infiltration is crucial to understand tumor immunity and improve therapeutic effect of cancer immunotherapy. The use of single-cell RNA sequencing (scRNA-seq) allows the high-resolution analysis of the precise composition of immune cells with different phenotypes and other microenvironmental factors, including non-immune stromal cells and the related molecules in the tumor microenvironment of various cancer types. In this review, we summarized the research progress on T-cell infiltration and the crosstalk of other stromal cells and cytokines during T-cell infiltration using scRNA-seq to provide insights into the mechanisms regulating T-cell infiltration and contribute new perspectives on tumor immunotherapy.

Coptis chinensis Franch., also named Chinese goldthread is a member of Ranunculaceae in the order Ranunculales and represents an important lineage of early eudicots with traditional medicinal value. In our study, by using syntenic analysis combined with phylogenomic analysis of C. chinensis and four other representative genomes from basal and core eudicots, we confirmed that the WGD event in C. chinensis was shared by Aquilegia coerulea and Papaver somniferum L. and quickly occurred after Ranunculales diverged from other eudicots, likely a Ranunculales common tetraploidization (RCT). The synonymous nucleotide substitutions at synonymous sites distribution of syntenic blocks across these genomes showed that the evolutionary rate of the P. somniferum genome is faster than that of the C. chinensis genome by approximately 13.7%, possibly due to Papaveraceaes having an additional special tetraploidization event (PST). After Ks correction, the RCT dated to 115–130 million years ago (MYA), which was close to the divergence of Ranunculaceaes and Papaveraceaes approximately 115.45–130.51 MYA. Moreover, we identified homologous genes related to polyploidization and speciation and constructed multiple sequence alignments with different reference genomes. Notably, the event-related subgenomes in the basal genomes all showed genomic fractionation bias, suggesting a likely allopolyploid nature of the RCT, PST and T-Alpha and T-Beta events in Tetracentron sinense. In addition, we detected that the sixteen P450 subfamilies were markedly expanded in the genomes of Ranunculales, and most of them were related to the RCT and PST events. We constructed a new platform for Early Eudicot Comparative Genomic Research (http://www.cgrpoee.top/index.html) to store more information. In summary, our findings support the WGD of C. chinensis shared by Ranunculales, which is likely an allotetraploidization event. This present effort offered new insights into the evolution of key polyploidization events and the genes related to secondary metabolites during the diversification of early eudicots.

Swine Glasser’s disease, instigated by Haemophilus parasuis (H. parasuis), is a significant bacterial infection that causes substantial economic losses in pig farming operations. The role of mucosal immunity is pivotal in defending against H. parasuis. This study focused on the construction of PLGA microspheres that encapsulate the outer membrane protein OMP16 from H. parasuis (PLGA-OMP16) and evaluated their immunological effectiveness in a mouse model. After being intranasally immunized twice, the PLGA-OMP16 microspheres effectively induced IgAs in saliva and nasal and lung fluids. The PLGA-OMP16 microspheres also significantly increased the number of anti H. parasuis IgGs in serum. Furthermore, the PLGA-OMP16 microspheres triggered elevated levels of IL-2, IL-4, and IFN-γ. The mice vaccinated with PLGA-OMP16 showed a significant reduction in H. parasuis burden in the spleen and lungs following bacterial challenge. These results indicate that intranasal immunization using PLGA microspheres is a promising adjuvant delivery system for vaccines targeting H. parasuis.

