Auxin-producing bacteria promote barley rhizosheath formation.

The rhizosheath, or the layer of soil closely adhering to roots, can help plants to tolerate drought under moderate soil drying conditions. Rhizosheath formation is the result of poorly understood interactions between root exudates, microbes, and soil conditions. Here, we study the roles played by the soil microbiota in rhizosheath formation in barley (a dry crop). We show that barley rhizosheath formation is greater in acid soil than in alkaline soil, and inoculation with microbiota from acid soil enhances rhizosheath formation in alkaline soil. The rhizosheath-promoting activity is associated with the presence of Flavobacteriaceae and Paenibacillaceae bacteria that express genes for biosynthesis of indole-3-acetic acid (IAA, a common auxin), as determined by metagenomics and metatranscriptomics. Two bacterial strains isolated from rhizosheath (Chryseobacterium culicis and Paenibacillus polymyxa) produce IAA and enhance barley rhizosheath formation, while their IAA-defective mutants are unable to promote rhizosheath formation. Co-inoculation with the IAA-producing strains enhances barley grain yield in field experiments through an increase in spike number. Our findings contribute to our understanding of barley rhizosheath formation, and suggest potential strategies for crop improvement.

Oleoylethanolamide ameliorates motor dysfunction through PPARα-mediates oligodendrocyte differentiation and white matter integrity after ischemic stroke.

BACKGROUND AND AIM: Our previous study has revealed that OEA promotes motor function recovery in the chronic stage of ischemic stroke. However, the neuroprotective mechanism of OEA on motor function recovery after stroke still is unexplored. Therefore, the aim of this study was to explore the effects of OEA treatment on angiogenesis, neurogenesis, and white matter repair in the peri-infarct region after cerebral ischemia. EXPERIMENTAL PROCEDURE: The adult male rats were subjected to 2 h of middle cerebral artery occlusion. The rats were treated with 10 and 30 mg/kg OEA or vehicle daily starting from day 2 after ischemia induction until they were sacrificed. KEY RESULTS AND CONCLUSIONS: The results revealed that OEA increased cortical angiogenesis, neural progenitor cells (NPCs) proliferation, migration, and differentiation. OEA treatment enhanced the survival of newborn neurons and oligodendrogenesis, which eventually repaired the cortical neuronal injury and improved motor function after ischemic stroke. Meanwhile, OEA treatment promoted the differentiation of oligodendrocyte progenitor cells (OPCs) and oligodendrogenesis by activating the PPARα signaling pathway. Our results showed that OEA restores motor function by facilitating cortical angiogenesis, neurogenesis, and white matter repair in rats after ischemic stroke. Therefore, we demonstrate that OEA facilitates functional recovery after ischemic stroke and propose the hypothesis that the long-term application of OEA mitigates the disability after stroke.

Tirzepatide immunogenicity on pharmacokinetics, efficacy, and safety: analysis of data from Phase 3 studies.

CONTEXT: Anti-drug antibodies (ADA) can potentially affect drug pharmacokinetics, safety, and efficacy. OBJECTIVE: To evaluate treatment-emergent (TE) ADA in tirzepatide-treated participants across seven Phase 3 trials and their potential effect on pharmacokinetics, efficacy, and safety. DESIGN: ADA were assessed at baseline and throughout the study until endpoint, defined as week 40 (SURPASS 1, 2, and 5) or week 52 (SURPASS 3, 4, Japan-mono, and Japan-combo). SETTING: Samples for ADA characterization were collected at SURPASS trial sites. PARTICIPANTS: ADA-evaluable tirzepatide-treated patients with type 2 diabetes (N=5025). INTERVENTIONS: Tirzepatide 5, 10, or 15 mg. MAIN OUTCOME MEASURES: ADA were detected and characterized for their ability to cross react with native GIP (nGIP) and GLP-1 (nGLP-1), neutralize tirzepatide activity on GIP and GLP-1 receptors, and neutralize nGIP and nGLP-1. RESULTS: TE ADA developed in 51.1% of patients. Proportions were similar across dose groups. Maximum ADA titers ranged from 1:20 to 1: 81920 among TE ADA+ patients. Neutralizing antibodies (NAb) against tirzepatide activity on GIP and GLP-1 receptors were observed in 1.9% and 2.1% of TE ADA+ patients, respectively. Less than 1.0% of tirzepatide-treated TE ADA+ patients had cross-reactive NAb against nGIP or nGLP-1. TE ADA status, ADA titer, and NAb had no impact on pharmacokinetics or efficacy of tirzepatide. More TE ADA+ tirzepatide-treated patients experienced hypersensitivity reactions or injection site reactions than TE ADA- patients. The majority of hypersensitivity and injection site reactions were nonserious and non-severe, and most events occurred and/or resolved irrespective of TE ADA status or titer. CONCLUSIONS: Immunogenicity did not impact tirzepatide pharmacokinetics or efficacy. Majority hypersensitivity or injection site reactions experienced by TE ADA+ patients were mild to moderate in severity.

