A Poly(amino acid)-Based Nanomedicine Strategy: Telomere-Telomerase Axis Targeting and Magnetic Resonance Imaging in Hepatocellular Carcinoma Treatment.

Targeting telomere maintenance has emerged as a promising strategy for hepatocellular carcinoma (HCC) treatment. However, given the duality of the telomere-telomerase axis in telomere maintenance, a comprehensive strategy is urgently needed. Herein, we develop a poly(amino acid) (D-PAAs)-based strategy for spatiotemporal codelivery of telomerase inhibitor, BIBR1523, and AKT inhibitor, isobavachalcone. By leveraging D-PAAs' modifiability, we synthesize polymer-inhibitor conjugates (PB and PI) and a folic acid-decorated tumor-targeting vector (PF). These building blocks undergo micellization to fabricate a codelivery nanomedicine (P-BI@P-FA) by exploiting D-PAAs' noncovalent assembly. P-BI@P-FA improves the pharmacokinetics, tumor selectivity, and bioavailability of small molecule inhibitors and initiates a dual telomere-specific inhibition by combining telomerase deactivation with telomere disruption. Furthermore, a hybrid tumor-targeting magnetic nanosystem is designed using D-PAAs and manganese dioxide to showcase magnetic resonance imaging capacities. Our D-PAAs-based strategy addresses the pressing need for telomere-specific HCC treatment while allowing for diagnostic application, presenting a promising avenue for nanomedicine design.

Sodium thiosulfate: A donor or carrier signaling molecule for hydrogen sulfide?

Sodium thiosulfate has been used for decades in the treatment of calciphylaxis and cyanide detoxification, and has recently shown initial therapeutic promise in critical diseases such as neuronal ischemia, diabetes mellitus, heart failure and acute lung injury. However, the precise mechanism of sodium thiosulfate remains incompletely defined and sometimes contradictory. Although sodium thiosulfate has been widely accepted as a donor of hydrogen sulfide (H2S), emerging findings suggest that it is the executive signaling molecule for H2S and that its effects may not be dependent on H2S. This article presents an overview of the current understanding of sodium thiosulfate, including its synthesis, biological characteristics, and clinical applications of sodium thiosulfate, as well as the underlying mechanisms in vivo. We also discussed the interplay of sodium thiosulfate and H2S. Our review highlights sodium thiosulfate as a key player in sulfide signaling with the broad clinical potential for the future.

Temporal dynamics of the microbial heterogeneity-diversity relationship in microcosmic systems.

Spatial heterogeneity significantly enhances biodiversity, representing one of the ecology's most enduring paradigms. However, many studies have found decreasing, humped, and neutral correlations between spatial heterogeneity and biodiversity (heterogeneity-diversity relationships, HDR). These findings have pushed this widely accepted theory back into controversy. Microbial HDR research has lagged compared to that of plants and animals. Nevertheless, microbes have features that add a temporal-scale perspective to HDR research that is critical to understanding patterns of HDR. In this study, 157 microcosms with different types spatial heterogeneity were set up to map the HDR of microorganisms and their temporal dynamics using high-throughput sequencing techniques. The results show that the following: 1. Spatial heterogeneity can significantly alter microbial diversity in microcosmic systems. Changes in microbial diversity, in turn, lead to changes in environmental conditions. These changes caused microorganisms to exhibit increasing, decreasing, humped, U-shaped, and neutral HDR patterns. 2. The emergence of HDR patterns is characterized by temporal dynamics. Additionally, the HDR patterns generated by spatial structural and compositional heterogeneity exhibit inconsistent emergence times. These results suggest that the temporal dynamics of HDR may be one of the reasons for the coexistence of multiple patterns in previous studies. The feedback regulation between spatial heterogeneity-biodiversity-environmental conditions is an essential reason for the temporally dynamics of HDR patterns. All future ecological studies should pay attention to the temporal dynamic patterns of ecological factors.

Secondary metabolites from the fungus Cladosporium xylophilum.

