Regulatory T cells as crucial trigger and potential target for hyperprogressive disease subsequent to PD-1/PD-L1 blockade for cancer treatment.

PD-1/PD-L1 blockade therapy has brought great success to cancer treatment. Nevertheless, limited beneficiary populations and even hyperprogressive disease (HPD) greatly constrain the application of PD-1/PD-L1 inhibitors in clinical treatment. HPD is a special pattern of disease progression with rapid tumor growth and even serious consequences of patient death, which requires urgent attention. Among the many predisposing causes of HPD, regulatory T cells (Tregs) are suspected because they are amplified in cases of HPD. Tregs express PD-1 thus PD-1/PD-L1 blockade therapy may have an impact on Tregs which leads to HPD. Tregs are a subset of CD4+ T cells expressing FoxP3 and play critical roles in suppressing immunity. Tregs migrate toward tumors in the presence of chemokines to suppress antitumor immune responses, causing cancer cells to grow and proliferate. Studies have shown that deleting Tregs could enhance the efficacy of PD-1/PD-L1 blockade therapy and reduce the occurrence of HPD. This suggests that immunotherapy combined with Treg depletion may be an effective means of avoiding HPD. In this review, we summarized the immunosuppressive-related functions of Tregs in antitumor therapy and focused on advances in therapy combining Tregs depletion with PD-1/PD-L1 blockade in clinical studies. Moreover, we provided an outlook on Treg-targeted HPD early warning for PD-1/PD-L1 blockade therapy.

Preparation and adjuvanticity against PCV2 of Viola philippica polysaccharide loaded in Chitosan-Gold nanoparticle.

The present Porcine circovirus type 2 virus (PCV2) vaccine adjuvants suffer from numerous limitations, such as adverse effects, deficient cell-mediated immune responses, and inadequate antibody production. In this study, we explored the potential of a novel nanoparticle (CS-Au NPs) based on gold nanoparticles (Au NPs) and chitosan (CS) that modified Viola philippica polysaccharide (VPP) as efficient adjuvants for PCV2 vaccine. The characterization demonstrated that CS-Au-VPP NPs had a mean particle size of 507.42 nm and a zeta potential value of -21.93 mV. CS-Au-VPP NPs also exhibited good dispersion and a stable structure, which did not alter the polysaccharide properties. Additionally, the CS-Au-VPP NPs showed easy absorption and utilization by the organism. To investigate their immune-enhancing potential, mice were immunized with a mixture of CS-Au-VPP NPs and PCV2 vaccine. The evaluation of relevant immunological indicators, including specific IgG antibodies and their subclasses, cytokines, and T cell subpopulations, confirmed their immune-boosting effects. The in vivo experiments revealed that the medium-dose CS-Au-VPP NPs significantly elevated the levels of specific IgG antibodies and their subclasses, cytokines, and T cell subpopulations in PCV2-immunized mice. These findings suggest that CS-Au-VPP NPs can serve as a promising vaccine adjuvant due to their stable structure and immunoenhancement capabilities.

Effect of resveratrol on herpesvirus encephalitis: Evidences for its mechanisms of action.

BACKGROUND: Herpes simplex virus type 1 (HSV-1)-induced herpes simplex encephalitis (HSE) has a high mortality rate in clinically immunocompromised patients, while recovered patients often experience neurological sequelae due to neuroinflammation. Nucleoside drugs and nucleoside analogues such as acyclovir and ganciclovir are mainly used in clinical treatment, and the emergence of resistant viral strains makes the development of new anti-herpesvirus encephalitis drugs urgent. Resveratrol is a multifunctional, plant-derived bioactive compound and its antiviral potential is attracting much attention. PURPOSE: This study aimed to investigate the anti-HSV-1 mechanism of resveratrol in microglial cells and in the HSE mouse model. METHODS: The antiviral effect of resveratrol on HSV-1 infection was investigated by plaque assay, virus titer, immunofluorescence, Western blot and time-of-addition assay. The influence of resveratrol on stimulator of interferon gene (STING)/Nuclear Factor kappa B (NF-κB) signaling pathway-mediated neuroinflammation was examined by Western blot, RT-qPCR and ELISA. The interaction between resveratrol and STING/heat shock protein 90 beta (HSP90ß) was evaluated by molecular modeling, co-immunoprecipitation, and drug affinity responsive target stability assay. The therapeutic effect of resveratrol on HSE was evaluated in the HSE mouse model by analyzing weight loss, neurodegenerative symptoms and histopathological scores. RESULTS: Resveratrol inhibited the early process of HSV-1 infection, and interfered with the STING/NF-κB signaling pathway to attenuate HSV-1-induced neuroinflammation and microglial M1 polarization, independent of its classical target Sirtuin1. Mechanistically, resveratrol completely bound to Glu515 and Lys491 of HSP90ß, thus disrupting the HSP90ß-STING interaction and promoting STING degradation. Resveratrol also significantly alleviated viral encephalitis and neuroinflammation caused by HSV-1 in the HSE mouse model. CONCLUSION: Resveratrol acted as a non-classical HSP90ß inhibitor, binding to the STING-HSP90ß interaction site to promote STING degradation and attenuate HSV-1-induced encephalitis and neuroinflammation. These findings suggest the alternative strategy of targeting HSP90ß and resveratrol-mediated inhibition of HSP90ß as a potential antiviral approach.

