A microscope-assisted endoscopic transcanal transpromontorial approach for vestibular schwannoma resection: a preliminary report.

OBJECTIVE: To evaluate the feasibility of a microscope-assisted endoscopic transcanal transpromontorial approach (METTA) for the removal of small vestibular schwannomas (VS) limited to the internal auditory canal (IAC), and introduce a modification without external auditory canal (EAC) closure. METHODS: Between August 2018 and February 2019, seven patients with intrameatal VS underwent surgery in our center, endoscopic transcanal transpromontorial approach was applied in the first 2 patients and the rest 5 patients were operated via METTA. Treatment outcomes including efficacy of tumor resection, facial nerve outcome, operation time and post-operative course were recorded and analyzed. RESULTS: All seven patients were pathologically confirmed to have intrameatal VS. Total tumor removal was achieved in all cases. Two patients experienced cerebrospinal fluid leakage which resolved spontaneously within 5 days. The average operation time was 161.41 ± 18.42 min. All patients presented normal facial nerve function 1 month after surgery. CONCLUSION: The METTA was effective in the removal of intrameatal VS. It can be an alternative surgical option for intrameatal VS with no serviceable hearing.

EndophilinA2 protects against angiotensin II-induced cardiac hypertrophy by inhibiting angiotensin II type 1 receptor trafficking in neonatal rat cardiomyocytes.

Cardiac hypertrophy is one of the major risk factors for chronic heart failure. The role of endophilinA2 (EndoA2) in clathrin-mediated endocytosis and clathrin-independent endocytosis is well documented. In the present study, we tested the hypothesis that EndoA2 protects against angiotensin II (Ang II)-induced cardiac hypertrophy by mediating intracellular angiotensin II type 1 receptor (AT1-R) trafficking in neonatal rat cardiomyocytes (NRCMs). Cardiac hypertrophy was evaluated by using cell surface area and quantitative RT-PCR (qPCR) analyses. For the first time, we found that EndoA2 attenuated cardiac hypertrophy and fibrosis induced by Ang II. Moreover, EndoA2 inhibited apoptosis induced by excessive endoplasmic reticulum stress (ERS), which accounted for the beneficial effects of EndoA2 on cardiac hypertrophy. We further revealed that there was an interaction between EndoA2 and AT1-R.The expression levels of EndoA2, which inhibits AT1-R transport from the cytoplasm to the membrane, and the interaction between EndoA2 and AT1-R were obviously decreased after Ang II treatment. Furthermore, Ang II inhibited the co-localization of AT1-R with GRP-78, which was reversed by EndoA2 overexpression. In conclusion, our results suggested that EndoA2 plays a role in protecting against cardiac hypertrophy induced by Ang II, possibly by inhibiting AT1-R transport from the cytoplasm to the membrane to suppress signal transduction.

Autophagy is involved in the protective effect of endophilin A2 on H2O2-induced apoptosis in H9C2 cardiomyocytes.

Apoptosis plays a critical role in normal embryonic development and tissue homeostasis regulation. EndophilinA2 (EndoA2) is widely reported to regulate endocytosis. Additionally, EndoA2 has been demonstrated to be involved in tumor metastasis, neuroregulation and vascular function. In this study, we used siRNA and Ad-EndoA2 transfection strategy to investigate whether EndoA2 provides a protective effect against apoptosis induced by H2O2 in H9C2 cardiomyocytes and the underlying mechanisms. We found that EndoA2 siRNA knockdown promoted H2O2-induced apoptosis in H9C2 cardiomyocytes, evidenced by decreased cell number, increased apoptotic cells, and activation of caspase-3. In contrast, EndoA2 overexpression showed the opposite effects and inhibited H2O2-induced apoptosis in H9C2 cardiomyocytes. Further studies revealed that EndoA2 overexpression strengthened autophagy, evidenced by the increased LC3 II/I ratio and P62 degradation, whereas EndoA2 siRNA knockdown produced the opposite effects. Furthermore, we revealed that there was an interaction between Bif-1 and Beclin-1. Upon H2O2 treatment, the association of Bif-1 and Beclin-1 remarkably increased. EndoA2 overexpression further promoted the binding of Bif-1 with Beclin-1, whereas EndoA2 siRNA knockdown reduced this association. These data strongly suggested that EndoA2 inhibited H2O2-induced apoptosis in H9C2 cardiomyocytes, possibly by promoting Bif-1 to form a complex with Beclin-1 and strengthening autophagy. This study provides a novel target for heart diseases.