Efficacy and safety of olmesartan medoxomil-amlodipine besylate tablet in Chinese patients with essential hypertension: A prospective, single-arm, multi-center, real-world study.

There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

Confined Heterojunction in Hollow-Structured TiO2 and Its Directed Effect in Photodriven Seawater Splitting.

The high salinity of seawater often strongly affects the activity and stability of photocatalysts utilized for photodriven seawater splitting. The current investigation is focused on the photocatalyst H-TiO2/Cu2O, comprised of hydroxyl-enriched hollow mesoporous TiO2 microspheres containing incorporated Cu2O nanoparticles. The design of H-TiO2/Cu2O is based on the hypothesis that the respective hollow and mesoporous structure and hydrophilic surfaces of TiO2 microspheres would stabilize Cu2O nanoparticles in seawater and provide efficient and selective proton adsorption. H-TiO2/Cu2O shows hydrogen production performances of 45.7 mmol/(g·h) in simulated seawater and 17.9 mmol/(g·h) in natural seawater, respectively. An apparent quantum yield (AQY) in hydrogen production of 18.8% in water (and 14.9% in natural seawater) was obtained at 365 nm. Moreover, H-TiO2/Cu2O displays high stability and can maintain more than 90% hydrogen evolution activity in natural seawater for 30 h. A direct mass- and energy- transfer mechanism is proposed to clarify the superior performance of H-TiO2/Cu2O in seawater splitting.

Detection of African Swine Fever Virus from Wild Boar, Singapore, 2023.

We detected African swine fever virus (ASFV) from a wild boar in Singapore. In <72 hours, we confirmed and reported ASFV p72 genotype II, CD2v serogroup 8, and IGR-II variant by using a combination of real-time PCR and whole-genome sequencing. Continued biosurveillance will be needed to monitor ASFV in Singapore.

Three-dimensional power sparse code division non-orthogonal multiple access scheme with constellation pair mapping.

This paper proposes a three-dimensional power sparse code division non-orthogonal multiple access (3D-PSCD-NOMA) scheme with 3D constellation pair mapping. The proposed sparse code is based on a balanced incomplete block design (BIBD). Its correlation matrix performs the overall signal mapping of multi-user information. Power multiplexing is realized by overlaying multi-level power signals with different path losses through pair mapping. Compared with the conventional 2D standard square 32 Quadrature Amplitude Modulation (QAM), the proposed 3D constellation pair mapping can improve the constellation points' minimum Euclidean distance (MED) by 17.7%, which is beneficial for the performance of the system. Based on obtaining the optimal power distribution ratio (PDR) for different schemes, a 3D-PSCD-NOMA signal with a rate of 15.22 Gb/s over a 25 km single-mode fiber (SMF) is experimentally performed. The experimental results show that 3D-PSCD-NOMA has a clear superiority. At the same rate, 3D-PSCD-NOMA2 can obtain a sensitivity gain of about 1.6 dB and 1.9 dB over the conventional 2D constellation. Moreover, 3D-PSCD-NOMA reduces the system's peak-to-average power ratio (PAPR) by 1.3 dB. The difference in sensitivity of the system before and after sparse code is about 0.15 dB, and no significant degradation occurred. Due to its advantages in transmission performance, 3D-PSCD-NOMA is a potential solution for future optical access systems.