A new cladosporol derivative xylophilum A (1), together with 10 known compounds (2-11), were isolated from the rice fermentation of the fungus Cladosporium xylophilum. Their structures were established by extensive spectroscopic methods and comparison of their NMR data with literatures. The antimicrobial activity of compound 1 against 11 kinds of pathogenic microbial was evaluated, but no significant activity was found (MIC >100 µg/ml).

Current Lifetime of Single-Nanoparticle Electrochemical Collision for In Situ Monitoring Nanoparticles Agglomeration and Aggregation.

In situ monitoring of the agglomeration/aggregation process of nanoparticles (NPs) is crucial because it seriously affects cell entry, biosafety, catalytic performance of NPs, and so on. Nevertheless, it remains hard to monitor the solution phase agglomeration/aggregation of NPs via conventional techniques such as electron microscopy, which requires sample pretreatment and cannot represent native state NPs in solution. Considering that single-nanoparticle electrochemical collision (SNEC) is powerful to detect NPs in solution at the single-particle level, and the current lifetime, which refers to the time that current intensity decays to 1/e of the original value, is skilled in distinguishing different sized NPs, herein, a current lifetime-based SNEC has been developed to distinguish a single Au NP (d = 18 nm) from its agglomeration/aggregation. Based on this, the agglomeration/aggregation process of small-sized NPs and the discrimination of agglomeration vs aggregation have been carefully investigated at the single-particle level. Results showed that the agglomeration/aggregation of Au NPs (d = 18 nm) in 0.8 mM HClO4 climbed from 19% to 69% over two hours, whereas there was no visible granular sediment, and Au NPs tended to agglomerate rather than aggregate irreversibly under normal conditions. Hence, the proposed current lifetime-based SNEC could serve as a complementary method to in situ monitor the agglomeration/aggregation of small-sized NPs in solution at the single-particle level and provide effective guidance for the practical application of NPs.

Clinical and electrocardiographic features in acute total left main coronary artery occlusion without collateral circulation.

BACKGROUNDS: Study concerning the clinical features, electrocardiogram (ECG) findings and outcomes in patients presenting with acute total occlusion of left main coronary artery (LM) without collateral circulation is limited. METHODS: 25 patients with acute total LM occlusion without collateral circulation by emergency coronary angiography, from muti-center registry, were retrospectively studied. The clinical and angiographic characteristics, ECG and in-hospital mortality were reviewed. RESULTS: Nineteen patients (76%) presented with cardiogenic shock. Twelve (60%, 12/20) patients had coronary slow flow or no reflow phenomenon after primary percutaneous coronary intervention (PCI). The in-hospital mortality rate was 88% (n = 22). All the patients presented with ST-segment elevation myocardial ischemia (STEMI) pattern, mostly involving leads I, aVL, V2, V3, V4, V5 and ST-segment depression in leads II, III and aVF. CONCLUSIONS: Acute total LM occlusion without collateral circulation portends high in-hospital mortality. Anterior ST elevation in the precordial leads from V2 to V4 through V6, and ST elevation in leads I and aVL, accompanying with ST depression in the inferior leads is associated with acute total LM occlusion without collateral circulation.

A new chamigrane sesquiterpene from the basidiomycete Antrodiella albocinnamomea.

One new chamigrane sesquiterpene, antroalbol A (1), was isolated from the cultures of the higher fungus Antrodiella albocinnamomea. Its structure was established by means of spectroscopic methods, and the absolute configuration of 1 was confirmed by single crystal x-ray diffraction analysis. The compound was evaluated for its cytotoxicity against five human cancer cell lines, but no significant cytotoxicity was found.