Metformin as anticancer agent and adjuvant in cancer combination therapy: Current progress and future prospect.

Metformin, as the preferred antihyperglycemic drug for type 2 diabetes, has been found to have a significant effect in inhibiting tumor growth in recent years. However, metformin alone in cancer treatment has the disadvantages of high dose concentrations and few targeted cancer types. Increasing studies have confirmed that metformin can be used in combination with conventional anticancer therapy to obtain more promising clinical benefits, which is expected to be rapidly transformed and applied in clinic. Some combination therapy strategies including metformin combined with chemotherapy, radiotherapy, targeted therapy and immunotherapy have been proven to have more significant antitumor effects and longer survival time than monotherapy. In this review, we summarize the synergistic antitumor effects and mechanisms of metformin in combination with other current conventional anticancer therapies. In addition, we update the research progress and the latest prospect of the metformin-combined application in the cancer treatment. This work could provide more evidence and future direction for the clinical application of metformin in antitumor.

Awareness, attitudes and first aid knowledge of epilepsy among university students - A cross-sectional study in Henan Province, China.

PURPOSE: Epilepsy is a debilitating disease that can lead to series of social and psychological issues, impairing the quality of life of people with epilepsy (PWE). This survey aimed to investigate the awareness, attitudes, and first-aid knowledge of epilepsy in university students METHOD: This cross-sectional study was conducted in Henan Province, China between January 1 and April 30, 2022. Students majored in education, medicine, science and engineering from 8 universities attended the study. The survey questionnaire comprised 28 questions covering 4 sections: demographic characteristics, awareness of epilepsy, attitudes toward PWE and knowledge of first aid for seizures. RESULTS: A total of 2376 university students completed the questionnaire. 94.7% heard of epilepsy. In the first aid knowledge section, individual question was correctly answered by at least 50% students, 9.3% students correctly answered all questions. Attitude toward PWE was independently (R2 =0.108, F=73.227, p < 0.001) associated with both awareness of epilepsy (B=0.411, p < 0.001) and first aid knowledge of epilepsy (B=0.047, p = 0.001). Among the three majors, medical students had more positive attitudes toward PWE than students majored in education, science and engineering (p < 0.05). However, medical students performed worse among the groups when answering the first aid knowledge questions. CONCLUSION: This survey showed that university students in Central China had a good awareness of epilepsy. For medical students, improvements are necessary for the awareness of the first aid knowledge for seizure.

Construction of machine learning models for recognizing comorbid anxiety in epilepsy patients based on their clinical and quantitative EEG features.

BACKGROUND: This study aimed to construct prediction models for the recognizing of anxiety disorders (AD) in patients with epilepsy (PWEs) by combining clinical features with quantitative electroencephalogram (qEEG) features and using machine learning (ML). METHODS: Nineteen clinical features and 20-min resting-state EEG were collected from 71 PWEs comorbid with AD and another 60 PWEs without AD who met the inclusion-exclusion criteria of this study. The EEG were preprocessed and 684 Phase Locking Value (PLV) and 76 Lempel-Ziv Complexity (LZC) features on four bands were extracted. The Fisher score method was used to rank all the derived features. We constructed four models for recognizing AD in PWEs, whether PWEs based on different combinations of features using eXtreme gradient boosting (XGboost) and evaluated these models using the five-fold cross-validation method. RESULTS: The prediction model constructed by combining the clinical, PLV, and LZC features showed the best performance, with an accuracy of 96.18%, precision of 94.29%, sensitivity of 98.33%, F1-score of 96.06%, and Area Under the Curve (AUC) of 0.96. The Fisher score ranking results displayed that the top ten features were depression, educational attainment, α_P3LZC, α_T6-PzPLV, α_F7LZC, ß_Fp2-O1PLV, θ_T4-CzPLV, θ_F7-PzPLV, α_Fp2LZC, and θ_T4-PzPLV. CONCLUSIONS: The model, constructed by combining the clinical and qEEG features PLV and LZC, efficiently identified the presence of AD comorbidity in PWEs and might have the potential to complement the clinical diagnosis. Our findings suggest that LZC features in the α band and PLV features in Fp2-O1 may be potential biomarkers for diagnosing AD in PWEs.

A lattice model based on percolation theory for cold atmospheric DBD plasma decontamination kinetics.

