Ultrasensitive proteomics depicted an in-depth landscape for the very early stage of mouse maternal-to-zygotic transition

Single-cell or low-input multi-omics techniques have revolutionized the study of pre-implantation embryo development.However,the single-cell or low-input proteomic research in this field is relatively underdeveloped because of the higher threshold of the starting material for mammalian embryo samples and the lack of hypersensitive proteome technology.In this study,a comprehensive solution of ultrasensitive proteome technology(CS-UPT)was developed for single-cell or low-input mouse oocyte/embryo samples.The deep coverage and high-throughput routes significantly reduced the starting material and were selected by investigators based on their demands.Using the deep coverage route,we provided the first large-scale snapshot of the very early stage of mouse maternal-to-zygotic transition,including almost 5,500 protein groups from 20 mouse oocytes or zygotes for each sample.Moreover,significant protein regulatory networks centered on transcription factors and kinases between the MII oocyte and 1-cell embryo provided rich insights into minor zygotic genome activation.

Landscape of urine biomarkers for bladder cancer:molecular function,cell-of-origin,and bibliometric trend

Background:The effective management of bladder cancer(BCa)depends on the early diagnosis and surveillance.Previous studies have explored numerous urinary molecules as potential biomarkers of BCa.However,the molecular functions and cell-of-origin profiles of these biomarkers are yet to be elucidated.In this study,we aimed to provide a comprehensive overview of the landscape of urinary biomarker genes for BCa.Methods:We conducted an exhaustive literature search in PubMed,through which 555 biomarker genes were identified.We then analyzed the BCa single-cell atlas to infer the cellular origin of these BCa urine biomarker genes and performed functional enrichment analysis to gain insights into the functional molecular implications of these biomarkers.Results:These genes are involved in tumor proliferation,angiogenesis,cellmigration,and cell death and are predominantly expressed in epithelial and stromal cells.Interestingly,our analysis ofmultiomics tumor data revealed a discordance between tissue and urine in terms of differential methylation and RNA expression,suggesting that biomarker discovery for liquid biopsies should ideally begin with the analysis of bodily fluids rather than relying interest and that test strategies incorporating multiple molecular markers represent an ongoing trend.Conclusions:Collectively,our study has built a landscape of BCa urine biomarker genes,uncovered molecular insights into these biomarkers,and revealed the bibliometric trends in this field,which will contribute to the discovery of novel biomarkers in the future.

Exosomal CD44 Cooperates with Integrin a6b4 to Support Organotropic Metastasis via Regulating Tumor Cell Motility and Target Host Cell Activation

Rapid metastasis to vital organs such as the lung,liver,and brain is responsible for the vast majority of pancreatic cancer deaths.Liver metastasis of pancreatic cancer accounts for the high mortality rate in patients.Exosomes derived from pancreatic cancer cells tend to be enriched in proteins that are anchored to the cell membrane,supporting the reprogramming of the tumor microenvironment and the progression of distant metastatic lesions.For the first time,our study has demonstrated that cluster of differentiation 44(CD44),a transmembrane glycoprotein delivered by exosomes,is involved in the metastatic process of pancreatic cancer.Moreover,CD44 was found to interact with integrin a6b4 to form a complex,thereby remodeling intracellular skeleton proteins,and to promote tumor cell motility through the activation of the Src and Ras signaling cascades.Notably,we also demonstrated that the CD44–a6b4 complex can be delivered to the target region via the paracrine effects of exosomes.The selective uptake of CD44-competent tumor exosomes by liver cells activated fibrotic pathways and generated a pre-metastatic niche by stimulating the cytokines,proinflammatory factors,and growth factors that ultimately support tumor metastasis.Our results suggest the potential application of exosomal CD44 as a biomarker for the clinical diagnosis of and therapy for pancreatic cancer.

Oral Microbiota:A New Insight into Cancer Progression,Diagnosis and Treatment

The polymorphic microbiome has been defined as one of the“Hallmarks of Cancer”.Extensive studies have now uncovered the role of oral microbiota in cancer development and progression.Bacteria,fungi,archaea,and viruses in the oral cavity interact dynamically with the oral microenvironment to maintain the oral micro-ecological homeostasis.This complex interaction is influenced by many factors,such as maternal transmission,personal factors and environmental factors.Dysbiosis of oral microbiota can disturbed this host-microbiota interaction,leading to systemic diseases.Numerous studies have shown the potential associations between oral microbiota and a variety of cancers.However,the underlying mechanisms and therapeutic insights are still poorly understood.In this review,we mainly focus on the following aspects:(1)the factors affect oral microbiota composition and function;(2)the interaction between microenvironment and oral microbiota;(3)the role of multi-kingdom oral microbiota in human health;(4)the potential underlying mechanisms and therapeutic benefits of oral microbiota against cancer.Finally,we aim to describe the impact of oral microbiota on cancer progression and provide novel therapeutic insights into cancer prevention and treatment by targeting oral microbiota.

