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Claudin 18.2 (CLDN18.2), a tight junction protein isoform, is an emerging therapeutic target in oncology. CLDN18 is well‐characterized in gastric cancer, but its pan‐cancer expression profiles and isoform distributions are poorly documented. In the present study, we analyzed CLDN18 expression in patients with solid tumors enrolled in the MONSTAR‐SCREEN‐2 study using immunohistochemistry (IHC, n = 349) and whole‐transcriptome sequencing (WTS, n = 2191). A splice junction analysis algorithm characterized isoform distribution patterns in WTS data and evaluated temporal changes using paired pre‐ and postchemotherapy specimens. IHC detected CLDN18.2 (≥ 40% of tumor cells showing any staining intensity) in 16.3% of patients, with highest prevalence in gastric (54.5%), biliary tract (21.7%), pancreatic (20.7%), and small intestinal (18.2%) cancers. WTS and IHC findings were significantly correlated (p < 0.001). WTS analysis with optimized transcript thresholds (n = 2191) demonstrated the CLDN18‐high population to be 13.8%, with highest proportions in gastric (64.5%), small intestinal (40.0%), pancreatic (37.8%), and biliary tract (20.0%) cancers. Isoform analysis of 364 patients revealed CLDN18.2 predominance (mean 18.2/18.1 proportion 0.945), with CLDN18.1 predominance observed in only 4.9% of patients. Longitudinal analysis of 27 paired gastric cancer samples revealed a significant reduction in CLDN18 expression and a nonsignificant decrease in the CLDN18.2 proportion following chemotherapy. This analysis validates WTS as a complementary approach to IHC for CLDN18 assessment and demonstrates significant CLDN18 expression across multiple cancer types. The predominance of CLDN18.2 supports the expansion of targeted therapeutic approaches beyond gastric cancer and indicates the potential of RNA‐based screening.

Aim Perioperative neurocognitive disorders (PND) occur frequently after surgery and anesthesia, especially in aged patients. Previous studies have shown multiple PND related mechanisms in the hippocampus; however, their relationships remain unclear. Meanwhile, the perioperative neuropathological processes are sophisticated and changeable, single period study could not reveal the accurate mechanisms. Thus, multiperiod whole‐transcriptome study is necessary to elucidate the gene expression patterns during perioperative period. Methods Aged C57BL/6 mice were subjected to exploratory laparotomy under sevoflurane anesthesia. Whole‐transcriptome sequencing (RNA‐seq analysis) was performed on the hippocampi from control condition (Con), 30 min (Day0), 2 days (Day2), and 7 days (Day7) after surgery. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses, quantitative real‐time PCR, immunofluorescence, and fear conditioning test were also performed to elucidate the pathological processes and modulation networks during the period. Results Through RNA‐seq analysis, 328, 3597, and 4179 differentially expressed genes (DEGs) were screened out in intraoperative period (Day0 vs. Con), early postoperative period (Day2 vs. Day0), and late postoperative period (Day7 vs. Day2). The involved GO biological processes were divided into 9 categories, and positive‐regulated processes were more than negative‐regulated ones. Seventy‐four transcription factors were highlighted. The potential synaptic and neuroinflammatory pathways were constructed for Neurotransmitter, Synapse and Neuronal alteration categories with 9 genes (Htr1a, Rims1, and Ezh2, etc.). The metabolic and mitochondrial pathways were constructed for metabolism, oxidative stress, and biological rhythm categories with 9 genes (Gpld1, Sirt1, and Cry2, etc.). The blood–brain barrier and neurotoxicity related pathways were constructed for blood–brain barrier, neurotoxicity, and cognitive function categories with 10 genes (Mmp2, Itpr1, and Nrf1, etc.). Conclusion The results revealed gene expression patterns and modulation networks in the aged hippocampus during perioperative period, which provide insights into overall mechanisms and potential therapeutic targets for prevention and treatment of perioperative central nervous system diseases, such as PND, from the genetic level. Whole‐transcriptome sequencing reveals gene expression patterns in the aged hippocampus during perioperative period. The involved pathological processes include neuroinflammation, metabolism, and blood–brain barrier alteration, neurotoxicity, etc., which have changeable status and exert distinct roles during intraoperative, early and late postoperative periods. These results provide insights for the major mechanisms and therapeutic targets of perioperative neurocognitive disorders.

