TSPAN8+ myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer.

Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, the heterogeneity and regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry analysis and identified a distinct senescence-like tetraspanin-8 (TSPAN8)+ myofibroblastic CAF (myCAF) subset, which is correlated with therapeutic resistance and poor survival in multiple cohorts of patients with breast cancer (BC). TSPAN8+ myCAFs potentiate the stemness of the surrounding BC cells through secretion of senescence-associated secretory phenotype (SASP)-related factors IL-6 and IL-8 to counteract chemotherapy. NAD-dependent protein deacetylase sirtuin 6 (SIRT6) reduction was responsible for the senescence-like phenotype and tumor-promoting role of TSPAN8+ myCAFs. Mechanistically, TSPAN8 promoted the phosphorylation of ubiquitin E3 ligase retinoblastoma binding protein 6 (RBBP6) at Ser772 by recruiting MAPK11, thereby inducing SIRT6 protein destruction. In turn, SIRT6 down-regulation up-regulated GLS1 and PYCR1, which caused TSPAN8+ myCAFs to secrete aspartate and proline, and therefore proved a nutritional niche to support BC outgrowth. By demonstrating that TSPAN8+SIRT6low myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8+ myCAFs is a promising approach to circumvent chemoresistance.

P2X7 receptors: a bibliometric review from 2002 to 2023.

For many years, there has been ongoing research on the P2X7 receptor (P2X7R). A comprehensive, systematic, and objective evaluation of the scientific output and status of P2X7R will be instrumental in guiding future research directions. This study aims to present the status and trends of P2X7R research from 2002 to 2023. Publications related to P2X7R were retrieved from the Web of Science Core Collection database. Quantitative analysis and visualization tools were Microsoft Excel, VOSviewer, and CiteSpace software. The analysis content included publication trends, literature co-citation, and keywords. 3282 records were included in total, with the majority of papers published within the last 10 years. Based on literature co-citation and keyword analysis, neuroinflammation, neuropathic pain, gastrointestinal diseases, tumor microenvironment, rheumatoid arthritis, age-related macular degeneration, and P2X7R antagonists were considered to be the hotspots and frontiers of P2X7R research. Researchers will get a more intuitive understanding of the status and trends of P2X7R research from this study.

Bilateral thalamic and brainstem anaplastic astrocytoma: A case report.

RATIONALE: Bilateral thalamic glioma is extremely rare and characterized by strictly limited involvement of bilateral thalami. To investigate its clinical and neuroimaging features, we herein reported a rare case of anaplastic astrocytoma (AA) involving both thalami and the brainstem and reviewed the literature. PATIENT CONCERNS: A-33-year-old Chinese woman was referred to our department owing to persistent headache and nausea and vomiting. Neurological examination showed mild cognitive impairment and positive Kernig sign. DIAGNOSIS: Brain magnetic resonance imaging (MRI) demonstrated asymmetrical and swollen lesions involving both thalami, midbrain and pontine tegmentum, without restricted diffusion or enhancement. On day 7 after admission, she was transferred to the department of neurosurgery and underwent a stereotactic brain biopsy of the right thalamic lesion. Histopathological features and immunohistochemistry were consistent with AA, IDH wild-type, World Health Organization grade III. INTERVENTIONS: She was administrated with mannitol and glycerin fructose for decreasing intracranial pressure. OUTCOMES: In spite of receiving chemotherapy, she died on 2-month after her initial diagnosis. LESSONS: AA involving in both thalami and brainstem is a rare entity with poor prognosis. The clinicians and radiologists should deepen their awareness of the specific MRI feature of bilateral thalamic involvement. When MRI alone is insufficient, the utility of stereotactic biopsy is essential for making a definitive diagnosis.

Entity relationship extraction from Chinese electronic medical records based on feature augmentation and cascade binary tagging framework.