Benzo[a]pyrene stimulates miR-650 expression to promote the pathogenesis of fatty liver disease and hepatocellular carcinoma via SOCS3/JAK/STAT3 cascades

Modern diets,which often feature high levels of fat and charcoal-grilled meat,contribute to the pathogenesis of obesity and non-alcoholic fatty liver disease(NAFLD),resulting in liver cancer progression.Benzo(a)pyrene(B[a]P)is a common environ-mental and foodborne pollutant found in smoke and fire-grilled foods,which can have an adverse effect on human health.Hepatocellular carcinoma(HCC)is the fifth leading cause of cancer and the second leading cause of cancer-related deaths worldwide.The epidemiological studies suggest that both environmental risk factors and chronic liver injury including NAFL are important for HCC development,but the precise mechanisms linking eating habits to hepato-carcinogenesis remain unclear.In the present study,we demonstrated that various miRNAs in B[a]P-exposed tumor cells contribute to tumor metastasis,among which miR-650 could be the most potent inducer.Furthermore,we found that the suppressor of cytokine signaling 3(SOCS3)is directly regulated by miR-650 and its suppression regulates the activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3)cascade.Our findings reveal a possible adverse outcome pathway of SOCS3/JAK/STAT3 regulation in B[a]P-induced HCC progress.These results provide a better understanding of the adverse effects of chronic exposure to B[a]P on human health.

Kinase-substrate Edge Biomarkers Provide a More Accurate Prognostic Prediction in ER-negative Breast Cancer

The estrogen receptor(ER)-negative breast cancer subtype is aggressive with few treatment options available.To identify specific prognostic factors for ER-negative breast cancer,this study included 705,729 and 1034 breast invasive cancer patients from the Surveillance,Epidemiology,and End Results(SEER)and The Cancer Genome Atlas(TCGA)databases,respectively.To identify key differential kinase-substrate node and edge biomarkers between ER-negative and ERpositive breast cancer patients,we adopted a network-based method using correlation coefficients between molecular pairs in the kinase regulatory network.Integrated analysis of the clinical and molecular data revealed the significant prognostic power of kinase-substrate node and edge features for both subtypes of breast cancer.Two promising kinase-substrate edge features,CSNK1A1-NFATC3 and SRC-OCLN,were identified for more accurate prognostic prediction in ERnegative breast cancer patients.

A Novel Prognostic Biomarker LPAR6 in Hepatocellular Carcinoma via Associating with Immune Infiltrates

Background and Aims:LPAR6 is the most recently deter-mined G protein-coupled receptor of lysophosphatidic acid,and hardly any study has demonstrated the performance of LPAR6 in cancers.We sought to clarify the relationship of LPAR6 to prognosis potential and tumor infiltration im-mune cells in different cancers.Methods:The expression of LPAR6 and its clinical characteristics were evaluated on various databases.The association between LPAR6 and im-mune infiltrates of various types of cancer were investigated via TIMER.Results:We determined that higher LPAR6 ex-pression level was associated with a better overall survival.Additionally,high LPAR6 expression level was significantly associated with better disease-specific survival(DSS)in bladder cancer,and better overall survival(OS)/progres-sion-free survival(PFS)/distant metastasis-free survival(DMFS)/relapse-free survival(RFS)in breast cancer and some other types of cancers.Moreover,LPAR6 significant-ly affects the prognosis of various cancers via The Cancer Genome Atlas(TCGA).Further research exposed that the mRNA level of LPAR6 was positively coordinated with in-filtrating levels of devious immune cells in hepatocellular carcinoma.Conclusions:Our results imply that LPAR6 is associated with prognosis potential and immune infiltration levels in liver cancer.Moreover,LPAR6 expression possibly contributes to the activation of CD8+T,naive T,effector T cells and natural killer cells and inactivates T regulatory cells,decreases T cell exhaustion and regulate T helper cells in liver cancer.These discoveries imply that LPAR6 could be a novel biomarker of prognosis for indicating progno-sis potential and immune-infiltrating level in hepatocellular carcinoma.

Comments on ‘An airway organoid-based screen identifies a role for the HIF1α‒glycolysis axis in SARS-CoV-2 infection’

Coronavirus disease 2019(COVID-19)has been an ongoing public health crisis since the end of 2019;besides vaccine development,there have been major research efforts focused on developing antiviral therapeutics.Remdesivir was the first US Food and Drug Administration(FDA)-approved antiviral drug for COVID-19.Subsequently,the FDA granted emergency use authorization(EUA)for three monoclonal antibody treatments,including sotrovimab or a combination of casirivimab and imdevimab,or bamlanivimab and etesevimab,each of which targets the coronavirus spike protein to block viral entry.Most recently,Britain granted conditional authorization for the ribonucleoside analog molnupiravir,developed by Merck as a viral replication inhibitor.The protease inhibitor PF-07321332 developed by Pfizer and boosted by ritonavir showed promising results in a phase III clinical trial,reducing the risk of hospitalization or death by 89%compared with placebo.