IntroductionAvian leukosis, a viral disease affecting birds such as chickens, presents significant challenges in poultry farming due to tumor formation, decreased egg production, and increased mortality. Despite the absence of a commercial vaccine, avian leukosis virus (ALV) infections have been extensively documented, resulting in substantial economic losses in the poultry industry. This study aimed to develop alginate-chitosan composite microspheres loaded with ALV-J Gp85 protein (referred to as aCHP-gp85) as a potential vaccine candidate.MethodsSodium alginate and chitosan were utilized as encapsulating materials, with the ALV-J Gp85 protein serving as the active ingredient. The study involved 45 specific pathogen-free (SPF) chickens to evaluate the immunological effectiveness of aCHP-gp85 compared to a traditional Freund adjuvant-gp85 vaccine (Freund-gp85). Two rounds of vaccination were administered, and antibody levels, mRNA expression of immune markers, splenic lymphocyte proliferation, and immune response were assessed. An animal challenge experiment was conducted to evaluate the vaccine’s efficacy in reducing ALV-J virus presence and improving clinical conditions.ResultsThe results demonstrated that aCHP-gp85 induced a significant and sustained increase in antibody levels compared to Freund-gp85, with the elevated response lasting for 84 days. Furthermore, aCHP-gp85 significantly upregulated mRNA expression levels of key immune markers, notably TNF-α and IFN-γ. The application of ALV-J Gp85 protein within the aCHP-gp85 group led to a significant increase in splenic lymphocyte proliferation and immune response. In the animal challenge experiment, aCHP-gp85 effectively reduced ALV-J virus presence and improved clinical conditions compared to other groups, with no significant pathological changes observed.DiscussionThe findings suggest that aCHP-gp85 elicits a strong and prolonged immune response compared to Freund-gp85, indicating its potential as an innovative ALV-J vaccine candidate. These results provide valuable insights for addressing avian leukosis in the poultry industry, both academically and practically.

Abstract Dendritic cells (DCs) serve as a pivotal link connecting innate and adaptive immunity by processing tumor-derived antigens and activating T cells. The advent of single-cell sequencing has revolutionized the categorization of DCs, enabling a high-resolution characterization of the previously unrecognized diversity of DC populations infiltrating the intricate tumor microenvironment (TME). The application of single-cell sequencing technologies has effectively elucidated the heterogeneity of DCs present in the tumor milieu, yielding invaluable insights into their subpopulation structures and functional diversity. This review provides a comprehensive summary of the current state of knowledge regarding DC subtypes in the TME, drawing from single-cell studies conducted across various human tumors. We focused on the categorization, functions, and interactions of distinct DC subsets, emphasizing their crucial roles in orchestrating tumor-related immune responses. Additionally, we delve into the potential implications of these findings for the identification of predictive biomarkers and therapeutic targets. Enhanced insight into the intricate interplay between DCs and the TME promises to advance our comprehension of tumor immunity and, in turn, pave the way for the development of more efficacious cancer immunotherapies.

Chinese mahogany (Toona sinensis) is of considerable medical and economic importance, and its genome has been deciphered. However, the process underlying its polyploidy is unclear, and the chromosomal evolutionary trajectory is poorly understood. Here, by reanalysing the T. sinensis genome, we found evidence of a tetraploidization event (T. sinensis special tetraploidization, TST) that occurred approximately 15–17 million years ago (MYA) after the core eudicot-common hexaploidization (ECH or gamma) event. We characterized the synonymous nucleotide substitution rates (Ks values) of collinear genes and found that T. sinensis genes affected by the TST evolve at a slower rate than Acer yangbiense genes. Furthermore, we identified homologous genes related to polyploidization and speciation and constructed multiple alignments with different reference genomes. Notably, the significant balance of gene retention and loss characterized in the two TST-derived subgenomes suggests an autopolyploid nature of the TST. Moreover, we deduced the chromosomal karyotypes of the two subgenomes and identified 7 chromosomal fusions that have shaped the T. sinensis genome; more information is available on a newly constructed karyotype platform (http://www.cgrpoee.top/Toona_sinensis/index.html). The T. sinensis genome preserves the ancestral chromosome structure of dicotyledons well and could serve as a good reference for understanding genomic changes in other Meliaceae and Sapindales plants. In addition, we verified that tandem duplication and the ECH have promoted the expansion of terpene synthase (TPS) genes; conversely, the TST seems to have inhibited expansion of these genes. This present effort has clarified the polyploidy events of the T. sinensis genome, filled gaps in the history of karyotype evolution, and laid a solid foundation for further genomic studies in the Meliaceae research community and beyond.

Although the portrayal of Zhunti Daoren (Cundī Daoist 準提道人) in the Canonization of the Gods (Fengshen yanyi 封神演義) is relatively subdued, it has garnered considerable scholarly interest owing to the pivotal role he fulfills in advancing the narrative and the profound cultural connotations encapsulated within the character. Scholars have put forward three distinct hypotheses: “Zhunti Daoren as a Buddhist deity”, “Zhunti Daoren as a Daoist deity”, and “Zhunti Daoren as the Panchen Lama”. Based on the theory that the figures in the novels of gods and demons (Shenmo xiaoshuo 神魔小說) embody symbolic characteristics, as well as the sociocultural background of Ming–Qing times, this study uses literary image analysis to investigate these three different interpretations. A basic examination is also performed to explore the correlation between Zhunti Daoren and Jieyin Daoren (Welcoming Daoist接引道人), with the aim of illustrating the relationship between the cult of Zhunti and Pure Land Buddhism in late imperial China.

