Polyamine Anabolism Promotes Chemotherapy-Induced Breast Cancer Stem Cell Enrichment.

Breast cancer patients may initially benefit from cytotoxic chemotherapy but experience treatment resistance and relapse. Chemoresistant breast cancer stem cells (BCSCs) play a pivotal role in cancer recurrence and metastasis, however, identification and eradication of BCSC population in patients are challenging. Here, an mRNA-based BCSC signature is developed using machine learning strategy to evaluate cancer stemness in primary breast cancer patient samples. Using the BCSC signature, a critical role of polyamine anabolism in the regulation of chemotherapy-induced BCSC enrichment, is elucidated. Mechanistically, two key polyamine anabolic enzymes, ODC1 and SRM, are directly activated by transcription factor HIF-1 in response to chemotherapy. Genetic inhibition of HIF-1-controlled polyamine anabolism blocks chemotherapy-induced BCSC enrichment in vitro and in xenograft mice. A novel specific HIF-1 inhibitor britannin is identified through a natural compound library screening, and demonstrate that coadministration of britannin efficiently inhibits chemotherapy-induced HIF-1 transcriptional activity, ODC1 and SRM expression, polyamine levels, and BCSC enrichment in vitro and in xenograft and autochthonous mouse models. The findings demonstrate the key role of polyamine anabolism in BCSC regulation and provide a new strategy for breast cancer treatment.

Modern perspectives of heavy metals alleviation from oil contaminated soil: A review.

Heavy metal poisoning of soil from oil spills causes serious environmental problems worldwide. Various causes and effects of heavy metal pollution in the soil environment are discussed in this article. In addition, this study explores new approaches to cleaning up soil that has been contaminated with heavy metals as a result of oil spills. Furthermore, it provides a thorough analysis of recent developments in remediation methods, such as novel nano-based approaches, chemical amendments, bioremediation, and phytoremediation. The objective of this review is to provide a comprehensive overview of the removal of heavy metals from oil-contaminated soils. This review emphasizes on the integration of various approaches and the development of hybrid approaches that combine various remediation techniques in a synergistic way to improve sustainability and efficacy. The study places a strong emphasis on each remediation strategy that can be applied in the real-world circumstances while critically evaluating its effectiveness, drawbacks, and environmental repercussions. Additionally, it discusses the processes that reduce heavy metal toxicity and improve soil health, taking into account elements like interactions between plants and microbes, bioavailability, and pollutant uptake pathways. Furthermore, the current study suggests that more research and development is needed in this area, particularly to overcome current barriers, improve our understanding of underlying mechanisms, and investigate cutting-edge ideas that have the potential to completely transform the heavy metal clean up industry.

Effect of electroacupuncture on myocardial transient receptor potential channels in mice with myocardial hypertrophy. / ç”µé’ˆå¯¹å¿ƒè‚Œè‚¥åŽšå°é¼ å¿ƒè‚Œç»„ç»‡çž¬æ—¶å—ä½“ç”µä½é€šé“çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Neiguan"(PC6) on cardiac function, cardiac morphology and transient receptor potential channel (TRPC) protein expressions in myocardial tissue of mice with myocardial hypertrophy, so as to explore its mechanisms underlying improvement of myocardial hypertrophy. METHODS: Forty-five male C57BL/6 mice were randomly divided into control, model and EA groups (15 mice/group). The myocardial hypertrophy model was established by subcutaneous injection of isoproterenol hydrochloride (15 mg·kg-1·d-1) for 14 days. The mice of the control group received subcutaneous injection of same amount of normal saline. The mice of the EA group received EA stimulation (frequency of 2 Hz, intensity of 1 mA) of bilateral PC6 for 20 min each time, once a day for 14 consecutive days. After the intervention, the body weight, tibia length and heart weight were measured. The left ventricular ejection fraction (EF), fractional shortening index (FS), left ventricular end-systolic volume (LVEV), left ventricular end-systolic internal diameter (LVID) and left ventricular posterior wall thickness (LVPW) were measured by using echocardiography for evaluating the cardiac function. The mean number and surface area of myocardial cells was detected by wheat germ agglutinin (WGA) staining, and changes of the cardiac morphology were observed under light microscopy after HE staining. The expression levels of TRPC1, TRPC3, TRPC4 and TRPC6 (TRPC1/3/4/6) in the myocardial tissue were detected by real-time quantitative PCR (qPCR) and Western blot, separately. RESULTS: Compared with the control group, the heart-body weight ratio(P<0.05) and heart-weight-to-tibia-length ratio (P<0.01), LVEV and LVID levels, the relative surface area, left ventricular area ratio, and the expression levels of cardiac TRPC1/3/4/6 were significantly increased (P<0.01, P<0.05), while the EF, FS, LVPW, number of cardiomyocytes, and the left ventricular posterior wall ratio were obviously decreased (P<0.01, P<0.05) in the model group. In comparison with the model group, the heart/body weight ratio, heart-weight-to-tibia-length ratio, LVEV and LVID levels, relative surface area, left ventricular area ratio, and the expression levels of cardiac TRPC1/3/4/6 were significantly decreased (P<0.01, P<0.05), while the EF, FS, LVPW, number of cardiomyocytes and left ventricular posterior wall ratio were significantly increased (P<0.01, P<0.05) in the EA group. H.E. staining showed disordered arrangement of cardiomyocytes and obvious myocardial interstitial inflammatory cell infiltration in the model group, and evident reduction of degree of cardiac fibrosis and interstitial edema in the EA group. CONCLUSIONS: EA of PC6 can improve the cardiac function and cardiac morphology in mice with myocardial hypertrophy, which may be related to its functions in down-regulating the expression of transient receptor potential channels.