Recent Advances in Well-Designed Therapeutic Nanosystems for the Pancreatic Ductal Adenocarcinoma Treatment Dilemma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with an extremely poor prognosis and low survival rate. Due to its inconspicuous symptoms, PDAC is difficult to diagnose early. Most patients are diagnosed in the middle and late stages, losing the opportunity for surgery. Chemotherapy is the main treatment in clinical practice and improves the survival of patients to some extent. However, the improved prognosis is associated with higher side effects, and the overall prognosis is far from satisfactory. In addition to resistance to chemotherapy, PDAC is significantly resistant to targeted therapy and immunotherapy. The failure of multiple treatment modalities indicates great dilemmas in treating PDAC, including high molecular heterogeneity, high drug resistance, an immunosuppressive microenvironment, and a dense matrix. Nanomedicine shows great potential to overcome the therapeutic barriers of PDAC. Through the careful design and rational modification of nanomaterials, multifunctional intelligent nanosystems can be obtained. These nanosystems can adapt to the environment's needs and compensate for conventional treatments' shortcomings. This review is focused on recent advances in the use of well-designed nanosystems in different therapeutic modalities to overcome the PDAC treatment dilemma, including a variety of novel therapeutic modalities. Finally, these nanosystems' bottlenecks in treating PDAC and the prospect of future clinical translation are briefly discussed.

[A cohort study of vincristine-induced peripheral neuropathy in children]. / é•¿æ˜¥æ–°ç¢±è¯±å¯¼çš„å‘¨å›´ç¥žç»ç— å˜çš„å„¿ç«¥é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN. METHODS: The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups. RESULTS: A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05). CONCLUSIONS: There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.

Effects of penehyclidine hydrochloride on myocardial ischaemia-reperfusion injury in rats by inhibiting TLR4/MyD88/NF-κB pathway via miR-199a-3p.

This study was to probe the role of penehyclidine hydrochloride (PHC) mediating the impact of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signalling pathway on myocardial ischaemia-reperfusion injury (MI/RI) in rats through miR-199a-3p. The rat MI/RI model was established through ligating left anterior descending (LAD) coronary artery. PHC was injected preoperatively into the model rats, and injected with miR-199a-3p lentiviral vector or TLR4 antagonist (TAK-242). Next, cardiac function of rats was examined by echocardiography, and rat serum indicators, oxidative stress levels and inflammatory factors were detected. HE staining was applied to detect pathological tissue structure, TUNEL staining to detect apoptosis rate, qRCR and western blot to detect miR-199a-3p and TLR4/MyD88/NF-κB expressions in rat myocardial tissues. Dual luciferase reporter experiment was conducted to confirm the relationship between miR-199a-3p and TLR4. In conclusion, PHC suppresses TLR4/MyD88/NF-κB signalling pathway through miR-199a-3p, thereby improving MI/RI in rats.

Current Lifetime of Single-Nanoparticle Collision for Sizing Nanoparticles.

Accurate size analysis of nanoparticles (NPs) is vital for nanotechnology. However, this cannot be realized based on conventional single-nanoparticle collision (SNC) because the current intensity, a thermodynamic parameter of SNC for sizing NPs, is always smaller than the theoretical value due to the effect of NP movements on the electrode surface. Herein, a size-dependent dynamic parameter of SNC, current lifetime, which refers to the time that the current intensity decays to 1/e of the original value, was originally utilized to distinguish differently sized NPs. Results showed that the current lifetime increased with NP size. After taking the current lifetime into account rather than the current intensity, the overlap rates for the peak-type current transients of differently sized Pt NPs (10 and 15 nm) and Au NPs (18 and 35 nm) reduced from 73 and 7% to 45 and 0%, respectively, which were closer to the theoretical values (29 and 0%). Hence, the proposed SNC dynamics-based method holds great potential for developing reliable electrochemical approaches to evaluate NP sizes accurately.

Single-Nanoparticle Collision Electrochemistry Biosensor Based on an Electrocatalytic Strategy for Highly Sensitive and Specific Detection of H7N9 Avian Influenza Virus.

