Protection of the receptor binding domain (RBD) dimer against SARS-CoV-2 and its variants.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants achieved immune escape and became less virulent and easily transmissible through rapid mutation in the spike protein, thus the efficacy of vaccines on the market or in development continues to be challenged. Updating the vaccine, exploring compromise vaccination strategies, and evaluating the efficacy of candidate vaccines for the emerging variants in a timely manner are important to combat complex and volatile SARS-CoV-2. This study reports that vaccines prepared from the dimeric receptor-binding domain (RBD) recombinant protein, which can be quickly produced using a mature and stable process platform, had both good immunogenicity and protection in vivo and could completely protect rodents from lethal challenge by SARS-CoV-2 and its variants, including the emerging Omicron XBB.1.16, highlighting the value of dimeric recombinant vaccines in the post-COVID-19 era.

Identification of tanshinone I as cap-dependent endonuclease inhibitor with broad-spectrum antiviral effect.

IMPORTANCE: The spread of avian-borne, tick-borne, and rodent-borne pathogens has the potential to pose a serious threat to human health, and candidate vaccines as well as therapeutics for these pathogens are urgently needed. Tanshinones, especially tanshinone I, were identified as a cap-dependent endonuclease inhibitor with broad-spectrum antiviral effects on negative-stranded, segmented RNA viruses including bandavirus, orthomyxovirus, and arenavirus from natural products, implying an important resource of candidate antivirals from the traditional Chinese medicines. This study supplies novel candidate antivirals for the negative-stranded, segmented RNA virus and highlights the endonuclease involved in the cap-snatching process as a reliable broad-spectrum antiviral target.

Exosomes mediate the antibody-resistant intercellular transmission of porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic enteric coronavirus that causes severe enteritis and lethal watery diarrhea in suckling piglets, leading to tremendous economic losses. Exosomes have been reported to participate in intercellular communication by the transportation of a variety of biological materials, including RNAs, lipids, and proteins. However, PEDV transmission routes have not yet been fully elucidated, and whether exosomes function in PEDV transmission remains unclear. In this study, we extracted and purified exosomes from PEDV-infected Vero cells using a stringent isolation method with a combination of chemical precipitation, ultracentrifugation, and incubation with CD63-labeled magnetic beads. We found that exosomes from PEDV-infected Vero cells contain viral genomic RNA and viral nucleocapsid protein. Furthermore, we demonstrated that the purified exosomes from PEDV-infected cells are capable of transmitting the virus to both PEDV-susceptible and non-susceptible cells. Importantly, exosome-mediated PEDV infection was resistant to neutralization by PEDV-specific neutralizing antibodies that potently neutralized free PEDV. Our study reveals a potential immune evasion mechanism utilized by PEDV and provides new insight into the transmission and infection of this important pathogen.

Advances in mRNA vaccines for viral diseases.

Since the onset of the pandemic caused by severe acute respiratory syndrome coronavirus 2, messenger RNA (mRNA) vaccines have demonstrated outstanding performance. mRNA vaccines offer significant advantages over conventional vaccines in production speed and cost-effectiveness, making them an attractive option against other viral diseases. This article reviewed recent advances in viral mRNA vaccines and their delivery systems to provide references and guidance for developing mRNA vaccines for new viral diseases.

Porcine deltacoronavirus resists antibody neutralization through cell-to-cell transmission.

ABSTRACTPorcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that has been reported to infect a variety of animals and even humans. Cell-cell fusion has been identified as an alternative pathway for the cell-to-cell transmission of certain viruses, but the ability of PDCoV to exploit this transmission model, and the relevant mechanisms, have not been fully elucidated. Herein, we provide evidence that cell-to-cell transmission is the main mechanism supporting PDCoV spread in cell culture and that this efficient spread model is mediated by spike glycoprotein-driven cell-cell fusion. We found that PDCoV efficiently spread to non-susceptible cells via cell-to-cell transmission, and demonstrated that functional receptor porcine aminopeptidase N and cathepsins in endosomes are involved in the cell-to-cell transmission of PDCoV. Most importantly, compared with non-cell-to-cell infection, the cell-to-cell transmission of PDCoV was resistant to neutralizing antibodies and immune sera that potently neutralized free viruses. Taken together, our study revealed key characteristics of the cell-to-cell transmission of PDCoV and provided new insights into the mechanism of PDCoV infection.

