Inhibition of mPGES-2 ameliorates NASH by activating NR1D1 via heme.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD), a complex metabolic syndrome, has limited therapeutic options. Microsomal prostaglandin E synthase-2 (mPGES-2) was originally discovered as a prostaglandin E 2 (PGE 2 ) synthase; however, it does not produce PGE 2 in the liver. Moreover, the role of mPGES-2 in NAFLD remains undefined. Herein, we aimed to determine the function and mechanism of mPGES-2 in liver steatosis and steatohepatitis. APPROACH AND RESULTS: To evaluate the role of mPGES-2 in NAFLD, whole-body or hepatocyte-specific mPGES-2-deficient mice fed a high-fat or methionine-choline-deficient diet were used. Compared with control mice, mPGES-2-deficient mice showed reduced hepatic lipid accumulation, along with ameliorated liver injury, inflammation, and fibrosis. Furthermore, the protective effect of mPGES-2 deficiency against NAFLD was dependent on decreased cytochrome P450 4A14 and increased acyl-CoA thioesterase 4 levels regulated by the heme receptor nuclear receptor subfamily 1 group D member 1 (NR1D1), but not PGE 2 . Heme regulated the increased NR1D1 activity mediated by mPGES-2 deficiency. Further, we confirmed the protective role of the mPGES-2 inhibitor SZ0232 in NAFLD therapy. CONCLUSION: Our study indicates the pathogenic role of mPGES-2 and outlines the mechanism in mediating NAFLD, thereby highlighting the therapeutic potential of mPGES-2 inhibition in liver steatosis and steatohepatitis.

Absolute quantification of 2-hydroxyglutarate on tissue by matrix-assisted laser desorption/ionization mass spectrometry imaging for rapid and precise identification of isocitrate dehydrogenase mutations in human glioma.

Isocitrate dehydrogenase (IDH) gene mutations are important predictive molecular markers to guide surgical strategy in brain cancer therapy. Herein, we presented a method using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) for absolute quantification of 2-hydroxyglutarate (2-HG) on tissues to identify IDH mutations and evaluate tumor residue. This analytical method was tested among 34 glioma patients and validated with gold standard clinical technologies. The cut-off value of 2-HG was set as 0.81 pmol/µg to identify IDH mutant (IDHmt) gliomas with 100% specificity and sensitivity. In addition, 2-HG levels and tumor cell density (TCD) showed positive correlation in IDHmt gliomas by this spatial method. This MALDI MSI-based absolute quantification method has great potentiality for incorporating into surgical workflow in the future.

Sterilization of Escherichia coli by Photothermal Synergy of WO3-x/C Nanosheet under Infrared Light Irradiation.

The application of photocatalytic sterilization technology for the sterilization of water has been broadly studied in recent years. However, developing photocatalysts with high disinfection efficiency remains an urgent challenge. Tungsten trioxide with coexisting oxygen vacancies and carbon coating (WO3-x/C) has been successfully synthesized toward the photothermal inactivation of Escherichia coli. Oxygen vacancies and carbon coating bring WO3-x/C strong absorption in the infrared region and enhance the carrier separation efficiency. As a result, a higher sterilization rate is obtained compared to WO3. WO3-x/C can completely inactivate E. coli under infrared light within 40 min through photothermal synergy process. During the process of inactivating bacteria over WO3-x/C, E. coli is killed by the destruction of their cell membrane to decrease the activity of enzymes and release the cell contents, which can be ascribed to the efficient generation of reactive oxygen species (O2•- and •OH) and thermal effect. This work demonstrates a novel approach for engineering efficient and energy-saving catalysts for water sterilization.

Effects of Photoperiod on Acetaminophen-Induced Hepatotoxicity in Mice.