Single-nanoparticle collision electrochemistry (SNCE) has gradually become an attractive analytical method due to its advantages in analytical detection, such as a fast response, low cost, low sample consumption, and in situ real-time detection of analytes. However, the biological analyte's direct detection based on the SNCE blocking mode has the problems of low sensitivity and specificity. In this work, an SNCE biosensor based on SNCE electrocatalytic strategy was used for the detection of H7N9 AIV. Nucleic acid aptamers were introduced to recognize the target virus (H7N9 AIV). After the recognition event, ssDNA1 was released and hybridized with another ssDNA2. Owing to the nicking endonuclease Nt.AlwI-mediated target nucleic acid cyclic amplification, one virus particle can indirectly induce the release of 4.2 × 106 Au NPs that can be counted by the SNCE electrocatalytic strategy. The high conversion efficiency greatly improved the detection sensitivity, and the detection limit was as low as 24.3 fg/mL. Therefore, the constructed biosensor can achieve a highly sensitive and specific detection of H7N9 AIV and show a great potential in bioanalytical application.

Risk of vigabatrin-associated brain abnormalities on MRI: A retrospective and controlled study.

OBJECTIVE: Vigabatrin (VGB) is the first-line treatment for infantile spasms (IS). Previous studies have shown that VGB exposure may cause vigabatrin-associated brain abnormalities on magnetic resonance imaging (MRI) (VABAM). Based on previous studies, this study aimed to go further to explore the possible risk factors and the incidence of VABAM. In addition, diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) were compared to explore whether DWI should be used as a routine examination sequence when MRI is performed in children receiving VGB. METHODS: Children with IS receiving VGB were selected as the study subjects. Whether VABAM occurred or not was categorized as the VABAM group and the non-VABAM group, respectively. Their general clinical data and medication exposure were collected. The possible risk factors of VABAM and different MRI sequences were compared and statistically analyzed. RESULTS: A total of 77 children with IS were enrolled in the study, of which 25 (32.5%) developed VABAM. Twenty-three of the 25 VABAM cases have a peak dosage of VGB between 50 and 150 mg/kg/day. The earliest observation time of VABAM was 30 days. Regression analysis of relevant risk factors showed that the peak dosage of VGB was the risk factor for VABAM. Comparison between different MRI sequences showed that DWI is more sensitive than T2WI to the evaluation of VABAM. SIGNIFICANCE: In our study, the occurrence of VABAM was 32.5%, indicating a higher incidence than in most previous reports. In addition, we once again verified that the peak dosage of VGB was the risk factor of VABAM. Caution should be exercised that our data also suggest that VABAM may occur even using the conventional dosage of VGB (ie, 50-150 mg/kg/day). Therefore, even when using the conventional dosage of VGB, regular MRI examination should be required. Furthermore, DWI sequence should be used as a routine examination sequence when MRI is performed in children with IS who are receiving VGB.

Island Formation History Determines Microbial Species-Area Relationships.

The species-area relationship (SAR) and its mechanisms regarding microbes are not as clear as those of plants and animals; this may result from the impact of sampling effects and the confusion between SAR and distance attenuation. We hypothesize that we can find more accurate microbial SAR curve, after removing these two factors. In this study, 27 leaves of three horticultural plants were selected as island models, and microbial biodiversity assessment was done with HTS (high-throughput sequencing). The separate and small systems using leaves as islands allow us to conduct a comprehensive survey of the microbial biodiversity of the leaves, without disturbance from sampling effects and distance attenuation effects. Interestingly, we did not find microbial SAR in those 27 leaves (also not found in evergreen trees Magnolia grandiflora and Eriobotrya japonica), but we did find significant microbial SAR in deciduous tree Ficus altissima. No significant differences were found between the different trees at the alpha diversity level of microbial biodiversity, but quite different on beta diversity. The results of beta diversity partition showed that F. altissima had the highest similarity of the microbial community among the leaves compared to those of M. grandiflora and E. japonica. Since leaf genesis in deciduous plants is more simultaneous than in evergreen plants; the result suggested that inconsistent historical background of leaf islands may mask microbial SAR. Thus, intensive sampling and consistent historical background are important for understanding microbial SAR.

Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer.