Abstract Radiochemotherapy (RCT) is a powerful treatment for cervical cancer, which affects not only malignant cells but also the immune and stromal compartments of the tumor. Understanding the remodeling of the local ecosystem induced by RCT would provide valuable insights into improving treatment strategies for cervical cancer. In this study, we applied single-cell RNA-sequencing to paired pre- and post-RCT tumor biopsies from patients with cervical cancer and adjacent normal cervical tissues. We found that the residual population of epithelial cells post-RCT showed upregulated expression of MHC class II genes. Moreover, RCT led to the accumulation of monocytic myeloid-derived suppressor cells with increased pro-inflammatory features and CD16+ NK cells with a higher cytotoxic gene expression signature. However, subclusters of T cells showed no significant increase in the expression of cytotoxic features post-RCT. These results reveal the complex responses of the tumor ecosystem to RCT, providing evidence of activation of innate immunity and MHC-II upregulation in cervical cancer.

Abstract Lithium–sulfur (Li–S) cells have been regarded as attractive alternatives to achieve higher energy densities because of their theoretical specific energy far beyond the lithium-ion cells. However, the achieved results of Li–S cells are exaggerating the cycle performance in their pouch formats because the considerable works are based on the coin cells where flood electrolyte and endless Li supply ensure the Li metal with nature structure features, resulting in a negligible effect on cycle performance caused by the Li dendrites and electrolyte dissipation during cycles. Herein, we demonstrate a strategy to enable the Li metal with lithium fluoride (LiF)-rich solid electrolyte interface via integrating a reinforced interface (RI) embedded with nano-LiF particles on the surface of the Li metal anode. The RI interface enables the solvent molecules of the electrolyte to gain fewer electrons from Li anode, resulting in a lower leakage current of assembled RI||Li–S cell (~ 0 μA) than pristine Li anode (~ 1.15 µA). Moreover, these results show that suppressing lithium dendrite growth is more urgent than inhibiting the shuttle effect of polysulfides in the pouch cell format. As a result, the RI layer-engineered Li metal bears witness to the cyclic stability of Li anode over 800 h, thus achieving stable cycles of Ah-scale Li–S pouch cell with an energy density of 410 Wh/kg at a current of 200 mA per cell. Our study demonstrates that the suppression of lithium dendrites by the RI could be a promising method to prolong the cycle number of Li–S pouch cells.

Abstract As a vital road construction machine, the bridge erecting machine works in a very complex environment. The brake as an important link to maintain the safety and stability of the bridge erecting machine, it will have serious consequences if it is failed. Establishing the brake simulation model and specifying the fault characteristics according to the actual operation status will make it more efficient to find the cause of faults and maintain the safety of machine for a long time. A simulation model of brake of the bridge erecting machine was established by Adams. The brake arms and center axis with obvious data characteristics were flexibly processed, and finite elements were analysed using Abaqus. To verify the accuracy of simulation models, rectangular rosettes were applied to special geometric points, and the strain data were gathered by using the DH3816N collector and compared with the simulation model. The Adams kinematic simulation model was used to simulate the actual operating conditions by the experiment of the disc springs. Two typical fault phenomena were selected: reduced insufficient of disc spring and oil pressure, and two fault characteristics were extracted: variation of the brake shoe clearance and variation of the braking system pressure. When the brake generates the fault characteristics, the normal operation of the brake will not be affected if the fault characteristics are in the first stage. When the fault characteristics are beyond the critical threshold, the faults phenomena of the brake are generated. The results of the simulation experiments proved that the method of using the simulation model to extract the fault characteristics of the braking system and distinguish the causes of the fault was feasible.

The cult of the âGreat Canonâ penetrates many aspects of Chinese culture. However, compared to its great importance, we actually know very little about this cult, especially how ordinary people perceived the âGreat Canonâ in ancient times. To address this topic, the study focuses on the tales (plots) of the âGreat Canonâ in the novels produced in late imperial China. First, I examine the literary discourse on the formation of the âGreat Canonâ in the Ming-Qing (1368â1911) novels. Second, by studying the tales (plots) related to the efficacy of the âGreat Canonâ, I uncover the shared imagination on its function during the Ming-Qing periods. Third, I narrow down the scope of the investigation to Chapter 98 of The Journey to the West and reinterpret the plot of the âwordless scripturesâ.