PIGA mutation cannot fully explain the proliferative advantage of abnormal clones and thrombosis tendency in paroxysmal nocturnal haemoglobinuria (PNH), and additional genes may play a role, justifying further investigation. CD59+ and CD59‐ peripheral blood mononuclear cells from six PNH patients were sorted and subjected to whole‐exon sequencing (WES) and whole‐transcriptome sequencing respectively. Six age‐ and sex‐matched healthy volunteers were enrolled as controls. Genes related to proliferation, immunity and thrombosis were selected by gene ontology (GO) analysis. The selected gene mutant alleles were then identified in the WES results for 40 patients and verified by the Sanger method in another 40 PNH patients. CD59+ and CD59‐ peripheral blood mononuclear cells from seven patients were sorted, and the RNA and protein expression levels of target genes were assessed via quantitative real‐time PCR (RT‐qPCR), flow cytometry and western blotting. The final selected genes were then related to clinical features to analyse. T‐cell activation–related genes were upregulated, whereas platelet degranulation, coagulation, haemostasis, leukocyte proliferation and platelet activation–related genes were downregulated in both CD59+ and CD59‐ cells. The mRNA or protein expression levels of SELP, FLT1, NRP1 and vWF were either different from those in healthy controls or different between CD59+ and CD59‐ cells. Moreover, platelet aggregation was greater in patients with mutations in these genes than in patients without such mutations. Except for PIGA, other genes may be involved in the proliferation and coagulopathy that occur in PNH patients.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by dysregulated immune responses, resulting in sustained inflammation and ulceration of the colonic and rectal mucosa. To elucidate the cellular subtypes and gene expression profiles implicated in the pathogenesis of UC, we utilized single-cell and spatial transcriptomic analyses. We conducted an analysis of single-cell data to identify cell types involved in the pathogenesis of UC. Employing machine learning methodologies, we screened for key genes implicated in UC and validated these findings through spatial transcriptomics. Additionally, immunohistochemistry was performed on UC lesion samples to investigate the expression patterns of the identified key genes. In an animal model, we utilized immunofluorescence and western blotting to validate the expression of these genes in the affected intestinal segments. Our investigation identified specific monocyte subtypes associated with UC through a comprehensive analysis involving cell communication, Least Absolute Shrinkage and Selection Operator (LASSO), and Support Vector Machine (SVM) methodologies. Notably, two genes, G protein subunit gamma 5 ( ) and tissue inhibitor of metalloproteinase 1 ( ), were identified as key regulators of UC development. Spatial transcriptomic indicated a downregulation of expression in UC, whereas expression was upregulated. Furthermore, a significant correlation was detected between and T cell exhaustion-related genes such as genes related to T cell exhaustion, including T cell immunoreceptor with Ig and ITIM domains ( ) and cytotoxic T-lymphocyte-associated protein 4 ( ). Immunohistochemical analysis of UC lesion samples revealed diminished expression levels of and elevated expression levels of . A dextran sulfate sodium (DSS)-induced colitis mouse model was developed, demonstrating that the protein expression levels of in the colonic tissue of model mice were significantly decreased compared to controls w)ile the expression levels of were increased ( < 0.01). Furthermore, immunofluorescence staining indicated co-localization of with the macrophage marker F4/80 in monocytes. Our research delineated distinct monocyte subtypes correlated with UC and identified two pivotal genes, and , that contribute to the disease's pathogenesis. These insights offer a significant theoretical basis for enhancing the clinical diagnosis and therapeutic strategies for patients with UC.

“Omics” typically involves exploration of the structure and function of the entire composition of a biological system at a specific level using high-throughput analytical methods to probe and analyze large amounts of data, including genomics, transcriptomics, proteomics, and metabolomics, among other types. Genomics characterizes and quantifies all genes of an organism collectively, studying their interrelationships and their impacts on the organism. However, conventional transcriptomic sequencing techniques target population cells, and their results only reflect the average expression levels of genes in population cells, as they are unable to reveal the gene expression heterogeneity and spatial heterogeneity among individual cells, thus masking the expression specificity between different cells. Single-cell transcriptomic sequencing and spatial transcriptomic sequencing techniques analyze the transcriptome of individual cells in plant or animal tissues, enabling the understanding of each cell’s metabolites and expressed genes. Consequently, statistical analysis of the corresponding tissues can be performed, with the purpose of achieving cell classification, evolutionary growth, and physiological and pathological analyses. This article provides an overview of the research progress in plant single-cell and spatial transcriptomics, as well as their applications and challenges in plants. Furthermore, prospects for the development of single-cell and spatial transcriptomics are proposed.