Extracting entity relations from unstructured Chinese electronic medical records is an important task in medical information extraction. However, Chinese electronic medical records mostly have document-level volumes, and existing models are either unable to handle long text sequences or exhibit poor performance. This paper proposes a neural network based on feature augmentation and cascade binary tagging framework. First, we utilize a pre-trained model to tokenize the original text and obtain word embedding vectors. Second, the word vectors are fed into the feature augmentation network and fused with the original features and position features. Finally, the cascade binary tagging decoder generates the results. In the current work, we built a Chinese document-level electronic medical record dataset named VSCMeD, which contains 595 real electronic medical records from vascular surgery patients. The experimental results show that the model achieves a precision of 87.82% and recall of 88.47%. It is also verified on another Chinese medical dataset CMeIE-V2 that the model achieves a precision of 54.51% and recall of 48.63%.

Single-cell RNA sequencing reveals the immunoregulatory roles of PegIFN-α in patients with chronic hepatitis B.

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) is caused by HBV infection and affects the lives of millions of people worldwide by causing liver inflammation, cirrhosis, and liver cancer. Interferon-alpha (IFN-α) therapy is a conventional immunotherapy that has been widely used in CHB treatment and achieved promising therapeutic outcomes by activating viral sensors and interferon-stimulated genes (ISGs) suppressed by HBV. However, the longitudinal landscape of immune cells of CHB patients and the effect of IFN-α on the immune system are not fully understood. APPROACH AND RESULTS: Here, we applied single-cell RNA sequencing (scRNA-seq) to delineate the transcriptomic landscape of peripheral immune cells in CHB patients before and after PegIFN-α therapy. Notably, we identified three CHB-specific cell subsets, pro-inflammatory (Pro-infla) CD14+ monocytes, Pro-infla CD16+ monocytes and IFNG+ CX3CR1- NK cells, which highly expressed proinflammatory genes and positively correlated with HBsAg. Furthermore, PegIFN-α treatment attenuated percentages of hyperactivated monocytes, increased ratios of long-lived naive/memory T cells and enhanced effector T cell cytotoxicity. Finally, PegIFN-α treatment switched the transcriptional profiles of entire immune cells from TNF-driven to IFN-α-driven pattern and enhanced innate antiviral response, including virus sensing and antigen presentation. CONCLUSIONS: Collectively, our study expands the understanding of the pathological characteristics of CHB and the immunoregulatory roles of PegIFN-α, which provides a new powerful reference for the clinical diagnosis and treatment of CHB.

MLLT11 siRNA Inhibits the Migration and Promotes the Apoptosis of MDA-MB-231 Breast Cancer Cells.

Breast cancer is considered the most prevalent malignancy due to its high incidence rate, recurrence, and metastasis in women that makes it one of the deadliest cancers. The current study aimed to predict the genes associated with the recurrence and metastasis of breast cancer and to validate their effect on MDA-MB-231 cells. Through the bioinformatics analysis, the transcription factor 7 cofactor (MLLT11) as the target gene was obtained. MLLT11-specific siRNA was synthesized and transfected into MDA-MB-231 cells. The results demonstrated that the siRNA significantly reduced the MLLT11 mRNA levels. Moreover, cell migration and invasion, as well as the protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, matrix metalloproteinase (MMP) 2, and MMP9, were significantly lower in the groups treated with siRNA while the apoptosis was augmented. Collectively, MLLT11 siRNA elicited ameliorative properties on breast cancer cells, possibly via the inhibition of the PI3K/AKT signaling pathway.

siRNA-based approaches for castration-resistant prostate cancer therapy targeting the androgen receptor signaling pathway.

Androgen deprivation therapy is a common treatment method for metastatic prostate cancer through lowering androgen levels; however, this therapy frequently leads to the development of castration-resistant prostate cancer (CRPC). This is attributed to the activation of the androgen receptor (AR) signaling pathway. Current treatments targeting AR are often ineffective mostly due to AR gene overexpression and mutations, as well as the presence of splice variants that accelerate CRPC progression. Thus there is a critical need for more specific medication to treat CRPC. Small interfering RNAs have shown great potential as a targeted therapy. This review discusses prostate cancer progression and the role of AR signaling in CRPC, and proposes siRNA-based targeted therapy as a promising strategy for CRPC.

Tumor-associated macrophages confer colorectal cancer 5-fluorouracil resistance by promoting MRP1 membrane translocation via an intercellular CXCL17/CXCL22-CCR4-ATF6-GRP78 axis.

