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+Abstract 1:
+the gut mycobiota is crucial for intestinal homeostasis and immune function<sup>1</sup>. yet its variability and inconsistent fungal colonization of laboratory mice hinders the study of the evolutionary and immune processes that underpin commensalism<sup>2,3</sup>. here, we show that kazachstania pintolopesii is a fungal commensal in wild urban and rural mice, with an exceptional ability to colonize the mouse gastrointestinal tract and dominate the gut mycobiome. kazachstania pintolopesii colonization occurs in a bacteria-independent manner, results in enhanced colonization resistance to other fungi and is shielded from host immune surveillance, allowing commensal presence. following changes in the mucosal environment, k. pintolopesii colonization triggers a type 2 immune response in mice and induces gastrointestinal eosinophilia. mechanistically, we determined that k. pintolopesii activates type 2 immunity via the induction of epithelial il-33 and downstream il-33-st2 signalling during mucus fluctuations. kazachstania pintolopesii-induced type 2 immunity enhanced resistance to helminth infections or aggravated gastrointestinal allergy in a context-dependent manner. our findings indicate that k. pintolopesii is a mouse commensal and serves as a valuable model organism for studying gut fungal commensalism and immunity in its native host. its unnoticed presence in mouse facilities highlights the need to evaluate its influence on experimental outcomes and phenotypes.
+
+Abstract 2:
+brain-wide association studies (bwas) are a fundamental tool in discovering brain-behaviour associations<sup>1,2</sup>. several recent studies have shown that thousands of study participants are required for good replicability of bwas<sup>1-3</sup>. here we performed analyses and meta-analyses of a robust effect size index using 63 longitudinal and cross-sectional mri studies from the lifespan brain chart consortium<sup>4</sup> (77,695 total scans) to demonstrate that optimizing study design is critical for increasing standardized effect sizes and replicability in bwas. a meta-analysis of brain volume associations with age indicates that bwas with larger variability of the covariate and longitudinal studies have larger reported standardized effect size. analysing age effects on global and regional brain measures from the uk biobank and the alzheimer's disease neuroimaging initiative, we showed that modifying study design through sampling schemes improves standardized effect sizes and replicability. to ensure that our results are generalizable, we further evaluated the longitudinal sampling schemes on cognitive, psychopathology and demographic associations with structural and functional brain outcome measures in the adolescent brain and cognitive development dataset. we demonstrated that commonly used longitudinal models, which assume equal between-subject and within-subject changes can, counterintuitively, reduce standardized effect sizes and replicability. explicitly modelling the between-subject and within-subject effects avoids conflating them and enables optimizing the standardized effect sizes for each separately. together, these results provide guidance for study designs that improve the replicability of bwas.
+
+Abstract 3:
+cd8<sup>+</sup> t cells exhibit remarkable phenotypic diversity in inflammation and cancer. however, a comprehensive understanding of their clonal landscape and dynamics remains elusive. here we introduce scatlasvae, a deep-learning-based model for the integration of large-scale single-cell rna sequencing data and cross-atlas comparisons. scatlasvae has enabled us to construct an extensive human cd8<sup>+</sup> t cell atlas, comprising 1,151,678 cells from 961 samples across 68 studies and 42 disease conditions, with paired t cell receptor information. through incorporating information in t cell receptor clonal expansion and sharing, we have successfully established connections between distinct cell subtypes and shed light on their phenotypic and functional transitions. notably, our approach characterizes three distinct exhausted t cell subtypes and reveals diverse transcriptome and clonal sharing patterns in autoimmune and immune-related adverse event inflammation. furthermore, scatlasvae facilitates the automatic annotation of cd8<sup>+</sup> t cell subtypes in query single-cell rna sequencing datasets, enabling unbiased and scalable analyses. in conclusion, our work presents a comprehensive single-cell reference and computational framework for cd8<sup>+</sup> t cell research.
+
+Abstract 4:
+targeted spatial transcriptomic methods capture the topology of cell types and states in tissues at single-cell and subcellular resolution by measuring the expression of a predefined set of genes. the selection of an optimal set of probed genes is crucial for capturing the spatial signals present in a tissue. this requires selecting the most informative, yet minimal, set of genes to profile (gene set selection) for which it is possible to build probes (probe design). however, current selections often rely on marker genes, precluding them from detecting continuous spatial signals or new states. we present spapros, an end-to-end probe set selection pipeline that optimizes both gene set specificity for cell type identification and within-cell type expression variation to resolve spatially distinct populations while considering prior knowledge as well as probe design and expression constraints. we evaluated spapros and show that it outperforms other selection approaches in both cell type recovery and recovering expression variation beyond cell types. furthermore, we used spapros to design a single-cell resolution in situ hybridization on tissues (scrinshot) experiment of adult lung tissue to demonstrate how probes selected with spapros identify cell types of interest and detect spatial variation even within cell types.
+
+Abstract 5:
+immunotherapy targeting programmed cell death-1 (pd-1) and pd-l1 immune checkpoints has reshaped treatment paradigms across several cancers, including breast cancer. combining pd-1/pd-l1 immune checkpoint blockade (icb) with chemotherapy has shown promising efficacy in both early and metastatic triple-negative breast cancer, although only a subset of patients experiences durable responses. identifying responders and optimizing immune drug selection are therefore critical. the effectiveness of pd-1/pd-l1 immunotherapy depends on both tumor-intrinsic factors and the extrinsic cell-cell interactions within the tumor microenvironment (tme). this review systematically summarizes the key findings from clinical trials of icbs in breast cancer and examines the mechanisms underlying pd-l1 expression regulation. we also highlight recent advances in identifying potential biomarkers for pd-1/pd-l1 therapy and emerging evidence of tme alterations following treatment. among these, the quantity, immunophenotype, and spatial distribution of tumor-infiltrating lymphocytes stand out as promising biomarkers. additionally, we explore strategies to enhance the effectiveness of icbs in breast cancer, aiming to support the development of personalized treatment approaches tailored to the unique characteristics of each patient's tumor.
