Single-cell landscape of immunological responses in patients with COVID-19.

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.

pathMap: a path-based mapping tool for long noisy reads with high sensitivity.

With the rapid development of single-molecule sequencing (SMS) technologies, the output read length is continuously increasing. Mapping such reads onto a reference genome is one of the most fundamental tasks in sequence analysis. Mapping sensitivity is becoming a major concern since high sensitivity can detect more aligned regions on the reference and obtain more aligned bases, which are useful for downstream analysis. In this study, we present pathMap, a novel k-mer graph-based mapper that is specifically designed for mapping SMS reads with high sensitivity. By viewing the alignment chain as a path containing as many anchors as possible in the matched k-mer graph, pathMap treats chaining as a path selection problem in the directed graph. pathMap iteratively searches the longest path in the remaining nodes; more candidate chains with high quality can be effectively detected and aligned. Compared to other state-of-the-art mapping methods such as minimap2 and Winnowmap2, experiment results on simulated and real-life datasets demonstrate that pathMap obtains the number of mapped chains at least 11.50% more than its closest competitor and increases the mapping sensitivity by 17.28% and 13.84% of bases over the next-best mapper for Pacific Biosciences and Oxford Nanopore sequencing data, respectively. In addition, pathMap is more robust to sequence errors and more sensitive to species- and strain-specific identification of pathogens using MinION reads.

Overexpression of plant chitin receptors in wheat confers broad-spectrum resistance to fungal diseases.

Wheat (Triticum aestivum L.) is a globally staple crop vulnerable to various fungal diseases, significantly impacting its yield. Plant cell surface receptors play a crucial role in recognizing pathogen-associated molecular patterns (PAMPs) and activating PAMP-triggered immunity, boosting resistance against a wide range of plant diseases. Although the role of plant chitin receptor CERK1 in immune recognition and defense has been established in Arabidopsis and rice, its function and potential agricultural applications in enhancing resistance to crop diseases remain largely unexplored. Here, we identify and characterize TaCERK1 in Triticeae crop wheat, uncovering its involvement in chitin recognition, immune regulation, and resistance to fungal diseases. By a comparative analysis of CERK1 homologs in Arabidopsis and monocot crops, we demonstrate that AtCERK1 in Arabidopsis elicits the most robust immune response. Moreover, we show that overexpressing TaCERK1 and AtCERK1 in wheat confers resistance to multiple fungal diseases, including Fusarium head blight, stripe rust, and powdery mildew. Notably, transgenic wheat lines with moderately expressed AtCERK1 display superior disease resistance and heightened immune responses without adversely affecting growth and yield, compared to TaCERK1 overexpression transgenics. Our findings highlight the significance of plant chitin receptors across diverse plant species and suggest potential strategies for bolstering crop resistance against broad-spectrum diseases in agricultural production through the utilization of plant immune receptors.

Genetic factors of grain cadmium concentration in Polish wheat (Triticum polonicum L.).

Wheat (Triticum aestivum L.) is one of the most important crops worldwide and a major source of human cadmium (Cd) intake. Limiting grain Cd concentration (Gr_Cd_Conc) in wheat is necessary to ensure food safety. However, the genetic factors associated with Cd uptake, translocation and distribution and Gr_Cd_Conc in wheat are poorly understood. Here, we mapped quantitative trait loci (QTLs) for Gr_Cd_Conc and its related transport pathway using a recombinant inbred line (RIL) population derived from 2 Polish wheat varieties (RIL_DT; dwarf Polish wheat [DPW] and tall Polish wheat [TPW]). We identified 29 novel major QTLs for grain and tissue Cd concentration; 14 novel major QTLs for Cd uptake, translocation, and distribution; and 27 major QTLs for agronomic traits. We also analyzed the pleiotropy of these QTLs. Six novel QTLs (QGr_Cd_Conc-1A, QGr_Cd_Conc-3A, QGr_Cd_Conc-4B, QGr_Cd_Conc-5B, QGr_Cd_Conc-6A, and QGr_Cd_Conc-7A) for Gr_Cd_Conc explained 8.16% to 17.02% of the phenotypic variation. QGr_Cd_Conc-3A, QGr_Cd_Conc-6A, and QGr_Cd_Conc-7A pleiotropically regulated Cd transport; 3 other QTLs were organ-specific for Gr_Cd_Conc. We fine-mapped the locus of QGr_Cd_Conc-4B and identified the candidate gene as Cation/Ca exchanger 2 (TpCCX2-4B), which was differentially expressed in DPW and TPW. It encodes an endoplasmic reticulum membrane/plasma membrane-localized Cd efflux transporter in yeast. Overexpression of TpCCX2-4B reduced Gr_Cd_Conc in rice. The average Gr_Cd_Conc was significantly lower in TpCCX2-4BDPW genotypes than in TpCCX2-4BTPW genotypes of the RIL_DT population and 2 other natural populations, based on a Kompetitive allele-specific PCR marker derived from the different promoter sequences between TpCCX2-4BDPW and TpCCX2-4BTPW. Our study reveals the genetic mechanism of Cd accumulation in wheat and provides valuable resources for genetic improvement of low-Cd-accumulating wheat cultivars.