PURPOSE: Acetaminophen (APAP) is a clinically popular analgesic and antipyretic drug, but excessive APAP can cause fatal hepatotoxicity. Many factors affect the degree of APAP-induced liver injury. This study aimed to investigate how circadian rhythm affects the development of APAP-induced hepatotoxicity and to clarify the roles of photoperiod and dietary rhythm on APAP-induced hepatotoxicity in mice. METHODS: APAP-induced hepatotoxicity models were established by intraperitoneal injection of APAP (400 mg/kg) to mice. The mice were then divided into three treatment groups: normal diet, reversed diet, and reversed photoperiod. RESULTS: More severe liver injury was observed at zeitgeber time 12 (ZT12) than at zeitgeber time 0 (ZT0) in all treatment groups, suggesting that photoperiod played a critical role in APAP-induced liver injury. We observed a change in the expression of the circadian gene Per2, which may be responsible for regulation of liver injury by photoperiod. Our results showed negligible change in Per2 expression with diet reversion, whereas Cry1, Cry2, and Dbp expressions were more highly affected by diet reversion than was Per2 expression. Downstream effects including liver enzyme expression, GSH level, and inflammation factors were also examined to identify the mechanism of liver injury. The results indicated that the circadian gene Per2 participated in APAP biometabolism by regulating the expression of Cyp2e1, which may explain the more severe hepatotoxicity at ZT12 than at ZT0. CONCLUSION: APAP-induced hepatotoxicity can be mediated by photoperiod through the circadian gene Per2, suggesting that medicines containing APAP should be administered not only with food but also according to the appropriate photoperiod.

Microsomal prostaglandin E synthase 2 deficiency is resistant to acetaminophen-induced liver injury.

Acetaminophen (APAP)-induced liver injury is the main cause of acute liver failure. This study investigated the role of microsomal prostaglandin E synthase 2 (mPGES-2), discovered as one of the prostaglandin E2 (PGE2) synthases, in mediating APAP-induced liver injury. Using mPGES-2 wild-type (WT) and knockout (KO) mice, marked resistance to APAP-induced liver damage was found in mPGES-2 KO, as indicated by robust improvement of liver histology, changes in liver enzyme release, and marked decrease in APAP-cysteine adducts (APAP-CYS) and inflammatory markers. Moreover, the results confirmed that increase in liver PGE2 content in KO mice under basal conditions was not critical for the protection from APAP-induced liver injury. Importantly, mPGES-2 deletion inhibited the production of malondialdehyde (MDA), increasing glutathione (GSH) level. Enhanced GSH level may contribute to the inhibition of APAP toxicity in mPGES-2 KO mice. To further elucidate the role of mPGES-2 in the liver injury induced by APAP, adeno-associated viruses (AAV) were used to overexpress mPGES-2 in the liver. The results showed that mPGES-2 overexpression aggravates liver injury associated with an increase in inflammatory markers and chemokines after APAP treatment. Moreover, a lower level of GSH was detected in the mPGES-2 overexpression group compared to the control group. Collectively, our findings indicate that mPGES-2 plays a critical role in regulating APAP-induced liver injury, possibly by regulating GSH and APAP-CYS level, which may provide a potential therapeutic strategy for the prevention and treatment of APAP-induced liver injury.

Cp*CoIII-Catalyzed Synthesis of Pyrido[2',1':2,3]pyrimido[1,6-a]indol-5-iums via Tandem C-H Activation and Subsequent Annulation from 1-(Pyridin-2-yl)-1H-indoles and Internal Alkynes.

A Cp*CoIII-catalyzed C2-selective C-H alkenylation/annulation cascade transformation of 1-(pyridin-2-yl)-1H-indoles with internal alkynes to afford pyrido[2',1':2,3]pyrimido[1,6-a]indol-5-iums is presented. Moreover, 6,7-dihydro-4H-pyrido[2',1':2,3]pyrimido[1,6-a]indole, a new functionalized N-fused indole core heterocycle, could be constructed effectively via reduction of pyrido[2',1':2,3]pyrimido[1,6-a]indol-5-ium by NaBH4.

Interfacial electronic modulation of NiCo decorated nano-flowered MoS2 on carbonized wood as a remarkable bifunctional electrocatalyst for boosting overall water splitting.

The development of a cost-effective and efficient bifunctional electrode for overall water splitting holds significant importance in accelerating the sustainable advancement of hydrogen energy. The present study involved a bifunctional catalytic electrode was prepared by loading NiCo-modified 1T/2H MoS2 onto carbonized wood (NiCo-MoS2-CW) using the hydrothermal and electrodeposition techniques. The XPS analysis revealed that NiCo-modified MoS2 exhibited a weak electron characteristic, which facilitated the ionization of H2O and significantly enhanced the Volmer step. The XPS analysis unveiled that NiCo-modified MoS2 displayed a weak electron characteristic, thereby promoting the ionization of H2O and substantially augmenting the Volmer step. The electrocatalytic performance of the NiCo-MoS2-CW in 1.0 M KOH is remarkably impressive, exhibiting minimal overpotentials of only 64 mV (10 mA cm-2) and 216 mV (50 mA cm-2) for the hydrogen evolution reaction and oxygen evolution reaction, respectively. The NiCo-MoS2-CW || NiCo-MoS2-CW electrolytic cell can achieve a cell voltage of only 1.69 V to achieve a current density of 50 mA cm-2. Overall, this study proposes a potential approach to improve the catalytic efficiency of overall water splitting by modulating the interfacial electronic properties of MoS2.