+
+Abstract 6:
+t helper 2 (th2) cells orchestrate immunity against parasite infection and promote tissue repair but promote pathology in asthma and tissue fibrosis. here, we examined the mechanisms driving pathogenic differentiation of th2 cells. single-cell analyses of cd4<sup>+</sup> t cells from asthma and chronic rhinosinusitis patients revealed high expression of the hypoxia-inducible factor (hif)2α in th2 cells. in mice, hif2α deficiency impaired th2 differentiation and alleviated asthmatic inflammation. single-cell and lineage tracing approaches delineated a differentiation trajectory from tcf1<sup>+</sup>ly108<sup>+</sup> stem-like th2 cells to the st2<sup>+</sup>cd25<sup>+</sup> pathogenic progeny, depending on a hif2α-gata3 circuit that modulated phospholipid metabolism and t cell receptor (tcr)-phosphatidylinositol 3-kinase (pi3k)-protein kinase b (akt) activation via transcriptional regulation of the inositol polyphosphate multikinase (ipmk). overexpression of ipmk in hif2α-deficient cells promoted phosphatidylinositol (3,4,5)-trisphosphate (pip<sub>3</sub>) synthesis and pathogenic th2 cell differentiation, whereas pharmacological inhibition of hif2α impaired pathogenic differentiation of th2 cells and mitigated airway inflammation. our findings provide insight into the contextual cues that promote th2-mediated pathology and suggest hif2α as a therapeutic target in asthma.
+
+Abstract 7:
+car-macrophage has promising prospect in treating solid tumors, due to its high infiltration into tumors, and its dual roles in phagocytosis and immune modulation. here we show the clinical results of car-macrophage treatment of two ovarian cancer patients. the car-macrophages were produced by introducing a mesothelin targeting car to patients' primary peripheral blood mononuclear cell-derived macrophages, and the products were infused to patients intravenously. our data show good safety of the infusion product, and the efficacy can be further improved. intraperitoneal infusion of car-macrophages has proven effective in treating intraperitoneal tumors in a preclinical model, paving the way for demonstrating proof-of-concept clinical efficacy of car-macrophages in the treatment of intraperitoneal tumors.
+
+Abstract 8:
+liquid biopsies, in particular, analysis of cell-free dna, are expected to revolutionize the current landscape of cancer diagnostics and treatment. however, the existing methods for cfdna-based liquid biopsies for cancer have certain limitations, such as fragment interruption and gc bias, which are likely to be resolved by the emerging oxford nanopore technologies (ont), characterized by long read-length, fast read-times, high throughput, and polymerase chain reaction-free. in this review, we summarized the current literatures regarding the feasibility and applications of cfdna-based liquid biopsies using ont for cancer management, a possible game-changer that we believe is promising in detecting multimodal biomarkers and can be applied in a wide range of oncology utilities including early screening, diagnosis, and treatment monitoring.
+
+Abstract 9:
+cancer vaccines have garnered attention as a potential treatment for cancer metastases. nevertheless, the clinical response rate to vaccines remains < 30%. nanoparticles stabilize vaccines and improve antigen recognition and presentation, resulting in high tumor penetration or accumulation, effective co-distribution of drugs to the secondary lymphatic system, and adaptable antigen or adjuvant administration. such vaccine-like nanomedicines have the ability to eradicate the primary tumors as well as to prevent or eliminate metastases. this review examines state-of-the-art nanocarriers developed to deliver tumor vaccines to metastases, including synthetic, semi-biogenic, and biogenic nanosystems. moreover, it highlights the physical and pharmacological properties that enhance their anti-metastasis efficiency. this review also addresses the combination of nanovaccines with cancer immunotherapy to target various steps in the metastatic cascade, drawing insights from preclinical and clinical studies. the review concludes with a critical analysis of the challenges and frameworks linked to the clinical translation of cancer nanovaccines.
+
+Abstract 10:
+this review summarizes the existing information on the concentration of h<sup>+</sup> (ph) in vertebrate retinae and its changes due to various reasons. special features of h<sup>+</sup> homeostasis that make it different from other ions will be discussed, particularly metabolic production of h<sup>+</sup> and buffering. the transretinal distribution of extracellular h<sup>+</sup> concentration ([h<sup>+</sup>]<sub>o</sub>) and its changes under illumination and other conditions will be described in detail, since [h<sup>+</sup>]<sub>o</sub> is more intensively investigated than intracellular ph. in vertebrate retinae, the highest [h<sup>+</sup>]<sub>o</sub> occurs in the inner part of the outer nuclear layer, and decreases toward the rpe, reaching the blood level on the apical side of the rpe. [h<sup>+</sup>]<sub>o</sub> falls toward the vitreous as well, but less, so that the inner retina is acidic to the vitreous. light leads to complex changes with both electrogenic and metabolic origins, culminating in alkalinization. there is a rhythm of [h<sup>+</sup>]<sub>o</sub> with h<sup>+</sup> being higher during circadian night. extracellular ph can potentially be used as a signal in intercellular volume transmission, but evidence is against ph as a normal controller of fluid transport across the rpe or as a horizontal cell feedback signal. pathological and experimentally created conditions (systemic metabolic acidosis, hypoxia and ischemia, vascular occlusion, excess glucose and diabetes, genetic disorders, and blockade of carbonic anhydrase) disturb h<sup>+</sup> homeostasis, mostly producing retinal acidosis, with consequences for retinal blood flow, metabolism and function.
+