Chromosome-specific painting reveals the Y genome origin and chromosome rearrangements of the St genome in Triticeae.

Karyotypes provide key cytogenetic information on phylogenetic relationships and evolutionary origins in related plant species. The St genome of Pseudoroegneria contributes to 8 alloploid genera, representing over half of the species that are highly valuable for wheat (Triticum aestivum) breeding and for understanding Triticeae species evolution. However, St chromosome characterization is challenging due to limited cytogenetic markers and DNA information. We developed a complete set of St genome-specific chromosome painting probes for identification of the individual chromosomes 1St to 7St based on the genome sequences of Pseudoroegneria libanotica and wheat. We revealed the conservation of St chromosomes in St-containing species by chromosome painting, including Pseudoroegneria, Roegneria, Elymus, and Campeiostachys. Notably, the Y genome showed hybridization signals, albeit weaker than those of the St genome. The awnless species harboring the Y genome exhibited more intense hybridization signals compare to the awned species in Roegneria and Campeiostachys, yet weaker than the hybridization signals of the St genome in autotetraploid Pseudoroegneria strigosa. Although awnless species were morphologically more similar to each other, phenotypic divergence progressively increased from awnless to awned species. Our results indicate that the Y genome originated from the St genome and shed light on the possible origin of the Roegneria and Campeiostachys species, enhancing our understanding of St-genome-containing species evolution.

Differential diagnosis of bone marrow failure syndromes guided by machine learning.

The choice to postpone treatment while awaiting genetic testing can result in significant delay in definitive therapies in patients with severe pancytopenia. Conversely, the misdiagnosis of inherited bone marrow failure (BMF) can expose patients to ineffectual and expensive therapies, toxic transplant conditioning regimens, and inappropriate use of an affected family member as a stem cell donor. To predict the likelihood of patients having acquired or inherited BMF, we developed a 2-step data-driven machine-learning model using 25 clinical and laboratory variables typically recorded at the initial clinical encounter. For model development, patients were labeled as having acquired or inherited BMF depending on their genomic data. Data sets were unbiasedly clustered, and an ensemble model was trained with cases from the largest cluster of a training cohort (n = 359) and validated with an independent cohort (n = 127). Cluster A, the largest group, was mostly immune or inherited aplastic anemia, whereas cluster B comprised underrepresented BMF phenotypes and was not included in the next step of data modeling because of a small sample size. The ensemble cluster A-specific model was accurate (89%) to predict BMF etiology, correctly predicting inherited and likely immune BMF in 79% and 92% of cases, respectively. Our model represents a practical guide for BMF diagnosis and highlights the importance of clinical and laboratory variables in the initial evaluation, particularly telomere length. Our tool can be potentially used by general hematologists and health care providers not specialized in BMF, and in under-resourced centers, to prioritize patients for genetic testing or for expeditious treatment.

Mapping of Long-Wavelength Phonon Contribution in the Thermal Transport of Alloyed Semiconductor Superlattices.