In this work, the effect of cellulose ether (CE), tartaric acid (TA), and polycarboxylate superplasticizer (PCE) on the working performance and mechanical properties of cement-based self-leveling mortar is investigated. According to the orthogonal experiment analysis, TA is identified as the most influential factor affecting the working performance, as indicated by factors such as fluidity, fluidity loss, and viscosity. Upon conducting a comprehensive assessment of the working performance and mechanical properties, the optimal parameters are found to be CE = 0.6 wt.‰, TA = 0.5 wt.‰, and PCE = 2.0 wt.‰. A univariate test highlights that that the working performance improves with the higher TA dosages. Specifically, the exponential reduction of fluidity loss corresponds with an increased TA content. Regarding the mechanical properties of cement-based self-leveling mortar, the compressive and flexural strength exhibit enhancement when the TA dosage remains below 0.4 wt.‰ at the early stage, implying that TA has some influence on the hydration process. Impressively, the 1 d compressive and flexural strengths surpass 7 MPa and 2 MPa, respectively, ensuring the viability of subsequent construction activities. Through an analysis of hydration heat, the effect mechanism of TA on the cement-based self-leveling mortar is derived. The result shows that the addition of TA decelerates the hydration process within the initial 10 h, followed by acceleration in the subsequent 20 h to 30 h. Consequently, this delayed formation of the early hydration product, ettringite, contributes to a more porous structure in the slurry, with low friction leading to a better working performance. A large number of hydration products, such as alumina gel and calcium–silicon–hydrate gel, presented in the hardened paste results in the good mechanical properties at 1 d. This study may lay a foundation for the optimization of the dosage of chemical admixtures in the self-leveling mortar and high-performance cement-based materials, and also impart valuable insights for practical applications extending to the realm of building construction and decoration.

Lycophytes and seed plants constitute the typical vascular plants. Lycophytes have been thought to have no paleo-polyploidization although the event is known to be critical for the fast expansion of seed plants. Here, genomic analyses including the homologous gene dot plot analysis detected multiple paleo-polyploidization events, with one occurring approximately 13–15 million years ago (MYA) and another about 125–142 MYA, during the evolution of the genome of Selaginella moellendorffii, a model lycophyte. In addition, comparative analysis of reconstructed ancestral genomes of lycophytes and angiosperms suggested that lycophytes were affected by more paleo-polyploidization events than seed plants. Results from the present genomic analyses indicate that paleo-polyploidization has contributed to the successful establishment of both lineages—lycophytes and seed plants—of vascular plants.

Background: Mainstream application of cancer immunotherapy is hampered by the low response rate of most cancer patients. A novel immunotherapeutic target or a biomarker predicting response to immunotherapy needs to be developed. Guanylate-binding protein 1 (GBP1) is an interferon (IFN)-inducible guanosine triphosphatases (GTPases) involving inflammation and infection. However, the immunological effects of GBP1 in pan-cancer patients are still obscure.Methods: Using large-scale public data, we delineated the landscape of GBP1 across 33 cancer types. The correlation between GBP1 expression or mutation and immune cell infiltration was estimated by ESTIMATE, TIMER, xCell, and quanTIseq algorithms. GBP1-related genes and proteins were subjected to function enrichment analysis. Clustering analysis explored the relationship between GBP1 expression and anti-tumor immune phenotypes. We assessed the patient’s response to immunotherapy using the tumor immune dysfunction and exclusion (TIDE) score and immunophenoscore (IPS). Furthermore, we validated the predictive power of GBP1 expression in four independent immunotherapy cohorts.Results: GBP1 was differentially expressed in tumors and normal tissues in multiple cancer types. Distinct correlations existed between GBP1 expression and prognosis in cancer patients. GBP1 expression and mutation were positively associated with immune cell infiltration. Function enrichment analysis showed that GBP1-related genes were enriched in immune-related pathways. Positive correlations were also observed between GBP1 expression and the expression of immune checkpoints, as well as tumor mutation burden (TMB). Pan-cancer patients with higher GBP1 expression were more inclined to display “hot” anti-tumor immune phenotypes and had lower TIDE scores and higher immunophenoscore, suggesting that these patients had better responses to immunotherapy. Patients with higher GBP1 expression exhibited improved overall survival and clinical benefits in immunotherapy cohorts, including the Gide et al. cohort [area under the curve (AUC): 0.813], the IMvigor210 cohort (AUC: 0.607), the Lauss et al. cohort (AUC: 0.740), and the Kim et al. cohort (AUC: 0.793).Conclusion: This study provides comprehensive insights into the role of GBP1 in a pan-cancer manner. We identify GBP1 expression as a predictive biomarker for immunotherapy, potentially enabling more precise and personalized immunotherapeutic strategies in the future.