Electrically controllable broadband reflective linear cross-polarization conversion based on liquid crystals.

This paper presents an electrically controllable reflective broadband linear polarization (LP) converter based on liquid crystals (LCs) for cross-polarization conversion (CPC) in the terahertz frequency range. The proposed structure achieves a high polarization conversion ratio (PCR) exceeding 0.9 within the frequency range of 236.8 - 269.6 GHz. A vital feature of this design is the dynamic control of polarization conversion by re-orienting the nematic liquid crystal molecules through voltage bias switching between 'on' and 'off' states, allowing for precise manipulation of cross-polarized and co-polarized reflected waves. Experimental results validate the simulation outcomes, demonstrating excellent agreement. In contrast to conventional reflective polarization converters with fixed frequency responses, the proposed electrically controllable polarization conversion offers significant potential in imaging and optical communications.

LSR targets YAP to modulate intestinal Paneth cell differentiation.

Lipolysis-stimulated lipoprotein receptor (LSR) is a multi-functional protein that is best known for its roles in assembly of epithelial tricellular tight junctions and hepatic clearance of lipoproteins. Here, we investigated whether LSR contributes to intestinal epithelium homeostasis and pathogenesis of intestinal disease. By using multiple conditional deletion mouse models and ex vivo cultured organoids, we find that LSR elimination in intestinal stem cells results in the disappearance of Paneth cells without affecting the differentiation of other cell lineages. Mechanistic studies reveal that LSR deficiency increases abundance of YAP by modulating its phosphorylation and proteasomal degradation. Using gain- and loss-of-function studies, we show that LSR protects against necrotizing enterocolitis through enhancement of Paneth cell differentiation in small-intestinal epithelium. Thus, this study identifies LSR as an upstream negative regulator of YAP activity, an essential factor for Paneth cell differentiation, and a potential therapeutic target for necrotizing enterocolitis.

Genetic Predisposition, Sedentary Behavior and Incident Coronary Artery Disease: A Prospective Chinese Cohort Study.

PURPOSE: Whether the association of sedentary behaviors with coronary artery disease (CAD) can be influenced by genetic susceptibility remains unclear. We aimed to investigate the joint and interplay effects between genetic risk and sedentary time (ST), and further explore the extent to which the risk for CAD can be counteracted by reducing ST in different genetic groups. METHODS: This prospective cohort study included 39,164 Chinese adults without CAD history. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants, and daily ST was assessed by questionnaire. We analyzed the modification effect of genetic risk on the association of ST with CAD using the Cox proportional hazards models. RESULTS: During a median follow-up of 11.60 years, 1156 CAD events were documented.Higher ST and PRS were separately related to elevated CAD risk. Significant additive interaction was also observed (relative excess risk due to interaction: 0.77; 95%CI: 0.27-1.28). Compared with participants with low genetic risk and low ST (<6 h/day), those with high genetic risk and high ST (≥10 h/day) had the highest CAD risk, with the hazard ratio (HR) and 95% confidence interval (95%CI) of 4.22 (2.65-6.71). When stratified by genetic risks, participants with high ST had gradient increment of CAD risks across low, intermediate, and high genetic risk groups, with the HR (95%CI) of 1.21 (0.61-2.40), 1.57 (1.14-2.16), and 2.15 (1.40-3.31), respectively. For the absolute risk reduction, individuals with high genetic risk achieved the greatest benefit from low ST (Ptrend = 0.024). CONCLUSIONS: Genetic susceptibility may synergistically interact with ST to increase CAD risk. Reducing ST could attenuate the CAD risk, especially among individuals with high genetic risk.

MIZ1 acts downstream of PGM1 in regulating root hydrotropism.