The biomedical knowledge graph of symptom phenotype in coronary artery plaque: machine learning-based analysis of real-world clinical data.

A knowledge graph can effectively showcase the essential characteristics of data and is increasingly emerging as a significant means of integrating information in the field of artificial intelligence. Coronary artery plaque represents a significant etiology of cardiovascular events, posing a diagnostic challenge for clinicians who are confronted with a multitude of nonspecific symptoms. To visualize the hierarchical relationship network graph of the molecular mechanisms underlying plaque properties and symptom phenotypes, patient symptomatology was extracted from electronic health record data from real-world clinical settings. Phenotypic networks were constructed utilizing clinical data and protein‒protein interaction networks. Machine learning techniques, including convolutional neural networks, Dijkstra's algorithm, and gene ontology semantic similarity, were employed to quantify clinical and biological features within the network. The resulting features were then utilized to train a K-nearest neighbor model, yielding 23 symptoms, 41 association rules, and 61 hub genes across the three types of plaques studied, achieving an area under the curve of 92.5%. Weighted correlation network analysis and pathway enrichment were subsequently utilized to identify lipid status-related genes and inflammation-associated pathways that could help explain the differences in plaque properties. To confirm the validity of the network graph model, we conducted coexpression analysis of the hub genes to evaluate their potential diagnostic value. Additionally, we investigated immune cell infiltration, examined the correlations between hub genes and immune cells, and validated the reliability of the identified biological pathways. By integrating clinical data and molecular network information, this biomedical knowledge graph model effectively elucidated the potential molecular mechanisms that collude symptoms, diseases, and molecules.

[Pollution Characteristics, Source Apportionment, and Meteorological Response of Water-soluble Ions in PM2.5 in Xinxiang, North China].

Pollution variation, source characteristics, and meteorological effects of water-soluble inorganic ions (WSIIs) in PM2.5 were analyzed in Xinxiang city, Henan Province. PM2.5 samples and their chemical components were monitored online by using URG-9000 in four seasons:winter (January, 2022), spring (April, 2022), summer (July, 2022), and fall (October, 2022). The results showed that the TWSIIs had the same seasonal fluctuations as PM2.5. The average seasonal concentrations of WSIIs ranged from 19.62-72.15 µg·m-3, accounting for more than 60% of PM2.5, demonstrating that WSIIs were the major components of PM2.5. The annual concentration value of NO3-/SO42- was 2.11, which showed an increasing trend, suggesting predominantly mobile sources for secondary inorganic aerosols (SNA). Further, the molar concentration value [NH4+]/[NO3-] was 1.95, demonstrating that agriculture emissions were the dominant contributors to atmospheric nitrogen. Furthermore, the backward trajectory analysis showed that the concentrations of Ca2+ and Mg2+ were higher when the northeasterly wind prevailed and the wind speed was high. High values of SOR and NOR were correlated with low temperatures and high relative humidity (T < 8℃, RH > 60%), demonstrating that more gaseous precursors were converted into sulfate and nitrate. At high temperatures (T > 24℃), there was no apparent high NOR value like that for SOR, mainly due to the decomposition of NH4NO3 at high temperatures. Finally, backward trajectories associated with the PMF-resolved results were used to explore the regional transport characteristics. The results illustrated that dust sources in the study areas were mainly influenced by air trajectories originating from the northwest regions, whereas secondary sulfate, secondary nitrate, and biomass sources contributed more to WSIIs when wind speed and altitude air masses were low in the area surrounding the observation site.

Effect of botanical drugs in improving symptoms of hypertensive nephropathy: Analysis of real-world data, retrospective cohort, network, and experimental assessment.