Molecular dynamics analysis of subsurface brittleness mechanism of nanocrystalline 3C-SiC rough friction surface.

To study the effect of polycrystalline 3C-SiC rough friction surface on the mechanism of subsurface brittleness during nanocrystalline grinding. Initial grinding models of polycrystalline 3C-SiC and diamond abrasive grains on rough friction surfaces are developed using molecular dynamics methods and the Voronoi method for constructing polycrystalline abrasive grains. The processing mechanism of 3C-SiC is analyzed by post-processing methods such as dislocation defect analysis, atomic arrangement analysis and stress analysis. At 2.6 nm, "stress concentration" occurs between the abrasive particles and the workpiece, forming irregular force shapes. The larger the grain size, the smaller the crystal hardness, the greater the possibility of crystal fracture, and it is obvious in the crystal of larger grains. At 8 nm, the crystal breaks and creates vacancies. The roughness of the polycrystalline 3C-SiC friction surface and the cross-cutting mechanism between grains with grain boundaries are found to be effective in ameliorating the damage in the subsurface layer.

A new extraction method of underglaze brown decorative pattern based on the coupling of single scale gamma correction and gray sharpening.

In order to solve the problem of image quality and morphological characteristics of primary underglaze brown decorative pattern extraction, this paper proposes a method of primary underglaze brown decorative pattern extraction based on the coupling of single scale gamma correction and gray sharpening. The single-scale gamma correction is combined with the gray sharpening method. The single-scale gamma correction improves the contrast and brightness of the image by nonlinear transformation, but may lead to the loss of image detail. Gray sharpening can enhance the high frequency component and improve the clarity of the image, but it will introduce noise. Combining these two technologies can compensate for their shortcomings. The experimental results show that this method can improve the efficiency of last element underglaze brown decorative pattern extraction by enhancing the image retention detail and reducing the influence of noise. The experimental results showed that F1Score, Miou(%), Recall, Precision and Accuracy(%) were 0.92745, 0.82253, 0.97942, 0.92458 and 0.92745, respectively.

CTHRC1 is associated with BRAF(V600E) mutation and correlates with prognosis, immune cell infiltration, and drug resistance in colon cancer, thyroid cancer, and melanoma.

Colon cancer, thyroid cancer, and melanoma are common malignant tumors that seriously threaten human health globally. The B-Raf proto-oncogene, serine/threonine kinase (BRAF)(V600E) mutation is an important driver gene mutation in these cancer types. In this study, we identified that collagen triple helix repeat containing 1 (CTHRC1) expression was associated with the BRAF(V600E) mutation in colon cancer, thyroid cancer, and melanoma. Based on database analysis and clinical tissue studies, CTHRC1 was verified to correlate with poor prognosis and worse clinicopathological features in colon cancer and thyroid cancer patients, but not in patients with melanoma. Several signaling pathways, immune cell infiltration, and immunotherapy markers were associated with CTHRC1 expression. Additionally, a high level of CTHRC1 was correlated with decreased sensitivity to antitumor drugs (vemurafenib, PLX-4720, dabrafenib, and SB-590885) targeting the BRAF(V600E) mutation. This study provides evidence of a significant correlation between CTHRC1 and the BRAF(V600E) mutation, suggesting its potential utility as a diagnostic and prognostic biomarker in human colon cancer, thyroid cancer, and melanoma.

Multiomics analysis of homologous recombination deficiency across cancer types.