Beyond success: unveiling the hidden potential of radiotherapy and immunotherapy in solid tumors.

Immunotherapy, particularly with immune checkpoint inhibitors, has significantly transformed cancer treatment. Despite its success, many patients struggle to respond adequately or sustain long-lasting clinical improvement. A growing consensus has emerged that radiotherapy (RT) enhances the response rate and overall efficacy of immunotherapy. Although combining RT and immunotherapy has been extensively investigated in preclinical models and has shown promising results, establishing itself as a dynamic and thriving area of research, clinical evidence for this combination strategy over the past five years has shown both positive and disappointing results, suggesting the need for a more nuanced understanding. This review provides a balanced and updated analysis of the combination of immunotherapy and RT. We summarized the preclinical mechanisms through which RT boosts antitumor immune responses and mainly focused on the outcomes of recently updated clinical trials, including those that may not have met expectations. We investigated the optimization of the therapeutic potential of this combined strategy, including key challenges, such as fractionation and scheduling, lymph node irradiation, and toxicity. Finally, we offered insights into the prospects and challenges associated with the clinical translation of this combination therapy, providing a realistic perspective on the current state of research and potential future directions.

Predictors of Adverse Pregnancy Outcomes Following Traumatic Injuries.

OBJECTIVE: After traumatic injury in pregnant women, providing timely and appropriate management for high-risk patients is crucial for both pregnant women and fetuses. This study aimed to identify risk factors that predict adverse pregnancy outcomes after traumatic injury. METHODS: A retrospective cohort study including 317 pregnant patients who experienced trauma was conducted. The collected data included general demographics, injury mechanisms and adverse pregnancy outcomes. Patients were divided into two subgroups based on the absence or presence of trauma-related adverse pregnancy outcomes. Univariate and multivariate logistic regressions were conducted to estimate the associations between clinical variables and adverse pregnancy outcomes. RESULTS: A total of 41 (12.93%) patients experienced adverse pregnancy outcomes within the first 24 h post-trauma. This study revealed that age >35 years (OR=14.995, 95% CI: 5.024-44.755, P<0.001), third trimester trauma (OR=3.878, 95% CI: 1.343-11.204, P=0.012), abdominal pain (OR=3.032, 95% CI: 1.221-7.527, P=0.017), vaginal bleeding (OR=3.226, 95% CI: 1.093-9.523, P=0.034), positive scan in focused assessment with sonography for trauma (FAST) positive (OR=8.496, 95% CI: 2.825-25.555, P<0.001), 9≤ injury severity score (ISS) <16 (OR=3.039, 95% CI: 1.046-8.835, P=0.041) and ISS≥16 (OR=5.553, 95% CI: 1.387-22.225, P=0.015) increased the probability of posttraumatic adverse pregnancy outcomes. Maternal age, gestational age at delivery, vaginal bleeding and positive FAST results were risk factors for abnormal delivery. CONCLUSION: Advanced maternal age, third trimester, and positive FAST results should alert multidisciplinary trauma teams to closely monitor patients to prevent adverse pregnancy outcomes.