Background/aim: Hypertensive nephropathy (HN) is a common complication of hypertension. Traditional Chinese medicine has long been used in the clinical treatment of Hypertensive nephropathy. However, botanical drug prescriptions have not been summarized. The purpose of this study is to develop a prescription for improving hypertensive nephropathy, explore the evidence related to clinical application of the prescription, and verify its molecular mechanism of action. Methods: In this study, based on the electronic medical record data on Hypertensive nephropathy, the core botanical drugs and patients' symptoms were mined using the hierarchical network extraction and fast unfolding algorithm, and the protein interaction network between botanical drugs and Hypertensive nephropathy was established. The K-nearest neighbors (KNN) model was used to analyze the clinical and biological characteristics of botanical drug compounds to determine the effective compounds. Hierarchical clustering was used to screen for effective botanical drugs. The clinical efficacy of botanical drugs was verified by a retrospective cohort. Animal experiments were performed at the target and pathway levels to analyze the mechanism. Results: A total of 14 botanical drugs and five symptom communities were obtained from real-world clinical data. In total, 76 effective compounds were obtained using the K-nearest neighbors model, and seven botanical drugs were identified as Gao Shen Formula by hierarchical clustering. Compared with the classical model, the Area under the curve (AUC) value of the K-nearest neighbors model was the best; retrospective cohort verification showed that Gao Shen Formula reduced serum creatinine levels and Chronic kidney disease (CKD) stage [OR = 2.561, 95% CI (1.025-6.406), p < 0.05]. With respect to target and pathway enrichment, Gao Shen Formula acts on inflammatory factors such as TNF-α, IL-1ß, and IL-6 and regulates the NF-κB signaling pathway and downstream glucose and lipid metabolic pathways. Conclusion: In the retrospective cohort, we observed that the clinical application of Gao Shen Formula alleviates the decrease in renal function in patients with hypertensive nephropathy. It is speculated that Gao Shen Formula acts by reducing inflammatory reactions, inhibiting renal damage caused by excessive activation of the renin-angiotensin-aldosterone system, and regulating energy metabolism.

Value of serum free prostate-specific antigen density in the diagnosis of prostate cancer.

PURPOSE: To investigate the value of serum free prostate-specific antigen density (fPSAD) in the diagnosis of prostate cancer (PCa). METHODS: The data of 558 patients who underwent transrectal ultrasound-guided prostate biopsy were retrospectively analyzed. According to the pathological results, the patients were divided into a PCa group and a benign prostatic hyperplasia (BPH) group. Receiver operating characteristic curves were plotted, based on which the sensitivity, specificity, Youden index, concordance, and kappa values of free prostate-specific antigen (fPSA), the free-to-total f/tPSA, prostate-specific antigen density (PSAD), the free-to-total (f/t)/PSAD ratio, and fPSAD were compared. The patients were divided into three groups by PSA levels (PSA < 4 ng/mL, PSA = 4-10 ng/mL, and PSA > 10 ng/mL), into three groups by age (age < 60 year, age = 60-80y, and age > 80 years), and into two groups by prostate volume (PV) (PV ≤ 80 mL and PV > 80 mL) to compare the sensitivity, specificity, and concordance of indicators. RESULTS: tPSA, PSAD, (f/t)/PSAD, and fPSAD had high accuracy in predicting PCa with AUC values of 0.820, 0.900, 0.846, and 0.867. fPSAD showed lower diagnostic sensitivity but significantly higher specificity and concordance for PCa than tPSA, f/tPSA, (f/t)/PSAD, or PSAD. Thus, fPSAD had the highest accuracy in the diagnosis of PCa. In the groups with different PSA, age, and PV stratification, the concordance of fPSAD was significantly higher (88.61%, 90.74%, and 90.38%) than that of other indicators. CONCLUSION: With the optimal cutoff value of 0.062, fPSAD has a higher diagnostic value for PCa than tPSA, f/tPSA, (f/t)/PSAD, and PSAD, and can well predict the risk of PCa, significantly improve the clinical diagnostic rate of PCa, and reduce unnecessary biopsy.

Blood glucose mediated the effects of cognitive function impairment related to aluminum exposure in Chinese aluminum smelting workers.