Chemotherapy represents a major type of clinical treatment against colorectal cancer (CRC). Aberrant drug efflux mediated by transporters acts as a key approach for tumor cells to acquire chemotherapy resistance. Increasing evidence implies that tumor-associated macrophages (TAMs) play a pivotal role in both tumorigenesis and drug resistance. Nevertheless, the specific mechanism through which TAMs regulate drug efflux remains elusive. Here, we discovered that TAMs endow CRC cells with resistance to 5-fluorouracil (5-FU) treatment via a cell-cell interaction-mediated MRP1-dependent drug efflux process. Mechanistically, TAM-secreted C-C motif chemokine ligand 17 (CCL17) and CCL22, via membrane receptor CCR4, activated the PI3K/AKT pathway in CRC tumor cells. Specifically, phosphorylation of AKT inactivated IP3R and induced calcium aggregation in the ER, resulting in the activation of ATF6 and upregulation of GRP78. Accordingly, excessive GRP78 can interact with MRP1 and promote its translocation to the cell membrane, causing TAM-induced 5-FU efflux. Taken together, our results demonstrated that TAMs promote CRC chemotherapy resistance via elevating the expression of GRP78 to promote the membrane translocation of MRP1 and drug efflux, providing direct proof for TAM-induced drug resistance.

Correction: The Genetic Landscape of Ocular Adnexa MALT Lymphoma Reveals Frequent Aberrations in NFAT and MEF2B Signaling Pathways.

[This corrects the article DOI: 10.1158/2767-9764.CRC-21-0022.][This corrects the article DOI: 10.1158/2767-9764.CRC-21-0022.].

NDRG3 regulates imatinib resistance by promoting ß­catenin accumulation in the nucleus in chronic myelogenous leukemia.

Imatinib resistance in chronic myelogenous leukemia (CML) is a clinical problem. The present study examined the role of N­Myc downstream regulatory gene 3 (NDRG3) in imatinib resistance in CML. Quantitative PCR demonstrated that NDRG3 was highly expressed in patients with CML. Cell Counting Kit (CCK)­8 experiments proved that NDRG3 promoted the proliferation of K562 CML cells and enhanced imatinib resistance. Dual­luciferase assay showed that microRNA (miR)­204­5p inhibited expression of NDRG3 and immunofluorescence experiments showed that NDRG3 promoted accumulation of ß­catenin in the nucleus, thereby increasing the expression of downstream drug resistance­ and cell cycle­associated factors (c­Myc and MDR1). At the same time, cell proliferation experiments showed that ß­catenin played a role in cell proliferation and drug resistance. Co­transfection with small interfering (si)­ß­catenin partially reversed the effect of NDRG3. This finding indicated that NDRG3 plays an important role in imatinib resistance and miR­204­5p and ß­catenin are involved in the biological behavior of NDRG3. The present results provide theoretical support for overcoming drug resistance in CML.

DMBT1 Alleviates Nasal Airway Inflammatory Response in the LPS-Induced Nasal Polyp Model.

INTRODUCTION: The aim of this study was to investigate the effects and mechanism of deleted in malignant brain tumors 1 (DMBT1) protein on the mouse model of nasal polyps. METHODS: The mouse model of nasal polyps was induced by intranasal drip intervention of lipopolysaccharide (LPS) 3 times a week for 12 weeks. A total of 42 mice were randomly divided into blank group, LPS group, and LPS+DMBT1 group. DMBT1 protein was applied by intranasal drip intervention in each nostril after LPS. After 12 weeks, 5 mice in each group were randomly picked for the mouse olfactory disorder experiment, 3 mice were randomly picked for histopathological observation of nasal mucosa, 3 mice for olfactory marker protein (OMP) immunofluorescence analysis and the last 3 mice were grabbed for nasal lavage, and the levels of cytokines interleukin (IL)-4, IL-5, IL-13, and phosphatidylinositide 3-kinases (PI3K) in the nasal lavage fluid were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the blank group, mice in LPS group had olfactory dysfunction, the level of OMP was significantly reduced, the nasal mucosa was swollen, discontinuous, and contained a large number of inflammatory cells. The levels of IL-4, IL-5, IL-13, and PI3K in the nasal lavage fluid were significantly increased in LPS group (p < 0.01). Compared with the LPS group, the number of mice with olfactory dysfunction in the LPS+DMBT1 group was less, the infiltration of inflammatory cells was reduced, the OMP-positive cells were significantly increased, and the IL-4, IL-5, IL-13, and PI3K in the nasal lavage fluid were significantly increased, p < 0.01. CONCLUSIONS: DMBT1 protein alleviates the nasal airway inflammatory response in the mouse nasal polyp model, and the mechanism may be through the PI3K-AKT signaling pathway.