There remains ongoing debate regarding the association of homologous recombination deficiency (HRD) with patient survival across various malignancies, highlighting the need for a comprehensive understanding of HRD's role in different cancer types. Based on data from databases, we conducted a multivariable omics analysis on HRD in 33 cancer types, focusing mainly on 23 cancers in which HRD was significantly associated with patient overall survival (OS) rates. This analysis included the mechanisms related to patient prognosis, gene expression, gene mutation, and signaling pathways. In this study, HRD was found to be significantly associated with patient prognosis, but its impact varied among different cancers. HRD was linked to different outcomes for patients with distinct tumor subtypes and was correlated with clinical features such as clinical stage and tumor grade. Driver gene mutations, including TP53, MUC4, KRAS, HRAS, FLG, ANK3, BRCA2, ATRX, FGFR3, NFE2L2, MAP3K1, PIK3CA, CIC, FUBP1, ALB, CTNNB1, and MED12, were associated with HRD across specific cancer types. We also analyzed differentially expressed genes (DEGs) and differentially methylated regions (DMRs) in relation to HRD levels in these cancers. Furthermore, we explored the correlation between HRD and signaling pathways, as well as immune cell infiltration. Overall, our findings contribute to a comprehensive understanding of HRD's multifaceted role in cancer.

Construction of a Colorimetric and Near-Infrared Ratiometric Fluorescent Sensor and Portable Sensing System for On-Site Quantitative Measurement of Sulfite in Food.

Sulfites play imperative roles in food crops and food products, serving as sulfur nutrients for food crops and as food additives in various foods. It is necessary to develop an effective method for the on-site quantification of sulfites in food samples. Here, 7-(diethylamino) quinoline is used as a fluorescent group and electron donor, alongside the pyridinium salt group as an electron acceptor and the C=C bond as the sulfite-specific recognition group. We present a novel fluorescent sensor based on a mechanism that modulates the efficiency of intramolecular charge transfer (ICT), CY, for on-site quantitative measurement of sulfite in food. The fluorescent sensor itself exhibited fluorescence in the near-infrared light (NIR) region, effectively minimizing the interference of background fluorescence in food samples. Upon exposure to sulfite, the sensor CY displayed a ratiometric fluorescence response (I447/I692) with a high sensitivity (LOD = 0.061 µM), enabling accurate quantitative measurements in complex food environments. Moreover, sensor CY also displayed a colorimetric response to sulfite, making sensor CY measure sulfite in both fluorescence and colorimetric dual-signal modes. Sensor CY has been utilized for quantitatively measuring sulfite in red wine and sugar with recoveries between 99.65% and 101.90%, and the RSD was below 4.0%. The sulfite concentrations in live cells and zebrafish were also monitored via fluorescence imaging. Moreover, the sulfite assimilated by lettuce leaves was monitored, and the results demonstrated that excessive sulfite in leaf tissue could lead to leaf tissue damage. In addition, the sulfate-transformed sulfite in lettuce stem tissue was tracked, providing valuable insights for evaluating sulfur nutrients in food crops. More importantly, to accomplish the on-site quantitative measurement of sulfite in food samples, a portable sensing system was prepared. Sensor CY and the portable sensing system were successfully used for the on-site quantitative measurement of sulfite in food.

Multiwalled Carbon Nanotubes-Reprogrammed Macrophages Facilitate Breast Cancer Metastasis via NBR2/TBX1 Axis.

In recent years, carbon nanotubes have emerged as a widely used nanomaterial, but their human exposure has become a significant concern. In our former study, we reported that pulmonary exposure of multiwalled carbon nanotubes (MWCNTs) promoted tumor metastasis of breast cancer; macrophages were key effectors of MWCNTs and contributed to the metastasis-promoting procedure in breast cancer, but the underlying molecular mechanisms remain to be explored. As a follow-up study, we herein demonstrated that MWCNT exposure in breast cancer cells and macrophage coculture systems promoted metastasis of breast cancer cells both in vitro and in vivo; macrophages were skewed into M2 polarization by MWCNT exposure. LncRNA NBR2 was screened out to be significantly decreased in MWCNTs-stimulated macrophages through RNA-seq; depletion of NBR2 led to the acquisition of M2 phenotypes in macrophages by activating multiple M2-related pathways. Specifically, NBR2 was found to positively regulate the downstream gene TBX1 through H3k27ac activation. TBX1 silence rescued NBR2-induced impairment of M2 polarization in IL-4 & IL-13-stimulated macrophages. Moreover, NBR2 overexpression mitigated the enhancing effects of MWCNT-exposed macrophages on breast cancer metastasis. This study uncovered the molecular mechanisms underlying breast cancer metastasis induced by MWCNT exposure.

Corrigendum: NUDT21 promotes tumor growth and metastasis through modulating SGPP2 in human gastric cancer.

[This corrects the article DOI: 10.3389/fonc.2021.670353.].