Underlying beliefs of preventive health behaviours among women with a history of gestational diabetes mellitus: A descriptive qualitative study.

AIMS: To explore the underlying beliefs of preventive health behaviours among women with a history of GDM who had low levels of preventive health behaviours during their postpartum period in Singapore. METHODS: This paper reports on the qualitative arm of a mixed method study. The qualitative descriptive design was adopted. Individual interviews were conducted between 7th September 2020 and 25th September 2020 using a semi-structured interview guide. Data collected were analysed using thematic analysis. RESULTS: A total of 18 women completed the interview. The participants' ages ranged from 26 to 40 years with a mean age of 33.17 years (SD= 4.09). The duration since childbirth was 8.78 months (SD = 1.35). Through thematic analysis, five themes were developed: lifestyle adjustment, self-motivation, supportive environment, barriers to practising a healthy lifestyle, and risk perception. A total of 14 subthemes emerged from the five main themes. The beliefs of women with a history of GDM were described according to the Theory of Planned Behaviour. CONCLUSIONS: Having a newborn brings changes to the lifestyle of a woman and her family, which can affect the health behaviours in the postpartum period. This study revealed several novel findings relating to the unmet needs of women who had GDM, specifically to the need for information and emotional support to safely resume healthy behaviours after childbirth, for which participants have provided suggestions on how to enhance the continuity of care in the postpartum period.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) activates p38 to affect pulmonary fibrosis.

Objective: We aimed to examine whether heparin-binding epidermal growth factor-like growth factor (HB-EGF) affects the lung fibrosis process through the activation of p38 protein in mitogen-activated protein kinases (MAPK) signaling pathway, as well as the expression of downstream inflammatory factors. Methods: The expression levels of HB-EGF, collagen type I (COL-I), and hexokinase 2 (HK2) in peripheral blood mononuclear cells (PBMCs) of patients with connective tissue disease-related interstitial lung disease (CTD-ILD) were examined by qPCR, Western blotting and ELISA. Results: In vitro experiments showed that HB-EGF was increased in almost all subtypes [rheumatoid arthritis (RA), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIMs)] as well as in all groups (P < 0.05). For embryonic lung fibroblast (A549) cells, the expression levels of HK2 and α-smooth muscle actin (α-SMA) genes were elevated during 0-4 h and then plateaued. Transforming growth factor-ß1 (TGF-ß1) induced fibrosis in human embryonic lung fibroblasts (MRC-5) cells and A549 for a certain period of time, but the degree of induction varied, which may be related to the redifferentiability of cells at different spatial locations. Moreover, HB-EGF at concentrations above 1 ng/ml stimulation increased COL-I expression (P < 0.05), and for α-SMA gene, even 1 ng/ml concentration of HB-EGF had a stimulatory effect, and different concentrations of HB-EGF did activate the expression of p38 in a concentration-dependent manner within a certain concentration range, and by The qPCR results showed that for interleukin 6 (IL-6), an inflammatory factor regulated downstream of p38, the expression was significantly increased in A549 cells compared to control (P < 0.05), but tumor necrosis factor-α (TNF-α) expression was downregulated (P < 0.05), but for interleukin-1ß (IL-1ß) gene, there was no significant difference in A549 cells, and expression was downregulated in MRC-5 cells. Therefore, it is suggested that HB-EGF regulates the expression of inflammatory factors through p38 will be differential across cells. Conclusion: Our study shows that HB-EGF can suppress pulmonary fibrosis through downstream activation of p38/MAPK pathway activity, as well as the expression of various inflammatory factors downstream of it.

Chinese hospital staff in anxiety and depression: Not only comfort patients but also should be comforted - A nationwide cross-sectional study.