OBJECT: To explore the effects of occupational aluminum exposure on workers' cognitive function and blood glucose concentration, and to analyze whether blood glucose concentration can mediate the cognitive changes caused by aluminum. METHOD: Our study recruited 375 workers from an aluminum factory in northern China. We collected the fasting elbow venous blood of the workers, measured their fasting blood glucose concentration (FBG), and used ICP-MS to determine plasma aluminum concentration (P-Al) as an indicator of internal exposure. The Montreal Cognitive Assessment (MoCA), was used to assess the cognitive function of workers. Generalized linear model was used to analyze the association of P-Al with cognitive function and blood glucose concentration, and the restricted cubic spline model was used to fit the dose-response relationship. We also conducted a mediation effect analysis. RESULT: We observed the dose-response relationship, that is, as the P-Al increased, sum of MoCA, visuospatial/executive, naming, language, and abstraction scores decreased, and the blood glucose concentration increased. For every e-fold increase in P-Al, sum of MoCA, visuospatial/executive, naming, language, and abstraction scores decreased by 0.328 points, 0.120 points, 0.059 points, 0.060 points, and 0.083 points, respectively, and FBG rose by 0.109 mmol/L. FBG has a significant mediating effect between P-Al and sum of MoCA (P for mediator=0.042), and it could explain 10.7% of the effect of cognitive level related to P-Al. CONCLUSION: Occupational aluminum exposure negatively affected the cognitive function of workers and positively affected FBG. FBG may partially explain the impact of occupational aluminum exposure on workers' cognitive function.

Predicting Coupled Herbs for the Treatment of Hypertension Complicated with Coronary Heart Disease in Real-World Data Based on a Complex Network and Machine Learning.

Hypertension and coronary heart disease are the most common cardiovascular diseases, and traditional Chinese medicine is applied as an auxiliary treatment for common cardiovascular diseases. This study is based on 3 years of electronic medical record data from the Affiliated Hospital of Shandong University of Traditional Chinese Medicine. A complex network and machine learning algorithm were used to establish a screening model of coupled herbs for the treatment of hypertension complicated with coronary heart disease. A total of 5688 electronic medical records were collected to establish the prescription network and symptom database. The hierarchical network extraction algorithm was used to obtain core herbs. Biological features of herbs were collected from public databases. At the same time, five supervised machine learning models were established based on the biological features of the coupled herbs. Finally, the K-nearest neighbor model was established as a screening model with an AUROC of 91.0%. Seventy coupled herbs for adjuvant treatment of hypertension complicated with coronary heart disease were obtained. It was found that the coupled herbs achieved the purpose of adjuvant therapy mainly by interfering with cytokines and regulating inflammatory and metabolic pathways. These results show that this model can integrate the molecular biological characteristics of herbs, preliminarily screen combinations of herbs, and provide ideas for explaining the value in clinical applications.

[Effect of naoxintong capsule on the vascular endothelial function and the infarct size of patients with acute myocardial infarction].

OBJECTIVE: To observe the effect of Naoxintong Capsule (NC) on the vascular endothelial function and the infarct size of patients with acute myocardial infarction (AMI). METHODS: One hundred and four patients with AMI were randomly assigned to the NC group (Group A, 36 cases), the Tongguan Capsule group (Group B, 32 cases), and the conventional Western medicine group (Group C, 36 cases). The conventional Western medicine was given to the three groups. NC was additionally given to Group A, and Tongguan Capsule was additionally given to Group B. The therapeutic course for all was 4 weeks. The plasma nitric oxide (NO), endothelin (ET), von Willebrand factor (vWF) were detected in the 3 groups before and after treatment. The inner diameter of brachial artery was examined by ultrasonograph. The flow-mediated dilation (FMD) and the nitroglycerin-mediated dilation (NMD) were calculated. The ECG QRS integral and the infarct size were assessed. RESULTS: There was no significant difference in the vascular endothelial function, ECG QRS integral, or the infarct size among the three groups before treatment (P > 0.05). Compared with before treatment, NO and NMD obviously increased after treatment in Group A and Group B, while the vWF and the infarct size obviously decreased in Group A, all showing statistical difference (P < 0.05). Compared with those in Group C, the NO, FMD, NMD significantly increased and ET obviously decreased in Group A and B after treatment (P < 0.05). The ECG QRS integral and the infarct size also decreased, with statistically significant differences in Group A (P < 0.05). Better effects on improving NO, NMD, and vWF were obtained in Group A than in Group B (P < 0.05). CONCLUSION: NC could reduce the infarct size of AMI patients possibly through improving the vascular endothelial function.

Summarizing the Effective Herbs for the Treatment of Hypertensive Nephropathy by Complex Network and Machine Learning.