Salivary adenoid cystic carcinoma (SACC) is an intractable malignant tumor originates in the secretory glands and frequently metastasizes to the lungs. Hybrid epithelial‐mesenchymal transition (EMT) cells within the tumors are correlated with augmented proliferative capacity and facilitation of lung metastasis. Single‐cell RNA sequencing and spatial transcriptomic sequencing are employed to reveal the hybrid EMT subsets within the vascular fibroblast microenvironment. These hybrid EMT cells exhibit a pro‐tumorigenic impact in vitro. Notably, cadherin 11 (CDH11), a specific marker for hybrid EMT cells, may exert its regulatory role in cellular function by interfering with branched‐chain amino acids (BCAA) metabolism by inhibiting branched‐chain ketoacid dehydrogenase to activate the mammalian target of the rapamycin pathway, thus making it a potential therapeutic target for SACC. Furthermore, celecoxib and its derivatives are specific CDH11 inhibitors that regulate BCAA metabolism, increase reactive oxygen species production, and subsequently activate the cyclic GMP‐AMP synthase‐stimulator of the interferongene pathway (cGAS‐STING). They also inhibit lung metastasis in NOD‐SCID mice in vivo. Overall, these findings suggest a promising treatment strategy that targets hybrid EMT cells to mitigate lung metastasis in SACC. Celecoxib may serve as a promising clinical intervention for the treatment of lung metastases in patients with SACC. The highly expressed CDH11 in hybrid EMT cells may be a potential therapeutic target for SACC. CXB and its derivatives, as specific inhibitors of CDH11, modulate BCAA metabolism, enhance ROS production, and subsequently activate the cGAS‐STING pathway. In vitro, celecoxib and its derivatives inhibit SACC lung metastasis in NOD‐SCID mice.

Ovarian dysfunction is a major factor leading to female infertility. Understanding how to improve or reshape ovarian function has become an important entry point for preventing and treating female infertility caused by ovarian dysfunction. Here, plant‐derived compounds are screened for in vitro activity upon ovarian organoids derived from feeder‐free female germline stem cells. Tetrahydroxy stilbene glucoside (TSG) is found to promote the development of ovarian organoids. Single nucleus transcriptome sequencing and spatial transcriptome sequencing are used to establish a comprehensive spatiotemporal map to elucidate the role of TSG in ovarian organoid development, encompassing cell types and subtypes, transcription factors, pseudo‐time sequence, and cell communication dynamics. This analysis indicates that TSG promotes ovarian organoid development through the vascular endothelial growth factor A‐Eph receptor B2 ligand‐receptor pair between granulosa cells and oocytes. This study has enhanced the understanding of the mechanisms of ovarian organoid development, establishes a technical platform for screening compounds for treating infertility and related diseases, and lays a foundation for clinically applying plant‐derived compounds. The screening of plant‐derived compounds on ovarian organoids derived from feeder‐free female germline stem cells finds that tetrahydroxy stilbene glucoside (TSG) promotes follicle development and steroid hormone synthesis. Mechanistically, ST‐seq and snRNA‐seq reveal that TSG promotes ovarian organoid development through the vascular endothelial growth factor A‐Eph receptor B2 ligand‐receptor pair between granulosa cells and oocytes.