Porcine Epidemic Diarrhea Virus nsp7 Inhibits MDA5 Dephosphorylation to Antagonize Type I Interferon Production.

Porcine epidemic diarrhea virus (PEDV) is a reemerging enteropathogenic coronavirus that causes high mortality in piglets and has catastrophic effects on the global pig industry. PEDV-encoded nonstructural protein 7 (nsp7) is an important component of the viral replication and transcription complex, and a previous study reported that it inhibits poly(I:C)-induced type I interferon (IFN) production, but the mechanism by which this occurs remains unclear. Here, we demonstrated that ectopic expression of PEDV nsp7 antagonized Sendai virus (SeV)-induced interferon beta (IFN-ß) production, as well as the activation of transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB) in both HEK-293T and LLC-PK1 cells. Mechanistically, PEDV nsp7 targets melanoma differentiation-associated gene 5 (MDA5) and interacts with its caspase activation and recruitment domains (CARDs), which sequester the interactions between MDA5 and the protein phosphatase 1 (PP1) catalytic subunits (PP1α and PP1γ), thereby suppressing MDA5 S828 dephosphorylation and keeping MDA5 inactive. Furthermore, PEDV infection attenuated MDA5 multimerization and MDA5-PP1α/-γ interactions. We also tested the nsp7 orthologs of five other mammalian coronaviruses and found that all of them except severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nsp7 inhibited MDA5 multimerization and SeV- or MDA5-induced IFN-ß production. Collectively, these results suggest that the inhibition of MDA5 dephosphorylation and multimerization may be a common strategy employed by PEDV and some other coronaviruses to antagonize MDA5-mediated IFN production. IMPORTANCE Since late 2010, a reemerging porcine epidemic diarrhea virus variant with high pathogenesis has swept through most pig farms in many countries, resulting in significant economic losses. Coronavirus nonstructural protein 7 (nsp7), conserved within the family Coronaviridae, combines with nsp8 and nsp12 to form the viral replication and transcription complex that is indispensable for viral replication. However, the function of nsp7 in the infection and pathogenesis of coronaviruses remains largely unknown. Our present study demonstrates that PEDV nsp7 specifically competes with PP1 for binding MDA5 and impedes the PP1-mediated dephosphorylation of MDA5 at S828, thereby blocking MDA5-mediated IFN production, revealing the complex mechanism utilized by PEDV nsp7 to efficiently escape host innate immunity.

Vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway.

Vaccarin is a flavonoid glycoside, which has a variety of pharmacological properties and plays a protective role in diabetes and its complications, but its mechanism is unclear. In this study, we aim to investigate whether histone deacetylase 1(HDAC1), a gene that plays a pivotal role in regulating eukaryotic gene expression, is the target of miR-570-3p in diabetic vascular endothelium, and the potential molecular mechanism of vaccarin regulating endothelial inflammatory injury through miR-570-3p/HDAC1 pathway. The HFD and streptozotocin (STZ) induced diabetes mice model, a classical type 2 diabetic model, was established. The aorta of diabetic mice displayed a decrease of miR-570-3p, the elevation of HDAC1, and inflammatory injury, which were alleviated by vaccarin. Next, we employed the role of vaccarin in regulating endothelial cells miR-570-3p and HDAC1 under hyperglycemia conditions in vitro. We discovered that overexpression of HDAC1 counteracted the inhibitory effect of vaccarin on inflammatory injury in human umbilical vein endothelial cells (HUVECs). Manipulation of miRNA levels in HUVECs was achieved by transfecting cells with miR-570-3p mimic and inhibitor. Overexpression of miR-570-3p could decrease the expression of downstream components of HDAC1 including TNF-α, IL-1ß, and malondialdehyde, while increasing GSH-Px activity in HUVECs under hyperglycemic conditions. Nevertheless, such phenomenon was completely reversed by miR-570-3p inhibitor, and administration of miR-570-3p inhibitor could block the inhibition of vaccarin on HDAC1 and inflammatory injury. Luciferase reporter assay confirmed the 3'- UTR of the HDAC1 gene was a direct target of miR-570-3p. In summary, our findings suggest that vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway. Our study provides a new pathogenic link between deregulation of miRNA expression in the vascular endothelium of diabetes and inflammatory injury and provides new ideas, insights, and choices for the scope of application and medicinal value of vaccarin and some potential biomarkers or targets in diabetic endothelial dysfunction and vascular complications.