Hypertensive nephropathy is a common complication of hypertension. Traditional Chinese medicine has been used in the clinical treatment of hypertensive nephropathy for a long time, but the commonly used prescriptions have not been summarized, and the basic therapeutic approaches have not been discussed. Based on data from 3 years of electronic medical records of traditional Chinese medicine used at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, a complex network and machine learning algorithm was used to explore the prescribed herbs of traditional Chinese medicine in the treatment of hypertensive nephropathy (HN). In this study, complex network algorithms were used to describe traditional Chinese medicine prescriptions for HN treatment. The Apriori algorithm was used to analyze the compatibility of these treatments with modern medicine. Data on the targets and regulatory genes related to hypertensive nephropathy and the herbs that affect their expression were obtained from public databases, and then, the signaling pathways enriched with these genes were identified on the basis of their participation in biological processes. A clustering algorithm was used to analyze the therapeutic pathways at multiple levels. A total of 1499 prescriptions of traditional Chinese medicines used for the treatment of hypertensive renal damage were identified. Fourteen herbs used to treat hypertensive nephropathy act through different biological pathways: huangqi, danshen, dangshen, fuling, baizhu, danggui, chenpi, banxia, gancao, qumai, cheqianzi, ezhu, qianshi, and niuxi. We found the formulae of these herbs and observed that they could downregulate the expression of inflammatory cytokines such as TNF, IL1B, and IL6 and the NF-κB and MAPK signaling pathways to reduce the renal inflammatory damage caused by excessive activation of RAAS. In addition, these herbs could facilitate the deceleration in the decline of renal function and relieve the symptoms of hypertensive nephropathy. In this study, the traditional Chinese medicine approach for treating hypertensive renal damage is summarized and effective treatment prescriptions were identified and analyzed. Data mining technology provided a feasible method for the collation and extraction of traditional Chinese medicine prescription data and provided an objective and reliable tool for use in determining the TCM treatments of hypertensive nephropathy.

Identification of Hypertension Subgroups through Topological Analysis of Symptom-Based Patient Similarity.

OBJECTIVE: To obtain the subtypes of the clinical hypertension population based on symptoms and to explore the relationship between hypertension and comorbidities. METHODS: The data set was collected from the Chinese medicine (CM) electronic medical records of 33,458 hypertension inpatients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between July 2014 and May 2017. Then, a hypertension disease comorbidity network (HDCN) was built to investigate the complicated associations between hypertension and their comorbidities. Moreover, a hypertension patient similarity network (HPSN) was constructed with patients' shared symptoms, and 7 main hypertension patient subgroups were identified from HPSN with a community detection method to exhibit the characteristics of clinical phenotypes and molecular mechanisms. In addition, the significant symptoms, diseases, CM syndromes and pathways of each main patient subgroup were obtained by enrichment analysis. RESULTS: The significant symptoms and diseases of these patient subgroups were associated with different damaged target organs of hypertension. Additionally, the specific phenotypic features (symptoms, diseases, and CM syndromes) were consistent with specific molecular features (pathways) in the same patient subgroup. CONCLUSION: The utility and comprehensiveness of disease classification based on community detection of patient networks using shared CM symptom phenotypes showed the importance of hypertension patient subgroups.

Application of Fourier transform near-infrared spectroscopy combined with GC in rapid and simultaneous determination of essential components in Amomum villosum.

A method is described using rapid and sensitive Fourier transform near-infrared spectroscopy combined with Gas Chromatograpy internal standard method detection for the simultaneous identification and determination of three bioactive compounds in Amomum villosum samples. Partial least squares regression is selected as the analysis type and multiplicative scatter correction, second derivative, and SNV were adopted for the spectral pretreatment. The correlation coefficients (R) of the calibration models were above 0.95 and the root mean square error of predictions were under 0.8. The developed models were applied to unknown samples with satisfantory results. The established method was validated and can be applied to the intrinsic quality control of Amomum villosum.

[Seasonal Variation, Source Identification, and Health Risk of PM2.5-bound Metals in Xinxiang].