The MIZ1 play an important role in root hydrotropism. However, the relationship between MIZ1-regulated hydrotropism and amyloplast-mediated gravitropism remain largely unclear. Here, we generated the miz1/pgm1 double mutants by crossing the non-hydrotropic miz1 mutant with the amyloplast-defective pgm1 mutant, which lacks gravitropic response. Our results showed that the miz1/pgm1 mutants exhibited a significant reduction in amyloplast and gravitropic bending, while maintaining a similar ahydrotropic phenotype as the miz1 single mutant. These findings suggest that MIZ1 plays a role in hydrotropism downstream of PGM1. Understanding the mechanisms of interaction between hydrotropism and gravitropism is crucial for comprehending the rooting patterns of plants in natural conditions. The counteracting relationship between root hydrotropism and gravitropism in the miz1 mutant should receive attention in this field, particularly considering the interference from gravitropism on Earth.

ABA is required for differential cell wall acidification associated with root hydrotropic bending in tomato.

Hydrotropism is an important adaptation of plant roots to the uneven distribution of water, with current research mainly focused on Arabidopsis thaliana. To examine hydrotropism in tomato (Solanum lycopersicum) primary roots, we used RNA sequencing to determine gene expression of root tips (apical 5 mm) on dry and wet sides of hydrostimulated roots grown on agar plates. Hydrostimulation enhances cell division and expansion on the dry side compared with the wet side of the root tip. In hydrostimulated roots, the abscisic acid (ABA) biosynthesis gene ABA4 was induced more on the dry than the wet side of root tips. The ABA biosynthesis inhibitor Fluridone and the ABA-deficient mutant notabilis (not) significantly decreased hydrotropic curvature. Wild-type, but not the ABA biosynthesis mutant not, root tips showed asymmetric H+ efflux, with greater efflux on the dry than on the wet side of root tips. Thus, ABA mediates asymmetric H+ efflux, allowing the root to bend towards the wet side to take up more water.

Broad-spectrum vaccine via combined immunization routes triggers potent immunity to SARS-CoV-2 and its variants.

Developing broad-spectrum vaccines and optimal vaccination strategies is crucial to controlling the COVID-19 pandemic. Here, we generated a chimpanzee adenoviral vector-based COVID-19 vaccine carrying broad-spectrum immunogens, modified full-length spike, and conserved T-cell epitopes of SARS-CoV-2, and assessed its immune response in mice through intramuscular (i.m.), intranasal (i.n.), or combined immunization routes (i.m. + i.n., or i.n. + i.m.). Compared to other vaccination strategies, the two combined regimens elicited higher neutralizing antibody (NAb) responses to all variants. Compared to i.n. + i.m. regimen, the i.m. + i.n. regimen stimulated a stronger secondary GC response, which is more pivotal to high-quality antibody production than the primary GC response. Moreover, the i.m. + i.n. regimen was adept at mediating systemic cellular immunity, while the i.n. + i .m. regimen tended to elicit lung tissue-resident memory T (TRM) cell responses. Overall, the two combined regimens induced comprehensive but distinct immune responses consisting of lgA, lgG, NAbs, GC B cells, long-lived plasma cells, TRM cells, and systemic memory T cells, which conferred complete protection against BA.2 infection in hACE2 transgenic mice, and warranted further investigation as potential universal vaccination strategies. IMPORTANCE The development of broad-spectrum SARS-CoV-2 vaccines will reduce the global economic and public health stress from the COVID-19 pandemic. The use of conserved T-cell epitopes in combination with spike antigen that induce humoral and cellular immune responses simultaneously may be a promising strategy to further enhance the broad spectrum of COVID-19 vaccine candidates. Moreover, this research suggests that the combined vaccination strategies have the ability to induce both effective systemic and mucosal immunity, which may represent promising strategies for maximizing the protective efficacy of respiratory virus vaccines.

Magnetic field caused enhanced absorption and circular dichroism of an achiral plasmonic nanostructure.