Porcine deltacoronavirus accessory protein NS7a possesses the functional characteristics of a viroporin.

Viroporins are virus-encoded proteins that mediate ion channel (IC) activity, playing critical roles in virus entry, replication, pathogenesis, and immune evasion. Previous studies have shown that some coronavirus accessory proteins have viroporin-like activity. Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus that encodes three accessory proteins, NS6, NS7, and NS7a. However, whether any of the PDCoV accessory proteins possess viroporin-like activity, and if so which, remains unknown. In this study, we analyzed the biochemical properties of the three PDCoV-encoded accessory proteins and found that NS7a could enhance the membrane permeability of both mammalian cells and Escherichia coli cells. Indirect immunofluorescence assay and co-immunoprecipitation assay results further indicated that NS7a is an integral membrane protein and can form homo-oligomers. A bioinformation analysis revealed that a putative viroporin domain (VPD) is located within amino acids 69-88 (aa69-88) of NS7a. Experiments with truncated mutants and alanine scanning mutagenesis additionally demonstrated that the amino acid residues 69FLR71 of NS7a are essential for its viroporin-like activity. Together, our findings are the first to demonstrate that PDCoV NS7a possesses viroporin-like activity and identify its key amino acid residues associated with viroporin-like activity.

Preparation and characterization of vaccarin, hypaphorine and chitosan nanoparticles and their promoting effects on chronic wounds healing.

Chronic wounds have become an important factor hindering human health, affecting tens of millions of people worldwide, especially diabetic wounds. Based on the antibacterial properties of chitosan, the angiogenesis promoting effect of vaccarin (VAC) and the anti-inflammatory effect of hypaphorine (HYP), nanoparticles with high bioavailability were prepared. VAC, HYP and chitosan nanoparticles (VAC + HYP-NPS) were used to the treatment of chronic wounds. Transmission electron microscopy (TEM) images showed the nanoparticles were spherical. ZetaPALS showed the potential of nanoparticles were -12.8 ± 5.53 mV and the size were 166.8 ± 29.95 nm. Methyl thiazolyl tetrazolium (MTT) assay showed that VAC + HYP-NPS had no toxicity and the biocompatibility was satisfactory. In the treatment of chronic wounds in diabetic rats, VAC + HYP-NPS significantly promoted the re-epithelialization of chronic wounds and accelerated the healing of chronic wounds. In the process of chronic wounds healing, VAC + HYP-NPS played the antibacterial effect of chitosan, the angiogenic effect of VAC and the anti-inflammatory effect of HYP, and finally promoted the chronic wounds healing. Overall, the developed VAC + HYP-NPS have potential application in chronic wounds healing. In view of the complexity of the causes of chronic wounds, multi-target drug administration may be an effective way to treat chronic wounds.

Induction and modulation of the unfolded protein response during porcine deltacoronavirus infection.

Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus that has the potential for cross-species infection. Many viruses have been reported to induce endoplasmic reticulum stress (ERS) and activate the unfolded protein response (UPR). To date, little is known about whether and, if so, how the UPR is activated by PDCoV infection. Here, we investigated the activation state of UPR pathways and their effects on viral replication during PDCoV infection. We found that PDCoV infection induced ERS and activated all three known UPR pathways (inositol-requiring enzyme 1 [IRE1], activating transcription factor 6 [ATF6], and PKR-like ER kinase [PERK]), as demonstrated by IRE1-mediated XBP1 mRNA cleavage and increased mRNA expression of XBP1s, ATF4, CHOP, GADD34, GRP78, and GRP94, as well as phosphorylated eIF2α expression. Through pharmacologic treatment, RNA interference, and overexpression experiments, we confirmed the negative role of the PERK-eIF2α pathway and the positive regulatory role of the ATF6 pathway, but found no obvious effect of IRE1 pathway, on PDCoV replication. Taken together, our results characterize, for the first time, the state of the ERS response during PDCoV infection and identify the PERK and ATF6 pathways as potential antiviral targets.

Prevalence and risk factors for depression and anxiety in adult patients with epilepsy: Caregivers' anxiety and place of residence do mater.