This study analyzed the seasonal variation, sources, and source-specific health risks of PM2.5-bound metals in Xinxiang city, Henan province. A total of 112 daily PM2.5 samples were collected over four consecutive seasons during 2019-2020. In total, 19 elements were identified using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The annual concentrations of PM2.5 and 11 heavy metals were calculated to be (66.25±35.73) µg·m-3 and (1.32±0.84) µg·m-3, respectively. Strong seasonal variations were observed in PM2.5 concentrations and the concentrations of associated metal elements, with the lowest concentrations all occurring in summer. The highest concentrations of dust-related elements (e.g., Al, Ca, Fe, Mg,and Ti) were recorded in spring, differing significantly from other elements, which all exhibited the highest mass concentrations in winter. The results apportioned from positive matrix factorization (PMF) and potential source contribution function (PSCF) models showed that the major sources of PM2.5-bound elements were Ni-and Co-related emissions (5.8%), motor vehicles (13.7%), Cd-related emissions(5.1%), combustion emissions (18.2%), and dust (57.3%). Health risk models showed that there were no obvious non-carcinogenic risks associated with these metals, because their hazard quotient (HQ) values were all below 1. Lifetime carcinogenic risks of the five apportioned sources were all higher than the acceptable level (1×10-6). Of these five sources, combustion emissions were the largest contributors to cancer risk (8.74×10-6, 36.9%) and non-cancer risk (0.60, 25.6%). This study suggests that control strategies to mitigate exposure risk in Xinxiang should emphasize reducing the sources of combustion emissions.

[Analysis on associated risk factors and syndrome types in diabetes mellitus type 2 patients complicated with non-alcoholic fatty liver].

OBJECTIVE: To explore the risk factors and the main TCM syndrome types associated with the diabetes mellitus type 2 (DM2) patients complicated with non-alcoholic fatty liver (FL). METHODS: Adopted controlled trial method, the age, stature, body weight, and body mass index (BMI) of 180 DM2 patients were compared with those complicated with or without FL. And some related laboratory indexes, including the age, stature, body weight, BMI, fasting blood glucose (FBG), C-peptide (CP), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), high and low density lipoprotein cholesterol (HDL-C and LDL-C), and 2 h post-prandial CP (2 h CP), were compared as well. Moreover, patients' TCM syndrome types were classified. RESULTS: No significant differences were found between DM2 patients complicated with or without FL in aspects of FBG, HbA1c, TC, LDL-C and age, stature (P > 0.05), but significant difference did show between them in aspects of CP (4.09 +/- 2.40 microg/L vs 2.47 +/- 1.74 microg/L), 2h CP (6.38 +/- 5.46 microg/L vs 4.35 +/- 2.92 microg/L), TG (2.81 +/- 2.33 mmol/L vs 1.93 +/- 1.92 mmol/L), HDL-C (1.07 +/- 0.06 mmol/L vs 1.19 +/- 0.32 mmol/L) as well as in body weight (73.4 +/- 11.7 kg vs 61.4 +/- 10.1 kg) and BMI (26.0 +/- 3.67 vs 22.8 +/- 3.23), respectively (P < 0.05 or P < 0.01). Moreover, phlegm-dampness type was more liable to appear in DM2 patients complicated FL. CONCLUSIONS: Obesity, insulin resistance and lipid metabolism disorder are the chief risk factors in DM2 patients complicated with FL and phlegm-dampness is the chief pathogenesis.

Rational Engineering and Characterization of an mAb that Neutralizes Zika Virus by Targeting a Mutationally Constrained Quaternary Epitope.

Following the recent emergence of Zika virus (ZIKV), many murine and human neutralizing anti-ZIKV antibodies have been reported. Given the risk of virus escape mutants, engineering antibodies that target mutationally constrained epitopes with therapeutically relevant potencies can be valuable for combating future outbreaks. Here, we applied computational methods to engineer an antibody, ZAb_FLEP, that targets a highly networked and therefore mutationally constrained surface formed by the envelope protein dimer. ZAb_FLEP neutralized a breadth of ZIKV strains and protected mice in distinct in vivo models, including resolving vertical transmission and fetal mortality in infected pregnant mice. Serial passaging of ZIKV in the presence of ZAb_FLEP failed to generate viral escape mutants, suggesting that its epitope is indeed mutationally constrained. A single-particle cryo-EM reconstruction of the Fab-ZIKV complex validated the structural model and revealed insights into ZAb_FLEP's neutralization mechanism. ZAb_FLEP has potential as a therapeutic in future outbreaks.