The mapping of long-wavelength phonons is important to understand and manipulate the thermal transport in multilayered structures, but it remains a long-standing challenge due to the collective behaviors of phonons. In this study, an experimental demonstration of mapping the long-wavelength phonons in an alloyed Al0.1Ga0.9As/Al0.9Ga0.1As superlattice system is reported. Multiple strategies to filter out the short- to mid-wavelength phonons are used. The phonon mean-free-path-dependent thermal transport properties directly demonstrate both the suppression effect of the ErAs nanoislands and the contribution of long-wavelength phonons. The contribution from phonons with mean free path longer than 1 µm is clearly demonstrated. A model based on the Boltzmann transport equation is proposed to calculate and describe the thermal transport properties, which depicts a clear physical picture of the transport mechanisms. This method can be extended to map different wavelength phonons and become a universal strategy to explore their thermal transport in various application scenarios.

Holistic immunomodulation for small cell lung cancer.

Small cell lung cancer (SCLC) is characterized by a high mortality rate, rapid growth, and early metastasis, which lead to a poor prognosis. Moreover, limited clinical treatment options further lower the survival rate of patients. Therefore, novel technology and agents are urgently required to enhance clinical efficacy. In this review, from a holistic perspective, we summarized the therapeutic targets, agents and strategies with the most potential for treating SCLC, including chimeric antigen receptor (CAR) T therapy, immunomodulating antibodies, traditional Chinese medicines (TCMs), and the microbiota, which have been found recently to improve the clinical outcomes and prognosis of SCLC. Multiomics technologies can be integrated to develop effective diagnostic methods and identify new targets for new drug discovery in SCLC. We discussed in depth the feasibility, potential, and challenges of these new strategies, as well as their combinational treatments, which may provide promising alternatives for enhancing the clinical efficacy of SCLC in the future.

NPS-2143 inhibit glioma progression by suppressing autophagy through mediating AKT-mTOR pathway.

Gliomas are the most common tumours in the central nervous system. In the present study, we aimed to find a promising anti-glioma compound and investigate the underlying molecular mechanism. Glioma cells were subjected to the 50 candidate compounds at a final concentration of 10 µM for 72 h, and CCK-8 was used to evaluate their cytotoxicity. NPS-2143, an antagonist of calcium-sensing receptor (CASR), was selected for further study due to its potent cytotoxicity to glioma cells. Our results showed that NPS-2143 could inhibit the proliferation of glioma cells and induce G1 phase cell cycle arrest. Meanwhile, NPS-2143 could induce glioma cell apoptosis by increasing the caspase-3/6/9 activity. NPS-2143 impaired the immigration and invasion ability of glioma cells by regulating the epithelial-mesenchymal transition process. Mechanically, NPS-2143 could inhibit autophagy by mediating the AKT-mTOR pathway. Bioinformatic analysis showed that the prognosis of glioma patients with low expression of CASR mRNA was better than those with high expression of CASR mRNA. Gene set enrichment analysis showed that CASR was associated with cell adhesion molecules and lysosomes in glioma. The nude mice xenograft model showed NPS-2143 could suppress glioma growth in vivo. In conclusion, NPS-2143 can suppress the glioma progression by inhibiting autophagy.

A chromosome level genome assembly of Pseudoroegneria Libanotica reveals a key Kcs gene involves in the cuticular wax elongation for drought resistance.

BACKGROUND: The genus Pseudoroegneria (Nevski) Löve (Triticeae, Poaceae), whose genome symbol was designed as "St", accounts for more than 60% of perennial Triticeae species. The diploid species Psudoroegneria libanotica (2n = 14) contains the most ancient St genome, exhibited strong drought resistance, and was morphologically covered by cuticular wax on the aerial part. Therefore, the St-genome sequencing data could provide fundamental information for studies of genome evolution and reveal its mechanisms of cuticular wax and drought resistance. RESULTS: In this study, we reported the chromosome-level genome assembly for the St genome of Pse. libanotica, with a total size of 2.99 Gb. 46,369 protein-coding genes annotated and 71.62% was repeat sequences. Comparative analyses revealed that the genus Pseudoroegneria diverged during the middle and late Miocene. During this period, unique genes, gene family expansion, and contraction in Pse. libanotica were enriched in biotic and abiotic stresses, such as fatty acid biosynthesis which may greatly contribute to its drought adaption. Furthermore, we investigated genes associated with the cuticular wax formation and water deficit and found a new Kcs gene evm.TU.CTG175.54. It plays a critical role in the very long chain fatty acid (VLCFA) elongation from C18 to C26 in Pse. libanotica. The function needs more evidence to be verified. CONCLUSIONS: We sequenced and assembled the St genome in Triticeae and discovered a new KCS gene that plays a role in wax extension to cope with drought. Our study lays a foundation for the genome diversification of Triticeae species and deciphers cuticular wax formation genes involved in drought resistance.