PurposeFor resectable cases of stage III-N2 non-small cell lung cancer (NSCLC), the best treatment after surgery is still uncertain. The effect of postoperative radiotherapy (PORT) is controversial. Thus, we performed this updated meta-analysis to reassess the data of PORT in stage III-N2 NSCLC patients, to figure out whether these patients can benefit from PORT.MethodsWe conducted searches of the published literature in EMBASE, PubMed, and the Cochrane Library for relevant randomized control trials (RCTs) comparing PORT group with the non-PORT group in NSCLC patients at stage III-N2. These studies allowed the prior chemotherapy in the treatment. We extracted the data from these articles and used the hazard ratios (HRs) and their 95% confidence intervals (CIs) as summary statistics for estimating the effect of PORT on overall survival (OS), disease-free survival (DFS), local-regional recurrence-free survival (LRFS).ResultThe analyses of seven randomized controlled trials (1,318 participants) show no benefit of PORT on survival (HR, 0.87; 95% CI, 0.71 to 1.07; p = 0.18) but a significantly different effect of PORT on DFS (HR, 0.83; 95% CI, 0.71 to 0.97; p = 0.02) and LRFS (HR, 0.64; 95% CI, 0.50 to 0.81; p = 0.0003). There is not enough evidence of a difference in the effect on survival by the utility of chemotherapy along with PORT though subgroup analysis of no chemotherapy group, concurrent chemoradiotherapy and sequential chemoradiotherapy group. Even in trials with 3D-CRT radiation technique, the pooled analysis shows no benefit of PORT on survival in patients with stage III-N2 NSCLC (data is not shown).ConclusionOur findings illustrate that in the postoperative treatment for patients with stage III-N2 NSCLC, PORT contributes to a significantly increased DFS and LR and may not associate with an improved OS, indicating a cautious selection.

Immunotherapy has moved to the forefront of modern oncologic treatment in the past few decades. Various forms of immunotherapy currently are emerging, including oncolytic viruses. In this therapy, viruses are engineered to selectively propagate in tumor cells and reduce toxicity for non-neoplastic tissues. Adenovirus is one of the most frequently employed oncolytic viruses because of its capacity in tumor cell lysis and immune response stimulation. Upregulation of immunostimulatory signals induced by oncolytic adenoviruses (OAds) might significantly remove local immune suppression and amplify antitumor immune responses. Existing genetic engineering technology allows us to design OAds with increasingly better tumor tropism, selectivity, and antitumor efficacy. Several promising strategies to modify the genome of OAds have been applied: capsid modifications, small deletions in the pivotal viral genes, insertion of tumor-specific promoters, and addition of immunostimulatory transgenes. OAds armed with tumor-associated antigen (TAA) transgenes as cancer vaccines provide additional therapeutic strategies to trigger tumor-specific immunity. Furthermore, the combination of OAds and immune checkpoint inhibitors (ICIs) increases clinical benefit as evidence shown in completed and ongoing clinical trials, especially in the combination of OAds with antiprogrammed death 1/programed death ligand 1 (PD-1/PD-L1) therapy. Despite remarkable antitumor potency, oncolytic adenovirus immunotherapy is confronted with tough challenges such as antiviral immune response and obstruction of tumor microenvironment (TME). In this review, we focus on genomic modification strategies of oncolytic adenoviruses and applications of OAds in cancer immunotherapy.

The address one of the major challenges facing the lithium metal anode, here the authors use lithiophilic montmorillonite as an additive to the ether-based electrolyte to regulate the lithium ion concentration on the anode surface, facilitating uniform lithium deposition.