OBJECTIVES: This study was aimed to assess the prevalence of anxiety and depression and the possible contributions of the caregiver's anxiety and depression, disease status, and socio-demographic characteristics to psychopathological comorbidities among adult patients with epilepsy. METHODS: A total of 262 participants (131 adult patient-caregiver pairs) were enrolled in this study. The Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A) were applied to evaluate the depression and anxiety status among adult patients with epilepsy and their caregivers, respectively. We collected caregivers' anxiety and depression, patients' sociodemographic characteristic data, and disease status as independent variables using stepwise multiple linear regression analysis that were correlated to the degree of anxiety and depression among these adult patients with epilepsy. RESULTS: Among adult patients with epilepsy, 46 (35.11%) subjects showed anxiety symptoms (HAM-A scores > 6), and 48 (36.64%) had depression symptoms (HAM-D scores > 6). Caregivers' anxiety levels and place of residence were significant independent predictors of both anxiety and depression levels among adult patients with epilepsy. CONCLUSIONS: Adult patients with epilepsy are at a high risk of suffering from anxiety and depression. Caregivers' anxiety and place of residence are definite independent predictors for anxiety and depression severity among adult patients with epilepsy. Therefore, clinicians should be careful in closely monitoring the psychological status of adult patients with epilepsy and their caregivers. Furthermore, the government and medical institutions should increase educational awareness about epilepsy and its cure, especially among adult patients with epilepsy who live in rural areas and consider offering a multidisciplinary management program to improve these patients' psychological status.

Preparation of W/O Hypaphorine-Chitosan Nanoparticles and Its Application on Promoting Chronic Wound Healing via Alleviating Inflammation Block.

Chronic wound repair is a common complication in patients with diabetes mellitus, which causes a heavy burden on social medical resources and the economy. Hypaphorine (HYP) has good anti-inflammatory effect, and chitosan (CS) is used in the treatment of wounds because of its good antibacterial effect. The purpose of this research was to investigate the role and mechanism of HYP-nano-microspheres in the treatment of wounds for diabetic rats. The morphology of HYP-NPS was observed by transmission electron microscopy (TEM). RAW 264.7 macrophages were used to assess the bio-compatibility of HYP-NPS. A full-thickness dermal wound in a diabetic rat model was performed to evaluate the wound healing function of HYP-NPS. The results revealed that HYP-NPS nanoparticles were spherical with an average diameter of approximately 50 nm. The cell experiments hinted that HYP-NPS had the potential as a trauma material. The wound test in diabetic rats indicated that HYP-NPS fostered the healing of chronic wounds. The mechanism was through down-regulating the expression of pro-inflammatory cytokines IL-1ß and TNF-α in the skin of the wound, and accelerating the transition of chronic wound from inflammation to tissue regeneration. These results indicate that HYP-NPS has a good application prospect in the treatment of chronic wounds.

A Novel Multiplex Mycotoxin Surface-Enhanced Raman Spectroscopy Immunoassay Using Functional Gold Nanotags on a Silica Photonic Crystal Microsphere Biochip.

A novel multiplex mycotoxin surface-enhanced Raman spectroscopy (SERS) immunoassay was established for the first time on different artificial antigen-modified silica photonic crystal microspheres (SPCMs), which can be integrated into a biochip array to achieve multiplex detection using corresponding antibody-functionalized gold nanoparticles (AuNPs) as the SERS nanotag. The unique optical structure of SPCMs is helpful to find the detection spots easily, accommodate a large amount of probe molecules, and enhance the Raman signal intensity. Such enhancement was confirmed by the simulation result, showing the electric field enhancing effect in SPCMs with AuNPs being 7 times. A competitive SERS immunoassay was established using antigen-modified SPCMs and mycotoxins to compete for binding antibody-functionalized SERS nanotags, displaying broad linear detection ranges of 0.001-0.1 ng/mL for aflatoxin B1 (AFB1), 0.01-10 ng/mL for ochratoxin A (OTA), and 0.001-0.1 ng/mL for zearalenone (ZEN) and low detection limits of 0.82 pg/mL for AFB1, 1.43 pg/mL for OTA, and 1.00 pg/mL for ZEN. In the spiked cereal samples, recovery rates of the method were measured in the range of 70.35-118.04% for the three mycotoxins, which was in agreement with that of the traditional enzyme-linked immunosorbent assay method. The SERS immunoassay for mycotoxin detection also showed high specificity and good repeatability and reproducibility. The new microsphere-based SERS immunoassay biochip only requires a one-step reaction and overcomes the disadvantages of fluorescence and chemiluminescence background signals. The work paves the way for further developing SERS-based microsphere suspension arrays for new targets.