Soil application of FeCl3 and Fe2(SO4)3 reduced grain cadmium concentration in Polish wheat (Triticum polonicum L.).

BACKGROUND: Wheat is one of major sources of human cadmium (Cd) intake. Reducing the grain Cd concentrations in wheat is urgently required to ensure food security and human health. In this study, we performed a field experiment at Wenjiang experimental field of Sichuan Agricultural University (Chengdu, China) to reveal the effects of FeCl3 and Fe2(SO4)3 on reducing grain Cd concentrations in dwarf Polish wheat (Triticum polonicum L., 2n = 4x = 28, AABB). RESULTS: Soil application of FeCl3 and Fe2(SO4)3 (0.04 M Fe3+/m2) significantly reduced grain Cd concentration in DPW at maturity by 19.04% and 33.33%, respectively. They did not reduce Cd uptake or root-to-shoot Cd translocation, but increased Cd distribution in lower leaves, lower internodes, and glumes. Meanwhile, application of FeCl3 and Fe2(SO4)3 up-regulated the expression of TpNRAMP5, TpNRAMP2 and TpYSL15 in roots, and TpYSL15 and TpZIP3 in shoots; they also downregulated the expression of TpZIP1 and TpZIP3 in roots, and TpIRT1 and TpNRAMP5 in shoots. CONCLUSIONS: The reduction in grain Cd concentration caused by application of FeCl3 and Fe2(SO4)3 was resulted from changes in shoot Cd distribution via regulating the expression of some metal transporter genes. Overall, this study reports the physiological pathways of soil applied Fe fertilizer on grain Cd concentration in wheat, suggests a strategy for reducing grain Cd concentration by altering shoot Cd distribution.

Characterization of the wheat-tetraploid Thinopyrum elongatum 7E(7D) substitution line with Fusarium head blight resistance.

BACKGROUND: Fusarium head blight (FHB), a devastating disease of wheat production, is predominantly elicited by Fusarium graminearum (Fg). The tetraploid Thinopyrum elongatum is a tertiary gene resource of common wheat that possesses high affinity and displays high resistance traits against multiple biotic and abiotic stress. We aim to employ and utilize the novel FHB resistance resources from the wild germplasm of common wheat for breeding. RESULTS: Durum wheat-tetraploid Th. elongatum amphiploid 8801 was hybridized with common wheat cultivars SM482 and SM51, and the F5 generation was generated. We conducted cytogenetically in situ hybridization (ISH) technologies to select and confirm a genetically stable 7E(7D) substitution line K17-1069-5, which showed FHB expansion resistance in both field and greenhouse infection experiments and displayed no significant disadvantage in agronomic traits compared to their common wheat parents in the field. The F2 segregation populations (K17-1069-5 × SM830) showed that the 7E chromosome conferred dominant FHB resistance with dosage effect. We developed 19 SSR molecular markers specific to chromosome 7E, which could be conducted for genetic mapping and large breeding populations marker-assisted selection (MAS) during selection procedures in the future. We isolated a novel Fhb7 allele from the tetraploid Th. elongatum chromosome 7E (Chr7E) using homology-based cloning, which was designated as TTE7E-Fhb7. CONCLUSIONS: In summary, our study developed a novel wheat-tetraploid Thinopyrum elongatum 7E(7D) K17-1069-5 substitution line which contains stable FHB resistance.

Copper Single-Atom Catalysts-A Rising Star for Energy Conversion and Environmental Purification: Synthesis, Modification, and Advanced Applications.