Abstract Background After polyploidization, a genome may experience large-scale genome-repatterning, featuring wide-spread DNA rearrangement and loss, and often chromosome number reduction. Grasses share a common tetraploidization, after which the originally doubled chromosome numbers reduced to different chromosome numbers among them. A telomere-centric reduction model was proposed previously to explain chromosome number reduction. With Brachpodium as an intermediate linking different major lineages of grasses and a model plant of the Pooideae plants, we wonder whether it mediated the evolution from ancestral grass karyotype to Triticeae karyotype. Results By inferring the homology among Triticeae, rice, and Brachpodium chromosomes, we reconstructed the evolutionary trajectories of the Triticeae chromosomes. By performing comparative genomics analysis with rice as a reference, we reconstructed the evolutionary trajectories of Pooideae plants, including Ae. Tauschii (2n = 14, DD), barley (2n = 14), Triticum turgidum (2n = 4x = 28, AABB), and Brachypodium (2n = 10). Their extant Pooidea and Brachypodium chromosomes were independently produced after sequential nested chromosome fusions in the last tens of millions of years, respectively, after their split from rice. More frequently than would be expected by chance, in Brachypodium, the ‘invading’ and ‘invaded’ chromosomes are homoeologs, originating from duplication of a common ancestral chromosome, that is, with more extensive DNA-level correspondence to one another than random chromosomes, nested chromosome fusion events between homoeologs account for three of seven cases in Brachypodium (P-value≈0.00078). However, this phenomenon was not observed during the formation of other Pooideae chromosomes. Conclusions Notably, we found that the Brachypodium chromosomes formed through exclusively distinctive trajectories from those of Pooideae plants, and were well explained by the telomere-centric model. Our work will contribute to understanding the structural and functional innovation of chromosomes in different Pooideae lineages and beyond.

NAC transcription factors play an important regulatory role in tomato fruit ripening. We chose a novel perspective to explore the traces left by two paleopolyploidizations in the NAC family using a bioinformatics approach. We found that 85 (S. lycopersicum) and 88 (S. pennellii) members of the NAC family were present in two tomatoes, and most of them were amplified from two paleohexaploidizations. We differentiated NAC family members from the different paleohexaploidizations and found that the SWGT-derived NAC genes had more rearrangement events, so it was different from the DWGT-derived NAC genes in terms of physicochemical properties, phylogeny, and gene location. The results of selection pressure show that DWGT-derived NAC genes tended to be positively selected in S. lycopersicum and negatively selected in S. pennellii. A comprehensive analysis of paleopolyploidization and expression reveals that DWGT-derived NAC genes tend to promote fruit ripening, and are expressed at the early and middle stages, whereas SWGT-derived NAC genes tend to terminate fruit growth and are expressed at the late stages of fruit ripening. This study obtained NAC genes from different sources that can be used as materials for tomato fruit development, and the method in the study can be extended to the study of other plants.

The alkaline components in red mud represent one of the crucial factors restricting its application, especially for the construction and building industry. The phase state of alkaline components has a significant influence on the dealkalization of red mud. In this work, an environmentally friendly acid leaching strategy is proposed by controlling the phase transformation of red mud during active roasting pretreatment. With a moderate roasting temperature, the alkaline component is prevented from converting into insoluble phases. After acid leaching with a low concentration of 0.1 M, a high dealkalization rate of 92.8% is obtained. Besides, the leachate is neutral (pH = 7) and the valuable metals in red mud are well preserved, manifesting a high selectivity and efficiency of diluted acid leaching. The calcination experiment further confirms the practicability of the strategy in the construction field, where the cementitious minerals can be formed in large quantities. Compared with the traditional acid leaching routes, the diluted acid leaching strategy in this work is acid saving with low valuable element consumption. Meanwhile, the secondary pollution issue can be alleviated. Hence, the findings in this work provide a feasible approach for the separation and recovery of alkali and resource utilization of red mud.