Effects of Shale Pore Size and Connectivity on scCO2 Enhanced Oil Recovery: A Molecular Dynamics Simulation Investigation.

The differences in pore width distributions and connectivity of shale reservoirs have significant influences on supercritical carbon dioxide (scCO2)-enhanced oil recovery (CO2 EOR) in shale. Herein, the molecular dynamics simulation was adopted to investigate the microscopic mechanism of CO2 EOR in the shale nanopores with different pore size width distributions and pore connectivity. The results show that the pore connectivity has significant effects on the oil displacement, and the recovery efficiency is ordered as: connected pore > double pore > single pore for the 3 nm pore, which are 91.32, 74.43, and 65.93%, respectively. Therefore, the increase in pore connectivity can significantly improve the recovery efficiency of the small pore of the connected pore system. For the shale reservoirs with different pore width distributions, the oil recovery rate of large pores is generally higher than that of small pores. In addition, the displacement of oil in the small pore of the double pore system is accelerated due to the pushing effect of the discharge fluid from the large pore. The results furnish a certain theoretical support for the research of the microscopic mechanism of CO2 EOR in the shale pore with different pore width distributions and connectivity and the exploit of shale oil.

WSP from "Nostoc commune" Vauch. suppresses gastric cancer migration via EGFRVIII signaling.

Introduction: A number of evidences have proved that "Nostoc commune" Vauch can improve human immunity and prevent diseases, however, the specific mechanism remains unclear. The biological activity of the main protein component of "Nostoc commune" Vauch extracellular matrix- a water-stress protein (WSP) still needs to be elucidated. Methods: In our study, we validated the role of WSP in gastric cancer metastasis at the cellular level, the organoid level and in mouse models, and also studied the role of EGFRVIII and downstream signaling molecules after WSP treatment. Results: We found that WSP can significantly inhibit the metastasis of gastric cancer cells. Interestingly, we found that the anti-metastasis ability of WSP on gastric cancer was related to membrane protein receptor EGFRVIII, which was realized by inhibiting the downstream EGFRVIII signaling pathway. In terms of mechanism, WSP can inhibit the downstream EGFRVIII signaling pathway Akt-PI3K and further inhibit the secretion of cancer-related metastasis proteins such as MMP2 and MMP9, thus, significantly affecting the metastasis of gastric cancer cells. Discussion: Given the anticancer properties of WSP, drug developers and manufacturers can further develop protein drugs for cancer patients using protein engineering techniques based on the properties of WSP.

Vitamin D Receptor Gene Polymorphisms and the Risk of CIN2+ in Shanxi Population.

Cervical cancer is one of the most common malignancies in women with high morbidity and mortality. Human papillomavirus (HPV) infection is the primary cause of cervical cancer, of which HPV 16 is the predominant. Early detection and effective treatment of cervical precancerous lesions are the key to preventing cervical cancer. Vitamin D receptor (VDR) gene polymorphism is considered to be an important cause of cancer development. Here, we studied the association of VDR polymorphisms (FOKI, BsmI, ApaI, and TaqI) in HPV16-positive cervical intraepithelial neoplasia (CIN)2+ patients. HPV16-positive patients who visited the Colposcopy Clinic of Obstetrics and Gynecology, the Second Hospital of Shanxi Medical University for biopsy due to abnormal HPV and/or Thinprep cytologic test (TCT) from September 1, 2020 to October 1, 2021 were grouped by pathological results. The fasting blood samples were collected and VDR polymorphisms were detected using TaqMan fluorescent probes, and the three sites of BsmI-ApaI-TaqI were subjected to haplotype analysis. FOKI ff genotype (OR = 2.01; 95% CI = 1.12 - 3.59; p = 0.019) and f allele (OR = 1.48; 95% CI = 1.10 - 1.98; p = 0.009) were found to be associated with the risk of CIN2+. TaqI Tt genotype (OR = 2.03; 95% CI = 1.20 - 3.43; p = 0.008), tt genotype (OR = 2.09; 95% CI = 1.09 - 4.02; p = 0.028), and t allele (OR = 1.35; 95% CI = 1.01 - 1.80; p = 0.041) were associated with the risk of CIN2+. No haplotype was associated with CIN2+ risk. According to the results, FOKI and TaqI polymorphisms are associated with CIN2+ risk.