Future renewable energy supply and green, sustainable environmental development rely on various types of catalytic reactions. Copper single-atom catalysts (Cu SACs) are attractive due to their distinctive electronic structure (3d orbitals are not filled with valence electrons), high atomic utilization, and excellent catalytic performance and selectivity. Despite numerous optimization studies are conducted on Cu SACs in terms of energy conversion and environmental purification, the coupling among Cu atoms-support interactions, active sites, and catalytic performance remains unclear, and a systematic review of Cu SACs is lacking. To this end, this work summarizes the recent advances of Cu SACs. The synthesis strategies of Cu SACs, metal-support interactions between Cu single atoms and different supports, modification methods including modification for carriers, coordination environment regulating, site distance effect utilizing, and dual metal active center catalysts constructing, as well as their applications in energy conversion and environmental purification are emphatically introduced. Finally, the opportunities and challenges for the future Cu SACs development are discussed. This review aims to provide insight into Cu SACs and a reference for their optimal design and wide application.

Abscisic acid-induced H2O2 production positively regulates the activity of SAPK8/9/10 through oxidation of the type one protein phosphatase OsPP47.

Subclass III sucrose nonfermenting1-related protein kinase 2s (SnRK2s) are positive regulators of abscisic acid (ABA) signaling and abiotic stress responses. However, the underlying activation mechanisms of osmotic stress/ABA-activated protein kinase 8/9/10 (SAPK8/9/10) of rice (Oryza sativa) subclass III SnRK2s in ABA signaling remain to be elucidated. In this study, we employed biochemical, molecular biology, cell biology, and genetic approaches to identify the molecular mechanism by which OsPP47, a type one protein phosphatase in rice, regulates SAPK8/9/10 activity in ABA signaling. We found that OsPP47 not only physically interacted with SAPK8/9/10 but also interacted with ABA receptors PYLs. OsPP47 negatively regulated ABA sensitivity in seed germination and root growth. In the absence of ABA, OsPP47 directly inactivated SAPK8/9/10 by dephosphorylation. In the presence of ABA, ABA-bound OsPYL2 formed complexes with OsPP47 and inhibited its phosphatase activity, partially releasing the inhibition of SAPK8/9/10. SAPK8/9/10-mediated H2O2 production inhibited OsPP47 activity by oxidizing Cys-116 and Cys-256 to form OsPP47 oligomers, resulting in not only preventing the OsPP47-SAPK8/9/10 interaction but also blocking the inhibition of SAPK8/9/10 activity by OsPP47. Our results reveal novel pathways for the inhibition of SAPK8/9/10 in the basal state and for the activation of SAPK8/9/10 induced by ABA in rice.

Studies of a mosaic patient with DBA and chimeric mice reveal erythroid cell-extrinsic contributions to erythropoiesis.

We follow a patient with Diamond-Blackfan anemia (DBA) mosaic for a pathogenic RPS19 haploinsufficiency mutation with persistent transfusion-dependent anemia. Her anemia remitted on eltrombopag (EPAG), but surprisingly, mosaicism was unchanged, suggesting that both mutant and normal cells responded. When EPAG was withheld, her anemia returned. In addition to expanding hematopoietic stem/progenitor cells, EPAG aggressively chelates iron. Because DBA anemia, at least in part, results from excessive intracellular heme leading to ferroptotic cell death, we hypothesized that the excess heme accumulating in ribosomal protein-deficient erythroid precursors inhibited the growth of adjacent genetically normal precursors, and that the efficacy of EPAG reflected its ability to chelate iron, limit heme synthesis, and thus limit toxicity in both mutant and normal cells. To test this, we studied Rpl11 haploinsufficient (DBA) mice and mice chimeric for the cytoplasmic heme export protein, FLVCR. Flvcr1-deleted mice have severe anemia, resembling DBA. Mice transplanted with ratios of DBA to wild-type marrow cells of 50:50 are anemic, like our DBA patient. In contrast, mice transplanted with Flvcr1-deleted (unable to export heme) and wild-type marrow cells at ratios of 50:50 or 80:20 have normal numbers of red cells. Additional studies suggest that heme exported from DBA erythroid cells might impede the nurse cell function of central macrophages of erythroblastic islands to impair the maturation of genetically normal coadherent erythroid cells. These findings have implications for the gene therapy of DBA and may provide insights into why del(5q) myelodysplastic syndrome patients are anemic despite being mosaic for chromosome 5q deletion and loss of RPS14.