The signature of cuproptosis-related immune genes predicts the tumor microenvironment and prognosis of prostate adenocarcinoma.

Background: Cuproptosis plays a crucial role in cancer, and different subtypes of cuproptosis have different immune profiles in prostate adenocarcinoma (PRAD). This study aimed to investigate immune genes associated with cuproptosis and develop a risk model to predict prognostic characteristics and chemotherapy/immunotherapy responses of patients with PRAD. Methods: The CIBERSORT algorithm was used to evaluate the immune and stromal scores of patients with PRAD in The Cancer Genome Atlas (TCGA) cohort. Validation of differentially expressed genes DLAT and DLD in benign and malignant tissues by immunohistochemistry, and the immune-related genes of DLAT and DLD were further screened. Univariable Cox regression were performed to select key genes. Least absolute shrinkage and selection operator (LASSO)-Cox regression analyse was used to develop a risk model based on the selected genes. The model was validated in the TCGA, Memorial Sloan-Kettering Cancer Center (MSKCC) and Gene Expression Omnibus (GEO) datasets, as well as in this study unit cohort. The genes were examined via functional enrichment analysis, and the tumor immune features, tumor mutation features and copy number variations (CNVs) of patients with different risk scores were analysed. The response of patients to multiple chemotherapeutic/targeted drugs was assessed using the pRRophetic algorithm, and immunotherapy was inferred by the Tumor Immune Dysfunction and Exclusion (TIDE) and immunophenoscore (IPS). Results: Cuproptosis-related immune risk scores (CRIRSs) were developed based on PRLR, DES and LECT2. High CRIRSs indicated poor overall survival (OS), disease-free survival (DFS) in the TCGA-PRAD, MSKCC and GEO datasets and higher T stage and Gleason scores in TCGA-PRAD. Similarly, in the sample collected by the study unit, patients with high CRIRS had higher T-stage and Gleason scores. Additionally, higher CRIRSs were negatively correlated with the abundance of activated B cells, activated CD8+ T cells and other stromal or immune cells. The expression of some immune checkpoints was negatively correlated with CRIRSs. Tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH) and copy number variation (CNV) scores were all higher in the high-CRIRS group. Multiple chemotherapeutic/targeted drugs and immunotherapy had better responsiveness in the low-CRIRS group. Conclusion: Overall, lower CRIRS indicated better response to treatment strategies and better prognostic outcomes.

High-resolution mass spectrometry for glycoproteomics.

Tweetable abstract Bottom-up glycoproteomics combined with top-down strategy allows direct analysis of glycoform-mapped glycosylation and its glycans by high-resolution mass spectrometry.

Biosafe Bi2O2Se ultrathin nanosheet for water disinfection via solar-induced photothermal synergistic effect.

Solar-induced sterilization via photothermal synergy has attracted enormous attention due to its zero-energy consumption and the elimination of hazardous chemical disinfectant. Herein, we successfully synthesized a super biosafety Bi2O2Se with crossed nanosheet structure (Bi2O2Se-CN) for the sterilization of Escherichia coli (E. coli) via solar-induced photothermal synergistic effect. In comparison to bulk Bi2O2Se, the lower light reflection and more efficient photogenerated charge carrier separation under visible-infrared light irradiation resulted in the excellent sterilization effect of Bi2O2Se-CN, with a sterilization efficiency of 99.9% under the synergistic effect of light and heat. The crossed ultrathin nanosheet structure and suitable band gap width of Bi2O2Se-CN are fundamental reasons for its enhanced light absorption and charge carrier separation efficiency. Mechanistic studies showed that Bi2O2Se-CN can completely inactivate bacteria via generating a large amount of reactive oxygen species (•O2-, •OH, and 1O2) to attack the cell membrane, which further resulted in the reduced activity of intracellular enzymes and the leakage of intracellular contents. The biosafety property of Bi2O2Se-CN was confirmed by in vivo toxicological evaluation on the mice model. This work provided new ideas for the design of more efficient, energy-saving, biocompatible and environmental friendly solar water purification projects.

Thoracic Paravertebral Block Combined with General Anaesthesia or General Anaesthesia Alone for Thoracoscopic Lung Adenocarcinoma Surgery: A Retrospective Study.