Abstract Background Trihelix transcription factors (TTF) play important roles in plant growth and response to adversity stress. Until now, genome-wide identification and analysis of this gene family in foxtail millet has not been available. Here, we identified TTF genes in the foxtail millet and its grass relatives, and characterized their functional domains. Results As to sequence divergence, TTF genes were previously divided into five subfamilies, I-V. We found that Trihelix family members in foxtail millet and other grasses mostly preserved their ancestral chromosomal locations during millions of years’ evolution. Six amino acid sites of the SIP1 subfamily possibly were likely subjected to significant positive selection. Highest expression level was observed in the spica, with the SIP1 subfamily having highest expression level. As to the origination and expansion of the gene family, notably we showed that a subgroup of subfamily IV was the oldest, and therefore was separated to define a new subfamily O. Overtime, starting from the subfamily O, certain genes evolved to form subfamilies III and I, and later from subfamily I to develop subfamilies II and V. The oldest gene, Si1g016284, has the most structural changes, and a high expression in different tissues. What’s more interesting is that it may have bridge the interaction with different proteins. Conclusions By performing phylogenetic analysis using non-plant species, notably we showed that a subgroup of subfamily IV was the oldest, and therefore was separated to define a new subfamily O. Starting from the subfamily O, certain genes evolved to form other subfamilies. Our work will contribute to understanding the structural and functional innovation of Trihelix transcription factor, and the evolutionary trajectory.

Polyploidy has contributed to the divergence and domestication of plants; however, estimation of the relative roles that different types of polyploidy have played during evolution has been difficult. Unbalanced and balanced gene removal was previously related to allopolyploidies and autopolyploidies, respectively. Here, to infer the types of polyploidies and evaluate their evolutionary effects, we devised a statistic, the Polyploidy-index or P-index, to characterize the degree of divergence between subgenomes of a polyploidy, to find whether there has been a balanced or unbalanced gene removal from the homoeologous regions. Based on a P-index threshold of 0.3 that distinguishes between known or previously inferred allo- or autopolyploidies, we found that 87.5% of 24 angiosperm paleo-polyploidies were likely produced by allopolyploidizations, responsible for establishment of major tribes such as Poaceae and Fabaceae, and large groups such as monocots and eudicots. These findings suggest that >99.7% of plant genomes likely derived directly from allopolyploidies, with autopolyploidies responsible for the establishment of only a few small genera, including Glycine, Malus, and Populus, each containing tens of species. Overall, these findings show that polyploids with high divergence between subgenomes (presumably allopolyploids) established the major plant groups, possibly through secondary contact between previously isolated populations and hybrid vigor associated with their re-joining.

This study traces the trajectory of the Wenshu Monastery’s revival during the reform era of China. In this special but duplicable case, we generalize three key strategies employed by the Wenshu Monastery to enhance its reputation and status—the binomial system, centralized organizational structure, and officialization—in an attempt to rethink the patterns of development of local religious institutions in modern China.

Rice is one of the most researched model plant, and has a genome structure most resembling that of the grass common ancestor after a grass common tetraploidization ~100 million years ago. There has been a standing controversy whether there had been 5 or 7 basic chromosomes, before the tetraploidization, which were tackled but could not be well solved for the lacking of a sequenced and assembled outgroup plant to have a conservative genome structure. Recently, the availability of pineapple genome, which has not been subjected to the grass-common tetraploidization, provides a precious opportunity to solve the above controversy and to research into genome changes of rice and other grasses. Here, we performed a comparative genomics analysis of pineapple and rice, and found solid evidence that grass-common ancestor had 2n =2x =14 basic chromosomes before the tetraploidization and duplicated to 2n = 4x = 28 after the event. Moreover, we proposed that enormous gene missing from duplicated regions in rice should be explained by an allotetraploid produced by prominently divergent parental lines, rather than gene losses after their divergence. This means that genome fractionation might have occurred before the formation of the allotetraploid grass ancestor.

The AP2/ERF superfamily, one of the most important transcription factor families, plays crucial roles in response to biotic and abiotic stresses. So far, a comprehensive evolutionary inference of its origination and expansion has not been available. Here, we identified 515 AP2/ERF genes in B. napus, a neo-tetraploid forming ~7500 years ago, and found that 82.14% of them were duplicated in the tetraploidization. A prominent subgenome bias was revealed in gene expression, tissue-specific, and gene conversion. Moreover, a large-scale analysis across plants and alga suggested that this superfamily could have been originated from AP2 family, expanding to form other families (ERF, and RAV). This process was accompanied by duplicating and/or alternative deleting AP2 domain, intragenic domain sequence conversion, and/or by acquiring other domains, resulting in copy number variations, alternatively contributing to functional innovation. We found that significant positive selection occurred at certain critical nodes during the evolution of land plants, possibly responding to changing environment. In conclusion, the present research revealed origination, functional innovation, and evolutionary trajectory of the AP2/ERF superfamily, contributing to understanding their roles in plant stress tolerance.