Seed coat mucilages: Structural, functional/bioactive properties, and genetic information.

Seed coat mucilages are mainly polysaccharides covering the outer layer of the seeds to facilitate seed hydration and germination, thereby improving seedling emergence and reducing seedling mortality. Four types of polysaccharides are found in mucilages including xylan, pectin, glucomannan, and cellulose. Recently, mucilages from flaxseed, yellow mustard seed, chia seed, and so on, have been used extensively in the areas of food, pharmaceutical, and cosmetics contributing to stability, texture, and appearance. This review, for the first time, addresses the similarities and differences in physicochemical properties, molecular structure, and functional/bioactive properties of mucilages among different sources; highlights their structure and function relationships; and systematically summarizes the related genetic information, aiming with the intent to explore the potential functions thereby extending their future industrial applications.

Design of an Optimally-Diagnostic Skin Test for Diagnosis of Sensitivity to Eight Allergens: A First-in-Human Study of Dose Escalation and Simultaneous Administration in Chinese Subjects.

BACKGROUND: Eight extracts from common native allergens, Artemisia annua pollen, Platanus pollen, Humulus pollen, Betula platyphylla pollen, Ambrosia artemisiifolia pollen, Blattella germanica, cat dander and dog dander were developed for skin prick test (SPT). Since standardization and composition alone cannot guarantee that the allergen extracts are within the concentration range that give the best chance of a true diagnosis, it is necessary to explore the optimal diagnostic concentration (ODC) of allergens in SPT. OBJECTIVE: To identify the optimal diagnostic concentration of eight allergen extracts in SPT and assess the safety of simultaneous administration. PATIENTS AND METHODS: Patients with a history of allergic disease were enrolled in this two-part open-label, parallel study. In Study 1, 92 patients were enrolled into eight groups according to their disease-causing allergens and were given three increasing concentrations of the corresponding allergen. In Study 2, 20 patients were divided into two concentration groups and were given all of the eight allergens. Safety and sensitivity were evaluated to determine the optimal diagnostic concentration. RESULTS: In Study 1, the sensitivity of seven allergen extracts was >80% at middle and high concentrations, except for Ambrosia artemisiifolia pollen. The optimal diagnostic concentration (in DU/mL) for eight allergens was 33,333, 12,000, 8667, 50,000, 40,000, 3333, 7000, and 5000. In Study 2, the prevalence of adverse events in the two groups was 70% and 80%, respectively. A total of 10 wheals of 8 patients did not subside <24 h after SPTs. CONCLUSION: The eight allergens showed high sensitivity and safety at a certain concentration, which was defined as optimal diagnostic concentration. The results support further clinical research of investigated allergens and our study offers a scheme to determine the ODC of allergens in SPT.

Long-term arsenite exposure decreases autophagy by increased release of Nrf2 in transformed human keratinocytes.

Autophagy dysfunction in arsenite toxicity plays critical roles in cancer development and progression. However, the precise mechanisms of arsenite-induced skin cancer by blocking autophagy remain uncertain. Herein, this study investigated molecular mechanisms of arsenite-induced autophagy dysfunction mediated by nuclear factor erythroid-2 related factor 2 (Nrf2) in human keratinocyte (HaCaT) cells. The effects of long-term arsenite exposure on Nrf2 activation and autophagy were established using a siRNA interference assay and western blots. A specific siRNA of Nrf2 was used to verify that autophagy induced by arsenite can be influenced by Nrf2. Specific inhibitors of PI3K (LY294002) and mTOR (Rapamycin) and siRNA of Nrf2 were employed to verify that upregulation of Nrf2 correlated with activating the PI3K/Akt pathway. Downstream mTOR and Bcl2 were upregulated by Nrf2 signaling, inhibiting autophagy initiation in arsenite-exposed HaCaT cells. In conclusion, our data suggest that long-term exposure to arsenite promotes Nrf2 upregulation via the PI3K/Akt pathway and, along with upregulation of downstream mTOR and Bcl2, contributes to autophagy dysfunction in transformed HaCaT cells. This work provides new insights into the mechanisms underlying arsenite-induced autophagy dysfunction in cancer promotion and malignancy progression.