Understanding the environmental and genetic mechanisms underlying locally adaptive trait variation across the ranges of species is a major focus of evolutionary biology. Combining transcriptome sequencing with common garden experiments on populations spanning geographical and environmental gradients holds promise for identifying such mechanisms. The South African shrub Protea repens displays diverse phenotypes in the wild along drought and temperature gradients. We grew plants from seeds collected at 19 populations spanning this species’ range, and sequenced the transcriptomes of these plants to reveal gene pathways associated with adaptive trait variation. We related expression in co‐expressed gene networks to trait phenotypes measured in the common garden and to source population climate. We found that expression in gene networks correlated with source‐population environment and with plant traits. In particular, the activity of gene networks enriched for growth related pathways correlated strongly with source site minimum winter temperature and with leaf size, stem diameter and height in the garden. Other gene networks with enrichments for photosynthesis related genes showed associations with precipitation. Our results strongly suggest that this species displays population‐level differences in gene expression that have been shaped by source population site climate, and that are reflected in trait variation along environmental gradients.

Traditional biomaterial design often prioritizes empirical knowledge over disease mechanisms and pathological dynamics, resulting in imprecise solutions in complex clinical conditions. Age‐related osteoporosis (A‐OP) is a disease associated with aging, characterized by a dysfunctional pathological microenvironment that hinders the osseointegration of conventional titanium implants. To develop a targeted titanium implant for A‐OP, rat single‐cell transcriptomics is integrated with human serum‐derived transcriptome data to investigate dynamic changes in skeletal stem cells (SSCs) during aging, which guided the implant design. These findings reveal that hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) within SSCs interact via a feedback loop: HSCs undergo premature senescence, leading to depletion of HSCs and secondary senescence of MSCs. Senescent MSCs exhibit adipogenic bias, perpetuating the pathological cycle of A‐OP. Using core genes identified in the transcriptome analyses, resveratrol is selected and utilized it and a GelMA‐chitosan hydrogel to decorate titanium implants for localized delivery. In the A‐OP microenvironment, the hydrogel enables sustained responsive release of resveratrol, which reverses MSC senescence and redirects differentiation from adipogenic to osteogenic lineages, thereby breaking the pathological cycle. This multi‐omics‐driven implant design enhances precision and offers a novel methodology for biomaterial development. Senescent mesenchymal stromal cells (MSCs) drive age‐related osteoporosis (A‐OP) via adipogenic bias. Resveratrol, selected from transcriptome‐identified core genes, is delivered locally using GelMA‐chitosan hydrogel‐functionalised titanium implants. In A‐OP microenvironments, the hydrogel enables the sustained release of resveratrol, which reverses MSC senescence and redirects differentiation from the adipogenic to the osteogenic lineage. This breaks the pathological cycle of A‐OP.

Background Cholangiocarcinoma is a common hepatic malignant tumor with an unfavorable prognosis. Therefore, we systematically evaluated the transcriptomic landscape of CHOL by whole transcriptome sequencing technology in this study and constructed a ceRNA network associated with CHOL. Methods First, whole transcriptome sequencing between the tumor tissues of CHOL and adjacent cancer tissues adjacent to the tumors from six patients with CHOL was performed. Then, a differential expression analysis between the CHOL group and adjacent cancer group was performed to screen significant markers. Subsequently, target gene predictive analysis and co‐expression analysis were implemented to construct a ceRNA and protein–protein interaction network in CHOL, and enrichment analysis was performed to investigate gene‐related molecular pathways. Results The results showed that there were 761 differentially expressed mRNAs, 47 differentially expressed miRNAs, 61 differentially expressed lncRNAs, and 1481 differentially expressed circRNAs in the adjacent cancer group compared with the CHOL group, respectively. Enrichment analysis of differentially expressed mRNAs showed that the PI3K‐Akt, calcium, and MAPK signaling pathways were significantly enriched. Hsa‐miR‐196b‐5p can be a sponge to adsorb lncRNA H19 and 101 downregulated mRNAs, constructing an lncRNA‐miRNA‐mRNA network. Hsa_circ_0025636, hsa_circ_0057335, hsa‐miR‐96‐5p, and hsa‐miR‐196b‐5p were involved in the circRNA‐miRNA‐mRNA network. Moreover, five core genes were obtained through PPI interaction analysis, which also played an important role in the ceRNA network. Conclusions This study systematically presents a transcriptomic landscape of CHOL and identifies lncRNA/circRNA‐associated ceRNA networks that could provide insights for future treatment and prognosis of CHOL, laying a certain foundation for the study of molecular mechanisms and providing novel ideas for its prognosis and treatment.