A macaque clonal hematopoiesis model demonstrates expansion of TET2-disrupted clones and utility for testing interventions.

Individuals with age-related clonal hematopoiesis (CH) are at greater risk for hematologic malignancies and cardiovascular diseases. However, predictive preclinical animal models to recapitulate the spectrum of human CH are lacking. Through error-corrected sequencing of 56 human CH/myeloid malignancy genes, we identified natural CH driver mutations in aged rhesus macaques matching genes somatically mutated in human CH, with DNMT3A mutations being the most frequent. A CH model in young adult macaques was generated via autologous transplantation of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated gene-edited hematopoietic stem and progenitor cells (HSPCs), targeting the top human CH genes with loss-of-function (LOF) mutations. Long-term follow-up revealed reproducible and significant expansion of multiple HSPC clones with heterozygous TET2 LOF mutations, compared with minimal expansion of clones bearing other mutations. Although the blood counts of these CH macaques were normal, their bone marrows were hypercellular and myeloid-predominant. TET2-disrupted myeloid colony-forming units isolated from these animals showed a distinct hyperinflammatory gene expression profile compared with wild type. In addition, mature macrophages purified from the CH macaques showed elevated NLRP3 inflammasome activity and increased interleukin-1ß (IL-1ß) and IL-6 production. The model was used to test the impact of IL-6 blockage by tocilizumab, documenting a slowing of TET2-mutated expansion, suggesting that interruption of the IL-6 axis may remove the selective advantage of mutant HSPCs. These findings provide a model for examining the pathophysiology of CH and give insights into potential therapeutic interventions.

Development of wheat-tetraploid Thinopyrum elongatum 4EL small fragment translocation lines with stripe rust resistance gene Yr4EL.

KEY MESSAGE: Two small fragment translocation lines (T4DS·4DL-4EL and T5AS·5AL-4EL) showed high resistance to stripe rust and resistance gene Yr4EL was localized to an about 35 Mb region at the end of chr arm 4EL. Stripe rust, caused by the fungus Puccinia striiformis f. sp. tritici, is a devastating wheat disease worldwide. Deployment of disease resistance (R) genes in wheat cultivars is the most effective way to control the disease. Previously, the all-stage stripe rust R gene Yr4EL from tetraploid Thinopyrum elongatum was introduced into common wheat as 4E(4D) substitution and T4DS·4EL translocation lines. To further map and utilize Yr4EL, Chinese Spring (CS) mutant pairing homoeologous gene ph1b was used in crossing to induce recombination between chromosome (chr) 4EL and wheat chromosomes. Two small fragment translocation lines T4DS·4DL-4EL and T5AS·5AL-4EL with Yr4EL resistance were selected using molecular markers and confirmed by genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH), and Wheat 660 K SNP array analyses. We mapped Yr4EL to an about 35 Mb region at the end of chr 4EL, corresponding to 577.76-612.97 Mb based on the diploid Th. elongatum reference genome. In addition, two competitive allele-specific PCR (KASP) markers co-segregating with Yr4EL were developed to facilitate molecular marker-assisted selection in breeding. The T4DS·4DL-4EL lines were crossed and backcrossed with wheat cultivars SM482 and CM42, and the resulting pre-breeding lines showed high stripe rust resistance and potential for wheat breeding with good agronomic traits. These lines represent new germplasm for wheat stripe rust resistance breeding, as well as providing a solid foundation for Yr4EL fine mapping and cloning.

Development, identification, and utilization of wheat-tetraploid Thinopyrum elongatum 4EL translocation lines resistant to stripe rust.