BACKGROUND: Healthcare professionals are in short supply worldwide, especially in China, which can result in increased stress in the work environment and allostatic load for Chinese hospital staff. This study aimed to investigate the prevalence of anxiety and depressive symptoms and their relationship with total stress, allostatic overload, sleep quality, and episodic memory among Chinese hospital staff. METHOD: In this cross-sectional study, self-assessments including Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire-9 (PHQ-9), PsychoSocial Index (PSI), Pittsburgh Sleeping Quality Index (PSQI), and MemTrax test were used to evaluate participants' anxiety symptoms, depressive symptoms, total stress, allostatic load/overload, sleep quality, and episodic memory. RESULTS: A total of 9433 hospital staff from 304 cities participated. Anxiety prevalence was 21.0 % (95 % confidential interval (CI) 20.2 %, 21.8 %), while the prevalence of depressive symptoms was at 21.4 % (95 % CI 20.5 %, 22.2 %). 79.8 % (95 % CI 79.0 %, 80.6 %) of the hospital staff had allostatic overload. Poor sleep quality affected 50.4 % of participants, and 32.1 % experienced poor episodic memory. LIMITATIONS: This study utilized a convenience sampling approach, relying on an online survey as its data collection method. CONCLUSIONS: Hospital staff in China are facing a stressful environment with a high prevalence of anxiety and depressive symptoms, significant allostatic overload, poor sleep quality, and compromised episodic memory. It is imperative that local management and community structures enhance their support and care for these essential workers, enabling them to manage and withstand the stresses of their professional roles effectively.

Cross-Sectional and Prospective Association of Serum 25-Hydroxyvitamin D with Gut Mycobiota during Pregnancy among Women with Gestational Diabetes.

SCOPE: Little is known about the effect of blood vitamin D status on the gut mycobiota (i.e., fungi), a crucial component of the gut microbial ecosystem. The study aims to explore the association between 25-hydroxyvitamin D [25(OH)D] and gut mycobiota and to investigate the link between the identified mycobial features and blood glycemic traits. METHODS AND RESULTS: The study examines the association between serum 25(OH)D levels and the gut mycobiota in the Westlake Precision Birth Cohort, which includes pregnant women with gestational diabetes mellitus (GDM). The study develops a genetic risk score (GRS) for 25(OH)D to validate the observational results. In both the prospective and cross-sectional analyses, the vitamin D is associated with gut mycobiota diversity. Specifically, the abundance of Saccharomyces is significantly lower in the vitamin D-sufficient group than in the vitamin D-deficient group. The GRS of 25(OH)D is inversely associated with the abundance of Saccharomyces. Moreover, the Saccharomyces is positively associated with blood glucose levels. CONCLUSION: Blood vitamin D status is associated with the diversity and composition of gut mycobiota in women with GDM, which may provide new insights into the mechanistic understanding of the relationship between vitamin D levels and metabolic health.

Emigration and fiscal gap in population-exporting region.

This paper analyzes how emigration impacts fiscal gap of population-exporting region in the long term. We construct a general equilibrium model of emigration and fiscal gap and make empirical verification using two-step system GMM model. Among the major lessons from this work, five general and striking results are worth highlighting: (1) the economic losses of emigration are the immediate cause of widening the fiscal gap. (2) in the short and long term, emigration can expand the fiscal revenue gap through the superimposed effect of tax rate and tax base. (3) the gap in fiscal expenditure is widened by the outflow of people in the short term. However, local governments would change the strategy to keep the spending gap from widening in the long run. (4) a positive impact of emigration on the fiscal gap. the more severe population emigration, the larger the fiscal gap. (5) when the trend of emigration becomes irreversible, the subsequent efforts of local governments to expand fiscal expenditure for attraction population would not only fail to revive the regional economy, but aggravate the expansion of fiscal gap. The contribution of research is twofold. On the one hand, it fills the theoretical gap between emigration and fiscal gap because previous studies have paid little attention to the fiscal problems of local government of population outflow. On the other hand, the selection of Northeast China that has been subject to long-term out-of-population migration is good evidence to verify this theory, which is tested very well using the 2S-GMM model. The comprehensive discussion on the relationship between emigration and fiscal gap is helpful to guide those continuous population-exporting regions that are facing a huge fiscal gap how to solve the fiscal gap and unsustainability from the perspective of fiscal revenue and expenditure.

Unsupervised Bidirectional Contrastive Reconstruction and Adaptive Fine-Grained Channel Attention Networks for image dehazing.