BACKGROUND: Excessive extracellular matrix (ECM) deposition in pancreatic ductal adenocarcinoma (PDAC) severely limits therapeutic drug penetration into tumors and is associated with poor prognosis. Collagen is the most abundant matrix protein in the tumor ECM, which is the main obstacle that severely hinders the diffusion of chemotherapeutic drugs or nanomedicines. METHODS: We designed a collagenase-functionalized biomimetic drug-loaded Au nanoplatform that combined ECM degradation, active targeting, immune evasion, near-infrared (NIR) light-triggered drug release, and synergistic antitumor therapy and diagnosis into one nanoplatform. PDAC tumor cell membranes were extracted and coated onto doxorubicin (Dox)-loaded Au nanocages, and then collagenase was added to functionalize the cell membrane through lipid insertion. We evaluated the physicochemical properties, in vitro and in vivo targeting, penetration and therapeutic efficacy of the nanoplatform. RESULTS: Upon intravenous injection, this nanoplatform efficiently targeted the tumor through the homologous targeting properties of the coated cell membrane. During penetration into the tumor tissue, the dense ECM in the PDAC tissues was gradually degraded by collagenase, leading to a looser ECM structure and deep penetration within the tumor parenchyma. Under NIR irradiation, both photothermal and photodynamic effects were produced and the encapsulated chemotherapeutic drugs were released effectively, exerting a strong synergistic antitumor effect. Moreover, this nanoplatform has X-ray attenuation properties that could serve to guide and monitor treatment by CT imaging. CONCLUSION: This work presented a unique and facile yet effective strategy to modulate ECM components in PDAC, enhance tumor penetration and tumor-killing effects and provide therapeutic guidance and monitoring.

Ultra-thin layered double hydroxide-mediated photothermal therapy combine with asynchronous blockade of PD-L1 and NR2F6 inhibit hepatocellular carcinoma.

BACKGROUND: The efficacy of immune checkpoint blockade (ICB), in the treatment of hepatocellular carcinoma (HCC), is limited due to low levels of tumor-infiltrating T lymphocytes and deficient checkpoint blockade in this immunologically "cool" tumor. Thus, combination approaches are needed to increase the response rates of ICB and induce synergistic antitumor immunity. METHODS: Herein, we designed a pH-sensitive multifunctional nanoplatform based on layered double hydroxides (LDHs) loaded with siRNA to block the intracellular immune checkpoint NR2F6, together with the asynchronous blockade surface receptor PD-L1 to induce strong synergistic antitumor immunity. Moreover, photothermal therapy (PTT) generated by LDHs after laser irradiation modified an immunologically "cold" microenvironment to potentiate Nr2f6-siRNA and anti-PD-L1 immunotherapy. Flow cytometry was performed to assess the immune responses initiated by the multifunctional nanoplatform. RESULTS: Under the slightly acidic tumor extracellular environment, PEG detached and the re-exposed positively charged LDHs enhanced tumor accumulation and cell uptake. The accumulated siRNA suppressed the signal of dual protumor activity in both immune and H22 tumor cells by silencing the NR2F6 gene, which further reduced the tumor burden and enhanced systemic antitumor immunity. The responses include enhanced tumor infiltration by CD4+ helper T cells, CD8+ cytotoxic T cells, and mature dendritic cells; the significantly decreased level of immune suppressed regulator T cells. The therapeutic responses were also attributed to the production of IL-2, IFN-γ, and TNF-α. The prepared nanoparticles also exhibited potential magnetic resonance imaging (MRI) ability, which could serve to guide synergistic immunotherapy treatment. CONCLUSIONS: In summary, the three combinations of PTT, NR2F6 gene ablation and anti-PD-L1 can promote a synergistic immune response to inhibit the progression of primary HCC tumors and prevent metastasis. This study can be considered a proof-of-concept for the targeting of surface and intracellular immune checkpoints to supplement the existing HCC immunotherapy treatments.

Natural recovery from fire disturbance is more favorable than assisted recovery for the restoration of soil nematode-trapping fungi.