KEY MESSAGE: The new stripe rust resistance gene Yr4EL in tetraploid Th. elongatum was identified and transferred into common wheat via 4EL translocation lines. Tetraploid Thinopyrum elongatum is a valuable genetic resource for improving the resistance of wheat to diseases such as stripe rust, powdery mildew, and Fusarium head blight. We previously reported that chromosome 4E of the 4E (4D) substitution line carries all-stage stripe rust resistance genes. To optimize the utility of these genes in wheat breeding programs, we developed translocation lines by inducing chromosomal structural changes through 60Co-γ irradiation and developing monosomic substitution lines. In total, 53 plants with different 4E chromosomal structural changes were identified. Three homozygous translocation lines (T4DS·4EL, T5AL·4EL, and T3BL·4EL) and an addition translocation line (T5DS·4EL) were confirmed by the genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH), FISH-painting, and wheat 55 K SNP array analyses. These four translocation lines, which contained chromosome arm 4EL, exhibited high stripe rust resistance. Thus, a resistance gene (tentatively named Yr4EL) was localized to the chromosome arm 4EL of tetraploid Th. elongatum. For the application of marker-assisted selection (MAS), 32 simple sequence repeat (SSR) markers were developed, showing specific amplification on the chromosome arm 4EL and co-segregation with Yr4EL. Furthermore, the 4DS·4EL line could be selected as a good pre-breeding line that better agronomic traits than other translocation lines. We transferred Yr4EL into three wheat cultivars SM482, CM42, and SM51, and their progenies were all resistant to stripe rust, which can be used in future wheat resistance breeding programs.

Depletion of regulatory T cells enhancing the anti-tumor effect of in situ vaccination in solid tumors.

The emergence of immune checkpoint inhibitors (ICIs) has revolutionized the clinical treatment for tumor. However, the low response rate of ICIs remains the major obstacle for curing patients and effective approaches for patients with primary or secondary resistance to ICIs remain lacking. In this study, immune stimulating agent unmethylated CG-enriched (CpG) oligodeoxynucleotide (ODN) was locally injected into the tumor to trigger a robust immune response to eradicate cancer cells, while anti-CD25 antibody was applied to remove immunosuppressive regulatory T cells, which further enhanced the host immune activity to attack tumor systematically. The combination of CpG and anti-CD25 antibody obtained notable regression in mouse melanoma model. Furthermore, rechallenge of tumor cells in the xenograft model has resulted in smaller tumor volume, which demonstrated that the combinational treatment enhanced the activity of memory T cells. Remarkably, this combinational therapy presented significant efficacy on multiple types of tumors as well and was able to prevent relapse of tumor partially. Taken together, our combinational immunotherapy provides a new avenue to enhance the clinical outcomes of patients who are insensitive or resistant to ICIs treatments.

The effect of depression and anxiety on survival in patients with glioma: a systematic review and meta-analysis.

PURPOSE: Depression and anxiety's impact on glioma patient survival lacks consensus. Understanding these effects can highlight the importance of identifying depression and anxiety in glioma patients, and inform future treatments. This systematic review and meta-analysis aims to clarify the impact of depression and anxiety on glioma patient survival. METHODS: We conducted a systematic literature search of major databases, including PubMed, Embase, Web of Science Core Collection, Cochrane Library, and PsycINFO, from inception to June 2023, to identify relevant studies. Eligible studies were those that examined the association between depression, anxiety, or both, and survival outcomes in glioma patients. Data were extracted and analyzed using fixed-effects meta-analysis models to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 15 studies met the inclusion criteria, encompassing a diverse range of glioma patients across different clinical settings and stages. The meta-analysis revealed a statistically significant association between depression and reduced overall survival in glioma patients, with a pooled HR of 1.65 (95% CI: 1.41-1.83, 11 studies). The preliminary univariate meta-regression results indicate no impact of individual study characteristics on the effect size. Likewise, anxiety was associated with worse overall survival, with a pooled HR of 1.65 (95% CI: 1.18-2.31, 5 studies). CONCLUSIONS: This meta-analysis underscores the vital need to identify and treat depression and anxiety in glioma patients. Future research should explore the underlying mechanisms, aiding the creation of interventions enhancing both mental health and clinical outcomes for this vulnerable group.