Recently, Unsupervised algorithms has achieved remarkable performance in image dehazing. However, the CycleGAN framework can lead to confusion in generator learning due to inconsistent data distributions, and the DisentGAN framework lacks effective constraints on generated images, resulting in the loss of image content details and color distortion. Moreover, Squeeze and Excitation channel attention employs only fully connected layers to capture global information, lacking interaction with local information, resulting in inaccurate feature weight allocation for image dehazing. To solve the above problems, in this paper, we propose an Unsupervised Bidirectional Contrastive Reconstruction and Adaptive Fine-Grained Channel Attention Networks (UBRFC-Net). Specifically, an Unsupervised Bidirectional Contrastive Reconstruction Framework (BCRF) is proposed, aiming to establish bidirectional contrastive reconstruction constraints, not only to avoid the generator learning confusion in CycleGAN but also to enhance the constraint capability for clear images and the reconstruction ability of the unsupervised dehazing network. Furthermore, an Adaptive Fine-Grained Channel Attention (FCA) is developed to utilize the correlation matrix to capture the correlation between global and local information at various granularities promotes interaction between them, achieving more efficient feature weight assignment. Experimental results on challenging benchmark datasets demonstrate the superiority of our UBRFC-Net over state-of-the-art unsupervised image dehazing methods. This study successfully introduces an enhanced unsupervised image dehazing approach, addressing limitations of existing methods and achieving superior dehazing results. The source code is available at https://github.com/Lose-Code/UBRFC-Net.

High-altitude hypoxia exposure inhibits erythrophagocytosis by inducing macrophage ferroptosis in the spleen.

High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen's ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.

MolProphet: A One-Stop, General Purpose, and AI-Based Platform for the Early Stages of Drug Discovery.

Artificial intelligence (AI) is an effective tool to accelerate drug discovery and cut costs in discovery processes. Many successful AI applications are reported in the early stages of small molecule drug discovery. However, most of those applications require a deep understanding of software and hardware, and focus on a single field that implies data normalization and transfer between those applications is still a challenge for normal users. It usually limits the application of AI in drug discovery. Here, based on a series of robust models, we formed a one-stop, general purpose, and AI-based drug discovery platform, MolProphet, to provide complete functionalities in the early stages of small molecule drug discovery, including AI-based target pocket prediction, hit discovery and lead optimization, and compound targeting, as well as abundant analyzing tools to check the results. MolProphet is an accessible and user-friendly web-based platform that is fully designed according to the practices in the drug discovery industry. The molecule screened, generated, or optimized by the MolProphet is purchasable and synthesizable at low cost but with good drug-likeness. More than 400 users from industry and academia have used MolProphet in their work. We hope this platform can provide a powerful solution to assist each normal researcher in drug design and related research areas. It is available for everyone at https://www.molprophet.com/.

Precise tooth design using deep learning-based templates.

OBJECTIVES: In prosthodontic procedures, traditional computer-aided design (CAD) is often time-consuming and lacks accuracy in shape restoration. In this study, we combined implicit template and deep learning (DL) to construct a precise neural network for personalized tooth defect restoration. METHODS: Ninety models of right maxillary central incisor (80 for training, 10 for validation) were collected. A DL model named ToothDIT was trained to establish an implicit template and a neural network capable of predicting unique identifications. In the validation stage, teeth in validation set were processed into corner, incisive, and medium defects. The defective teeth were inputted into ToothDIT to predict the unique identification, which actuated the deformation of the implicit template to generate the highly customized template (DIT) for the target tooth. Morphological restorations were executed with templates from template shape library (TSL), average tooth template (ATT), and DIT in Exocad (GmbH, Germany). RMSestimate, width, length, aspect ratio, incisal edge curvature, incisive end retraction, and guiding inclination were introduced to assess the restorative accuracy. Statistical analysis was conducted using two-way ANOVA and paired t-test for overall and detailed differences. RESULTS: DIT displayed significantly smaller RMSestimate than TSL and ATT. In 2D detailed analysis, DIT exhibited significantly less deviations from the natural teeth compared to TSL and ATT. CONCLUSION: The proposed DL model successfully reconstructed the morphology of anterior teeth with various degrees of defects and achieved satisfactory accuracy. This approach provides a more reliable reference for prostheses design, resulting in enhanced accuracy in morphological restoration. CLINICAL SIGNIFICANCE: This DL model holds promise in assisting dentists and technicians in obtaining morphology templates that closely resemble the original shape of the defective teeth. These customized templates serve as a foundation for enhancing the efficiency and precision of digital restorative design for defective teeth.