Predicting seizure freedom with AED treatment in newly diagnosed patients with MRI-negative epilepsy: A large cohort and multicenter study.

OBJECTIVE: We developed and validated a prediction score for predicting the probability of 6-month and 12-month seizure freedom of antiepileptic drug (AED) treatment in newly diagnosed patients with magnetic resonance imaging (MRI)-negative epilepsy. METHODS: The development cohort included 543 consecutive patients from the Epilepsy Center of Henan Provincial People's Hospital, while the validation cohorts included 493 consecutive patients in two independent cohorts. Univariate analysis and a forward and backward elimination of multivariate Cox regression analysis were used to select predictive factors. The performance of the score was evaluated with C-index, calibration plots, and decision curve analysis. The risk stratification was also performed. RESULTS: The score included five routinely available predictors including Circadian rhythms, Electroencephalography before AED treatment, Neuropsychiatric disorders, Perinatal brain injury, and History of central nervous system infection (CENPH score). When applied to the external validation cohort, the score showed good discrimination with C-index (development group: 0.83; validation group: 0.78), and calibration plots indicated well calibration, as well as the decision curve analysis showed good predictive accuracy and clinical values in four cohorts. The points of the score were categorized to the following three probability levels for predicting seizure freedom: high probability (0-83.11 points), medium probability (83.11-122.71 points), and low probability (>122.71 points). And online calculator was established to make this score easily applicable in clinical practice. CONCLUSIONS: We established a simple, practical, and evidence-based prediction score for predicting seizure freedom with AEDs to aid in the clinical consultation and treatment decision for the newly diagnosed patients with MRI-negative epilepsy.

Oral Curcumin via Hydrophobic Porous Silicon Carrier: Preparation, Characterization, and Toxicological Evaluation In Vivo.

Curcumin has antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic activities. However, the clinical application of curcumin has been restricted by the poor water solubility and low bioavailability of this molecule. In this work, hydrophobic porous silicon (pSi) particles were prepared by electrochemical etching method and grafted with the different hydrophobic groups on their surfaces. The loading efficiency of curcumin in pSi has been investigated. The properties of pSi particles have been characterized by scanning electron microscopy (SEM) and Fourier transform-infrared spectroscopy (FTIR). The highest loading efficiency of curcumin can be obtained with pSi surface modified with the octadecyl silane group. The release properties of curcumin in hydrophobic pSi have been researched in vitro and in vivo. The curcumin in the hydrophobic pSi surface keeps a high antioxidant bioactivity. The toxicological evaluation of the hydrophobic pSi particles indicates they have a high in vivo biocompatibility within the observed dose ranges. The hydrophobic pSi particles could provide an effective and controlled release delivery carrier for curcumin, which may provide a new tool platform for the further development of curcumin.

A scale for prediction of response to AEDs in patients with MRI-negative epilepsy.

OBJECTIVES: Antiepileptic drugs (AEDs) are the first choice in magnetic resonance imaging (MRI)-negative patients with epilepsy, although the responses to AEDs are diverse. Preoperative evaluation and postoperative prognosis in MRI-negative epilepsy have been reported. However, there are few tools for predicting the response to AEDs. Herein, we developed an AED response scale based on clinical factors and video-electroencephalography (VEEG) in MRI-negative patients with epilepsy. METHODS: A total of 132 consecutive patients with MRI-negative epilepsy at the Epilepsy Center of Henan Provincial People's Hospital between August 2016 and August 2018 were included. Patients were further divided into drug-responsive epilepsy ([DSE-MRI (-)]; n = 101) and drug-resistant epilepsy ([DRE-MRI (-)]; n = 31) groups. The clinical and VEEG factors were evaluated in univariate analyses and multivariate logistic regression analyses. A scale was derived and the scores categorized into 3 risk levels of DRE-MRI (-). RESULTS: A scale was established based on 4 independent risk factors for DRE-MRI (-). The scale had a sensitivity of 83.87%, specificity of 80.20%, positive likelihood ratio of 4.24, negative likelihood ratio of 0.20, and showed good discrimination with the area under the curve (AUC) of 0.886 (0.826-0.946). The categorization of the risk score based on this scale was: low risk (0-3 points), medium risk (3-5 points), and high risk (>5 points). CONCLUSION: We established a DRE-MRI (-) scale with a good sensitivity and specificity, which may be useful for clinicians when making medical decisions in patients with MRI-negative epilepsy.