Purpose: To investigate the effects of ultrasound-guided thoracic paravertebral block combined with general anaesthesia or general anaesthesia alone for thoracoscopic lung adenocarcinoma surgery, and to provide new thoughts for improving the clinical outcomes. Methods: This was a retrospective study. Data were retrieved for 195 patients with lung adenocarcinoma undergoing elective radical lobectomy via video-assisted thoracoscopy between January 2018 and August 2019 in The Second Hospital of Shandong University, including 86 patients who received thoracic paravertebral block (TPVB) combined with general anaesthesia (group TG), and 109 patients who received general anaesthesia alone (group GA). All patients were given self-controlled intravenous analgesia pump for 48 h after surgery. The primary outcome was the recurrence-free survival 2 years postoperatively (the time between surgery and the earliest date of recurrence, metastasis or lung cancer-cause death). The secondary outcomes included the average numeric rating scale (NRS) scores within 48 h postoperatively, the first time of postoperative ambulation, duration of chest tube drainage, length of postoperative hospitalization, perioperative opioid consumption and the postoperative side effects. Results: There were no statistical differences in the recurrence-free survival 2 years postoperatively between groups (Multivariate hazard ratio 0.706, 95% CI 0.126-3.941, P=0.691). The average NRS scores within 48 h postoperatively were significantly lower in group TG (P<0.05). The first time of postoperative ambulation, duration of chest tube drainage, and length of postoperative hospitalization in group TG were significantly reduced (P<0.05). Opioid consumption was significantly decreased in group TG (P<0.01). Finally, the incidence of postoperative nausea and vomiting (PONV) was significantly lower in group TG (P<0.05). Conclusion: TPVB for thoracoscopic lung adenocarcinoma surgery did not improve the recurrence-free survival 2 years postoperatively compared with general anaesthesia alone, but it significantly enhanced the postoperative analgesia effect, reduced opioid consumption as well as side effects, and accelerated postoperative early recovery. Clinical Trial Registration Number: The Chinese Clinical Trial Registry (ChiCTR-2100050454).

mPGES-2 blockade antagonizes ß-cell senescence to ameliorate diabetes by acting on NR4A1.

ß-cell dysfunction is a hallmark of type 1 and type 2 diabetes. Type 2 diabetes is strongly associated with ageing-related ß-cell abnormalities that arise through unknown mechanisms. Here we show better ß-cell identity, less ß-cell senescence, enhanced glucose-stimulated insulin secretion and improved glucose homeostasis in global microsomal prostaglandin E synthase-2 (mPGES-2)-deficient mice challenged with a high-fat diet or bred with a genetic model of type 2 diabetes (db/db mice). Furthermore, the function of mPGES-2 in ß-cells is validated using mice with ß-cell-specific mPGES-2 deficiency or overexpression. Mechanistically, the protective role of mPGES-2 deletion is induced by antagonizing ß-cell senescence via interference of the PGE2-EP3-NR4A1 signalling axis. We also discover an inhibitor of mPGES-2, SZ0232, which protects against ß-cell dysfunction and diabetes, similar to mPGES-2 deletion. We conclude that mPGES-2 contributes to ageing-associated ß-cell senescence and dysfunction via the PGE2-EP3-NR4A1 signalling axis. Pharmacologic blockade of mPGES-2 might be effective for treating ageing-associated ß-cell dysfunction and diabetes.

A Novel Small Molecular Antibody, HER2-Nanobody, Inhibits Tumor Proliferation in HER2-Positive Breast Cancer Cells In Vitro and In Vivo.

Breast cancer is the most common malignant cancer in women worldwide, especially in developing countries. Herceptin is a monoclonal antibody with an antitumor effect in HER2-positive breast cancer. However, the large molecular weight of Herceptin limited its employment. In this study, we constructed and screened HER2-nanobody and verified its tumor-suppressive effect in HER2-positive breast cancer cells. HER2-nanobody was established, filtrated, purified, and was demonstrated to inhibit cell total number, viability, colony formation and mitosis, and promote cell apoptosis in HER2-positive breast cancer cells in vitro. Treated with HER2-nanobody, tumor growth was significantly inhibited by both intratumor injection and tail intravenous injection in vivo. The phosphorylation of ERK and AKT was restrained by HER2-nanobody in HER2-positive breast cancer cells. RAS-RAF-MAPK and PI3K-AKT-mTOR are two important pathways involved in HER2. It was credible for HER2-nanobody to play the tumor suppressive role by inhibiting the phosphorylation of ERK and AKT. Therefore, HER2-nanobody could be employed as a small molecular antibody to suppress HER2-positive breast cancer.