A positive association between RDW and coronary heart disease in the rheumatoid arthritis population: A cross-sectional study from NHANES.

Previous research has indicated that higher red blood cell distribution width (RDW) increases the risk of coronary heart disease. However, no studies have established a link between RDW and coronary heart disease in the rheumatoid arthritis population. This research aims to explore the association between RDW and coronary heart disease among individuals with rheumatoid arthritis. We selected demographic data, laboratory data, lifestyle, and medical history from the National Health and Nutrition Examination Survey (NHANES), specifically including age, gender, poverty, RDW, race, BMI, diabetes, education, coronary heart disease, hypertension, cholesterol, smoking, and drinking. RDW and coronary heart disease were found to have a positive association in the rheumatoid arthritis population (OR = 1.145, 95%CI: 1.036-1.266, P = .0098), even after adjusting for factors such as age, gender, race, education level, smoking, and drinking. Subgroup analysis showed a stronger positive association, particularly in individuals aged 55-66 years, males, and the Hispanic White population with diabetes or hypercholesterolemia. There is a significant correlation between RDW and coronary heart disease among individuals with rheumatoid arthritis.

Review on toxicology and activity of tomato glycoalkaloids in immature tomatoes.

Owing to the lack of selection and limited intelligence in mechanical picking, some immature tomatoes that contain alkaloids are thrown away. Tomatine alkaloids are steroidal alkaloids naturally present in Solanaceae plants, which are distributed in small amounts in immature tomato fruits and decrease as the fruits ripen. Tomato glycoalkaloids are harmful to human health. However, in small quantities, there is some evidence that these compounds might be beneficial, as other non-antioxidant bioactivities. This article considers recent research on the biological effects of tomato glycoalkaloids in immature tomatoes, providing reference value for the potential development of these compounds.

Advancing In-Depth N-Terminomics Detection with a Cleavable 2-Pyridinecarboxyaldehyde Probe.

Proteolysis, an irreversible post-translational modification catalyzed by proteases, plays a crucial role in various biological processes. Exploring abnormally hydrolyzed proteins in pathological tissues is a valuable approach for elucidating the mechanisms underlying disease development. Herein, we have developed a cleavable 2-pyridinecarboxyaldehyde probe (2PCA-Probe) that enables efficient and in-depth N-terminomics detection, addressing limitations of previous methods. Furthermore, we unexpectedly discovered a new marker capable of identifying N-terminal chemical labeling with the 2PCA-Probe and elucidated the reaction mechanism. Using this probe, we identified 4686 N-terminal peptides in colorectal cancer and adjacent tissues, significantly expanding the depth of the N-terminome and revealing the potential role of abnormal protein hydrolysis in colorectal cancer development.

Microbes translocation from oral cavity to nasopharyngeal carcinoma in patients.

The presence of oral microbes in extra-oral sites is linked to gastrointestinal cancers. However, their potential ectopically colonization in the nasopharynx and impact on local cancer development remains uncertain. Our study involving paired nasopharyngeal-oral microbial samples from nasopharyngeal carcinoma (NPC) patients and controls unveils an aberrant oral-to-nasopharyngeal microbial translocation associated with increased NPC risk (OR = 4.51, P = 0.012). Thirteen species are classified as oral-translocated and enriched in NPC patients. Among these, Fusobacterium nucleatum and Prevotella intermedia are validated through culturomics and clonal strain identification. Nasopharyngeal biopsy meta-transcriptomes confirm these microbes within tumors, influencing local microenvironment and cytokine response. These microbes correlate significantly with the Epstein-Barr virus (EBV) loads in the nasopharynx, exhibiting an increased dose-response relationship. Collectively, our study identifies oral microbes migrating to the nasopharynx, infiltrating tumors, impacting microenvironments and linking with EBV infection. These results enhance our understanding of abnormal microbial communication and their roles in carcinogenesis.