In this paper, modulation of light-matter interactions by a magnetic field is used to generate circular dichroism (CD) from an achiral plasmonic nanostructure. Theoretical investigations show an increase in light absorption by the nanostructure in the presence of a magnetic field. The achiral nanostructure exhibits CD in external magnetic field parallel to circularly polarized light (CPL) incidence. The CD emergence is caused by modulation of electron motion to reduced/enhanced frequencies under CPL incidence. Compared to previous studies, in this paper the mechanism of CD emergence, and the physical reasoning behind the change in CD due to change in magnetic field direction and intensity, are explained. CD intensity increases with increasing magnetic field intensity, while CD sign changes on magnetic field direction reversal. Varying structural parameters significantly influences CD intensity. This study can be helpful in magneto-optics and in magneto-chiral applications.

Spatio-temporal distribution and overlap of Naemorhedus griseus and Capricornis milneedwardsii in Gongga Mountain, Sichuan, China.

Clarifying the distribution pattern and overlapping relationship of sympatric relative species in the spatio-temporal niche is important for our understanding of the behavioral relationship between species and the integrated management of multi-species habitats. Based on the infrared camera monitoring data from 2012 to 2021, we investigted the spatio-temporal distribution characteristics of the national secondary-class key protected animals Naemorhedus griseus and Capricornis milneedwardsii in the Gongga Mountain National Nature Reserve, Sichuan Province. We analyzed the distribution of N. griseuss and C. milneedwardsiis in the reserve using the MaxEnt model, based on 72 and 108 occurrence data of the two species, respectively, obtained by infrared cameras from 2016 to 2021, combined with 12 environmental factors potentially affecting their spatial distribution. Then, based on 1312 occurrence data of N. griseus and 1889 occurrence data of C. milneedwardsii collected by infrared camera from 2012 to 2021, we estimated their daily activity rhythms by using the kernel density estimation to understand the distribution pattern and overlap of the two species in the temporal niche. The results showed that the area of suitable habitats for N. griseus and C. milneedwardsii was 731.95 km2 and 1220.46 km2, respectively. The overlapping area was 697.17 km2. The main environmental factors had similar effects on the habitat selection of the two species. The daily activity of both species peaked in the early morning and evening. The utilization of the interval and intensity of the morning and evening time periods were different for the two species. The morning and evening activity peaks of C. milneedwardsii were earlier and later, respectively, than that of N. griseus. C. milneedwardsii had a higher utilization intensity during the nocturnal period. In general, high degree of spatial overlap and low degree of overlap in the temporal niche dimension contribute to the long-term coexistence of the two species.

Effect of low-temperature stress on the survival of Meloidogyne incognita and its application in greenhouse of northern China.

We examined the effects of low temperature on egg hatching and killing rate of the 2nd instars of Meloi-dogyne incognita (J2) in the laboratory. We further evaluated the effects of two soil treatment methods on the survival rate of M. incognita in northern China in a field experiment. The results of laboratory experiment showed that survival rate of J2 was 0 after being subjected to -7 ℃ for 24 hours, and that egg hatching was completely inhibited 24 hours after being subjected to -9 ℃. The survival rate of J2 was 0 after being subjected to -1, -2, -3, and -4 ℃ for 8, 5, 3, and 1.5 d, respectively. Egg hatching was completely inhibited after being subjected to -2, -3, -4, and -5 ℃ for 9, 6, 4, and 1 d, respectively. Results of the fitting analysis showed that both the relationships between the temperature and the lethal time of J2 as well as the temperature and the non-hatching time of the eggs followed exponential functions. The results of field test showed that death rate of M. incognita in 0-50 cm soil layer after ridging treatment and 0-30 cm soil layer after leveling treatment could reach 100%, while the disease index of the former in 30-40 cm and 40-50 cm was 84.9% and 75.8%, respectively, which was lower than that in the greenhouse. Our results suggest that preventing and controlling M. incognita in greenhouses through low-tempe-rature in winter could achieve a better control effect in Yulin City and the northward region. The proposed technique is convenient and has high potential for popularization.

Improving the developmental competences of porcine parthenogenetic embryos by Notoginsenoside R1-induced enhancement of mitochondrial activity and alleviation of proapoptotic events.