A fire is usually considered a severe disturbance factor in the environment. Globally, rising temperatures and increasing human activities have intensified the severity and frequency of fire incidents, and research on post-fire recovery has inevitably become an important focus for ecologists. In terms of the restoration of burned areas, there are usually two primary approaches: natural recovery and assisted recovery. However, very few relevant studies have systematically compared these recovery alternatives, suggesting which one is more favorable to the overall restoration of an ecosystem, especially to the soil microbes that function as indispensable components of ecosystems. In this study, the restoration of soil nematode-trapping fungi (NTF) in natural and assisted recovery environments was compared. The results showed that although the NTF community structures differed among the sample sites, the counts and diversity of the NTF communities in the upper and lower soil layers in the natural recovery area were higher than those in the assisted recovery and unburned control areas. These findings suggest that artificial efforts to help ecosystem recovery after fire negatively affect the speed and quality of soil NTF community recovery. Instead, natural recovery appears to be a more suitable land management choice after fire disturbance.

Four New Sesquiterpenoids from the Rice Fermentation of Antrodiella albocinnamomea.

Albocimea B-E (1-4), four new sesquiterpenoids, and four known compounds, steperoxide A (5), dankasterone (6), 1H-indole-3-carboxylic acid (7), and (+)-formylanserinone B (8), were isolated from the rice fermentation of the fungus Antrodiella albocinnamomea. The structures of new compounds were elucidated by comprehensive spectroscopic techniques, the planar structures of new compounds were determined by comprehensive spectroscopic techniques, and their absolute configurations were confirmed via gauge-independent atomic orbital calculations (GIAO), calculation of the electronic circular dichroism (ECD), and optical rotation (OR). These were determined by spectroscopic data analysis.

Production of Minor Ginsenosides from Panax notoginseng Flowers by Cladosporium xylophilum.

Panax notoginseng flowers have the highest content of saponins compared to the other parts of Panax notoginseng, but minor ginsenosides have higher pharmacological activity than the main natural ginsenosides. Therefore, this study focused on the transformation of the main ginsenosides in Panax notoginseng flowers to minor ginsenosides using the fungus of Cladosporium xylophilum isolated from soil. The main ginsenosides Rb1, Rb2, Rb3, and Rc and the notoginsenoside Fa in Panax notoginseng flowers were transformed into the ginsenosides F2 and Rd2, the notoginsenosides Fd and Fe, and the ginsenoside R7; the conversion rates were 100, 100, 100, 88.5, and 100%, respectively. The transformation products were studied by TLC, HPLC, and MS analyses, and the biotransformation pathways of the major ginsenosides were proposed. In addition, the purified enzyme of the fungus was prepared with the molecular weight of 66.4 kDa. The transformation of the monomer ginsenosides by the crude enzyme is consistent with that by the fungus. Additionally, three saponins were isolated from the transformation products and identified as the ginsenoside Rd2 and the notoginsenosides Fe and Fd by NMR and MS analyses. This study provided a unique and powerful microbial strain for efficiently transformating major ginsenosides in P. notoginseng flowers to minor ginsenosides, which will help raise the functional and economic value of the P. notoginseng flower.

Ultrasensitive Electrochemiluminescence Biosensor Based on Closed Bipolar Electrode for Alkaline Phosphatase Detection in Single Liver Cancer Cell.

An ultrasensitive electrochemiluminescence (ECL) biosensor was proposed based on a closed bipolar electrode (BPE) for the detection of alkaline phosphatase (ALP). For most of the BPE-ECL biosensors, an effective signal amplification strategy was the key to enhance the sensitivity of the system. Herein, the signal amplification strategy of the enzyme catalysis was utilized in the BPE-ECL system. Au nanoparticles (NPs) were electrodeposited on the cathode surface of the ITO electrode to improve the stability and sensitivity of the signal. Compared with the previous BPE-ECL biosensors, the sensitivity was increased by at least 3 orders of magnitude. The biosensor showed high sensitivity and specificity of ALP detection with a detection limit of as low as 3.7 aM. Besides, it was further applied to the detection of ALP in different types of cells and successfully realized ALP detection in single Hep G2 cell, which had a huge application prospect in single biomolecule detection or single cell analysis.