Multidisciplinary Progress in Obesity Research.

Obesity is a chronic disease that endangers human health. In recent years, the phenomenon of obesity has become more and more common, and it has become a global epidemic. Obesity is closely associated with many adverse metabolic changes and diseases, such as insulin resistance, type 2 diabetes mellitus, coronary heart disease, nervous system diseases and some malignant tumors, which have caused a huge burden on the country's medical finance. In most countries of the world, the incidence of cancer caused by obesity is increasing year on year. Diabetes associated with obesity can lead to secondary neuropathy. How to treat obesity and its secondary diseases has become an urgent problem for patients, doctors and society. This article will summarize the multidisciplinary research on obesity and its complications.

Potential utility of miRNAs for liquid biopsy in breast cancer.

Breast cancer (BC) remains the most prevalent malignancy due to its incidence rate, recurrence, and metastasis in women. Conventional strategies of cancer detection- mammography and tissue biopsy lack the capacity to detect the complete cancer genomic landscape. Besides, they often give false- positive or negative results. The presence of this and other disadvantages such as invasiveness, high-cost, and side effects necessitates developing new strategies to overcome the BC burden. Liquid biopsy (LB) has been brought to the fore owing to its early detection, screening, prognosis, simplicity of the technique, and efficient monitoring. Remarkably, microRNAs (miRNAs)- gene expression regulators seem to play a major role as biomarkers detected in the samples of LB. Particularly, miR-21 and miR-155 among other possible candidates seem to serve as favorable biomarkers in the diagnosis and prognosis of BC. Hence, this review will assess the potential utility of miRNAs as biomarkers and will highlight certain promising candidates for the LB approach in the diagnosis and management of BC that may optimize the patient outcome.

[Balloon dilation with stent implantation for the treatment of Eustachian tube obstruction].

When the Eustachian tube is dysfunctional, the external air cannot enter the middle ear, resulting in a negative pressure state in the middle ear, which can cause a series of pathological changes in the middle ear. In this paper, 13 patients with recurrence of otitis media after balloon dilatation of the Eustachian tube were treated with stenting in the Eustachian tube for Eustachian tube dysfunction with satisfactory results, and this method can provide a reference for the clinical treatment of Eustachian tube dysfunction.

Pegylated interferon-α-2b combined with tenofovir disoproxil fumarate, granulocyte-macrophage colony-stimulating factor, and hepatitis B vaccine treatment for naïve HBeAg-positive chronic hepatitis B patients: A prospective, multicenter, randomized controlled study.

Hepatitis B surface antigen (HBsAg) loss or seroconversion is an ideal treatment endpoint for patients with chronic hepatitis B but is rarely achievable in  hepatitis B e-antigen (HBeAg)-positive patients using existing treatment strategies. In this study, the effect of pegylated interferon (peg-IFN) alfa-2b plus tenofovir disoproxil fumarate (TDF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and hepatitis B vaccine was evaluated. This randomized controlled trial was conducted at nine liver centers in Chinese university hospitals from May 2018 to July 2020. Patients (n = 303) enrolled were randomly administered peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine (experimental group); peg-IFN-α-2b plus TDF (control group 2); or interferon-α-2b alone (control group 1). The primary efficacy endpoint was HBsAg seroconversion at 48 weeks and the secondary endpoint included safety. No differences in baseline HBsAg levels were observed among the groups. The primary endpoint was achieved in three (3.0%), one (1.03%), and one (1.19%) patient in the experimental group, control group 2, and control group 1, respectively. The incidence of HBsAg seroconversion at week 48 was not significantly different among the three groups (p = 0.629). However, the decrease in serum levels of HBsAg at week 48 was significantly higher in the experimental and control group 2 compared with that in control group 1 (p = 0.008 and 0.006, respectively). No significant difference between the experimental and control group 2 was observed (p = 0.619). Adverse events were not significantly different among the groups except for the lower incidence of neutropenia in the experimental group. Peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine is not superior to peg-IFN-α-2b combined with TDF in HBeAg-positive naïve patients. Clinical Trials Registration: ChiCTR1800016173.

EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription.

TSPAN family of proteins are generally considered to assemble as multimeric complexes on the plasma membrane. Our previous work uncovered that TSPAN8 can translocate into the nucleus as a membrane-free form, a process that requires TSPAN8 palmitoylation and association with cholesterol to promote its extraction from the plasma membrane and subsequent binding with 14-3-3θ and importin-ß. However, what upstream signal(s) regulate(s) the nuclear translocation of TSPAN8, the potential function of TSPAN8 in the nucleus, and the underlying molecular mechanisms all remain unclear. Here, we demonstrate that, epidermal growth factor receptor (EGFR) signaling induces TSPAN8 nuclear translocation by activating the kinase AKT, which in turn directly phosphorylates TSPAN8 at Ser129, an event essential for its binding with 14-3-3θ and importin ß1. In the nucleus, phosphorylated TSPAN8 interacts with STAT3 to enhance its chromatin occupancy and therefore regulates transcription of downstream cancer-promoting genes, such as MYC, BCL2, MMP9, etc. The EGFR-AKT-TSPAN8-STAT3 axis was found to be hyperactivated in multiple human cancers, and associated with aggressive phenotype and dismal prognosis. We further developed a humanized monoclonal antibody hT8Ab4 that specifically recognizes the large extracellular loop of TSPAN8 (TSPAN8-LEL), thus being able to block the extraction of TSPAN8 from the plasma membrane and consequently its nuclear localization. Importantly, both in vitro and in vivo studies demonstrated an antitumor effect of hT8Ab4. Collectively, we discovered an unconventional function of TSPAN8 and dissected the underlying molecular mechanisms, which not only showcase a new layer of biological complexity of traditional membrane proteins, but also shed light on TSPAN8 as a novel therapeutic target for refractory cancers.

Pd-Fe3O4 Janus nanozyme with rational design for ultrasensitive colorimetric detection of biothiols.

Although nanozyme-based colorimetric assays have been broadly used for biosensing, some limitations such as low catalytic activity of nanozyme, poor sensitivity to analytes and lack of understanding the structure-activity relationship remain unsolved. In this work, we developed an ultrasensitive colorimetric method for biothiols detection based on density functional theory-assisted design of janus Pd-Fe3O4 nanozyme. The Pd-Fe3O4 dumbbell-like nanoparticles (DBNPs) prepared by seed-mediated approach shows a uniform heterodimeric nanostructure. Ultrasensitive biothiols detection is achieved from two aspects. On one hand, due to the synergistic effect between Pd and Fe3O4 in the dumbbell structure, Pd-Fe3O4 DBNPs show enhanced peroxidase-mimic activity compared to the individual components. On the other hand, when the target biothiols molecule is present, its inhibition effect on the janus Pd-Fe3O4 nanozyme is also significantly enhanced. The above results are confirmed both in experiment and theoretical calculation. Based on the rational design, a simple, highly selective and urtrasensitive colorimetric and quantitative assay for biothiols is developed. The limit of detection (LOD) can reach as low as 3.1 nM in aqueous solution. This assay is also successfully applied to the detection of biothiols in real urine samples. Moreover, the Pd-Fe3O4 nanozyme is used to discriminate biothiols levels in normal and cancer cells with high sensitivity at the cell density of 15,000/mL, which demonstrates its great potential in biological and clinical analysis. This work not only shows the great promise of janus bimetallic nanozymes' excellent functionalities but also provides rational guidelines to design high-performance nanozymes for biosensing and biomedical applications.