Notoginsenoside R1 (NGR1), derived from the Panax notoginseng root and rhizome, exhibits diverse pharmacological influences on the brain, neurons, and osteoblasts, such as antioxidant effects, mitochondrial function protection, energy metabolism regulation, and inhibition of oxygen radicals, apoptosis, and cellular autophagy. However, its effect on early porcine embryonic development remains unclear. Therefore, we investigated NGR1's effects on blastocyst quality, reactive oxygen species (ROS) levels, glutathione (GSH) levels, mitochondrial function, and embryonic development-related gene expression in porcine embryos by introducing NGR1 during the in vitro culture (IVC) of early porcine embryos. Our results indicate that an addition of 1 µM NGR1 significantly increased glutathione (GSH) levels, blastocyst formation rate, and total cell number and proliferation capacity; decreased ROS levels and apoptosis rates in orphan-activated porcine embryos; and improved intracellular mitochondrial distribution, enhanced membrane potential, and reduced autophagy. In addition, pluripotency-related factor levels were elevated (NANOG and octamer-binding transcription factor 4 [OCT4]), antioxidant-related genes were upregulated (nuclear factor-erythroid 2-related factor 2 [NRF2]), and apoptosis- (caspase 3 [CAS3]) and autophagy-related genes (light chain 3 [LC3B]) were downregulated. These results indicate that NGR1 can enhance early porcine embryonic development by protecting mitochondrial function.

The hepatitis B virus pre-core protein p22 suppresses TNFα-induced apoptosis by regulating the NF-κB pathway.

OBJECTIVE: Cell apoptosis is strongly associated with hepatocellular carcinoma (HCC) progress. Thus, gaining a comprehensive understanding of the virus interfering with the apoptotic process is important for the development of effective anti-tumor therapies. The objective of this study is to explore the potential involvement of HBeAg-p22 (HBV-p22) in TNFα-induced apoptosis. METHODS: Protein expression was detected using western blot. Cell viability and apoptosis were assessed by employing Cell Counting Kit-8 (CCK8) and flow cytometry, respectively. Evaluation of protein-protein interactions was accomplished through co-immunoprecipitation and glutathione-S-transferase (GST) pull-down assays. RESULTS: In this study, it was shown that HBV-p22 inhibited apoptosis of human hepatoma cell lines after tumor necrosis factor-alpha (TNF-α) stimulation. Mechanistically, HBV-p22 suppressed Jun N-terminal kinases (JNK) signaling and enhanced nuclear factor kappa-B (NF-κB) signaling. Moreover, HBV-p22 interacted with I-kappa B kinase α (IKKα) and increased its phosphorylation. CONCLUSIONS: Collectively, HBV-p22, whereby the mechanism contributing to anti-apoptotic effect was regulation of the NF-κB pathway via enhancing the phosphorylation of IKKα.

Colorectal cancer cell-secreted exosomal miRNA N-72 promotes tumor angiogenesis by targeting CLDN18.

Angiogenesis is essential for the growth and metastasis of several malignant tumors including colorectal cancer (CRC). The molecular mechanism underlying CRC angiogenesis has not been fully elucidated. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the intercellular communication between tumor cells and neighboring endothelial cells to regulate tumor angiogenesis. In addition, exosomes have been shown to carry and deliver miRNAs to regulate angiogenesis. miRNA N-72 is a novel miRNA that plays a regulatory role in the EGF-induced migration of human amnion mesenchymal stem cells. However, the relation between miRNA N-72 and cancer remains unclear. We here found that CRC cells could secrete miRNA N-72. A high miRNA N-72 level was detected in the serum of CRC patients and the cultured CRC cells. Moreover, the CRC cell-secreted miRNA N-72 could promote the migration, tubulogenesis, and permeability of endothelial cells. In addition, the mouse xenograft model was used to verify the facilitating effects of miRNA N-72 on CRC growth, angiogenesis, and metastasis in vivo. Further mechanism analysis revealed that CRC cell-secreted miRNA N-72 could be delivered into endothelial cells via exosomes, which then inhibited cell junctions of endothelial cells by targeting CLDN18 and consequently promoted angiogenesis. Our findings reveal a novel mechanism of CRC angiogenesis and highlight the potential of secreted miRNA N-72 as a therapeutic target and a biomarker for CRC.