The tailing phenomenon, where the survival curve of bacteria shows a slow tailing period after a rapid decline, is a ubiquitous inactivation kinetics process in the advanced plasma sterilization field. While classical models suggest that bacterial resistance dispersion causes the tailing phenomenon, experiments suggest that the non-uniform spatial distribution of spores (clustered structure) is the cause. However, no existing inactivation kinetics model can accurately describe spatial heterogeneity. In this paper, we propose a lattice model based on percolation theory to explain the inactivation kinetics by considering the non-uniform spatial distribution of spores and plasma. Our model divides spores into non-clustered and clustered types and distinguishes between short-tailing and long-tailing compositions and their formation mechanisms. By systematically studying the effects of different spore and plasma parameters on the tailing phenomenon, we provide a reasonable explanation for the kinetic law of the plasma sterilization survival curve and the mechanism of the tailing phenomenon in various cases. As an example, our model accurately explains the 80-second kinetics of atmospheric pressure plasma inactivation of spores, a process that previous models struggled to understand due to its multi-stage and long-tail phenomena. Our model predicts that increasing the spatial distribution probability of plasma can shorten the complete killing time under the same total energy, and we validate this prediction through experiments. Our model successfully explains the seemingly irregular plasma sterilization survival curve and deepens our understanding of the tailing phenomenon in plasma sterilization. This study offers valuable insights for the sterilization of food surfaces using plasma technology, and could serve as a guide for practical applications.

A model for the diagnosis of anxiety in patients with epilepsy based on phase locking value and Lempel-Ziv complexity features of the electroencephalogram.

OBJECTIVE: Anxiety disorders (AD) are critical factors that significantly (about one-fifth) impact the quality of life (QoL) in patients with epilepsy (PWE). Objective diagnostic methods have contributed to the identification of PWE susceptible to AD. This study aimed to identify AD in PWE by constructing a diagnostic model based on the phase locking value (PLV) and Lempel-Ziv Complexity (LZC) features of the electroencephalogram (EEG). METHODS: EEG data from 131 patients with epilepsy (PWE) were enrolled in this study. Patients were divided into two groups, anxiety disorder (AD, n = 61) and non-anxiety disorder (NAD, n = 70), according to the Hamilton Rating Scale for Anxiety (HAM-A). Support vector machine (SVM) and K-Nearest-Neighbor(KNN) algorithms were used to construct three models - the PLVEEG, LZCEEG, and PLVEEG + LZCEEG feature models. Finally, the area under the receiver operating characteristic curve (AUC) and statistical analyses were performed to evaluate the model performance. RESULTS: The efficiency of the KNN-based PLCEEG + LZCEEG feature model was the best, and the accuracy, precision, recall, F1-score, and AUC of the model after five-fold cross-validations scores were 87.89 %, 82.27 %, 98.33 %, 88.95 %, and 0.89, respectively. When the model efficiency was optimal, 29 EEG features were suggested. Further analysis of these features indicated 22 EEG features that were significantly different between the two groups, including 50 % features of the alpha (α)-band. CONCLUSIONS: The PLVEEG + LZCEEG model features can identify AD in PWE. The PLVEEG and LZCEEG characteristics of the α-band may further be explored as potential biomarkers for AD in PWE.

Exploring the effect of region on diversity and composition of weed seedbanks in herbicide-resistant crop systems in the United States.

BACKGROUND: Soil seedbanks have been recognized as one of the crucial components of agricultural ecosystems. However, studies on the shift in structure and biodiversity of soil seedbanks in herbicide-resistant crop systems are limited, and a functional trait perspective of the soil seedbank is often overlooked. RESULTS: A 6 years experiment was conducted to investigate the roles of region, crop system, and weed management strategy on species richness, functional trait diversity, and composition of the weed seedbank. Species richness was different across the interaction of region and crop system, while functional trait diversity only showed difference across regions. Species and functional trait compositions were affected by the interaction of region and crop system. Specifically, the compositional difference among crop systems was mainly determined by the significant heterogeneity of group dispersion. CONCLUSION: Growers and practitioners should consider weed functional traits in developing lasting agricultural management strategies. Long-term weed research should draw attention to the impact of transgenic crop systems and specific management tactics on weed dispersal, functional composition, and resistance evolution of weed species in such agroecosystems. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Preparation, characterization and immune response of chitosan­gold loaded Myricaria germanica polysaccharide.

In this study, a novel nano-drug delivery system (CS-Au NPs) based on gold nanoparticles (Au NPs) and chitosan (CS) that modified Myricaria germanica polysaccharide (MGP) was developed to enhance immune responses. At a MGP to CS Au ratio of 5:1, CS-Au-MGP NPs had a loading capacity of 78.27 %. The structure of CS-Au-MGP NPs were characterized by Transmission electron microscope, TEM-energy dispersive spectroscopy mapping, Fourier transform infrared spectroscopy, X-ray photoelectron spectrometer, particle size and zeta-potential distribution analysis. Under weakly acidic conditions, in vitro CS-Au-MGP NPs release was most effective. In vivo showed that co-immunization with CS-Au-MGP NPs and PCV2 significantly increased the organ index of the thymus, spleen, and liver in mice. Additionally, CS-Au-MGP NPs significantly increased the levels of IgG, IgG1, and IgG2a antibodies, as well as IFN-γ and IL-6 levels. Furthermore, the CS-Au-MGP NPs promoted proliferation of spleen T and B lymphocytes, increased the number of CD3+, CD4+, and CD8+ cells, and increased the CD4+/CD8+ T cell ratio. Meanwhile, CS-Au-MGP NPs remarkably TLR2/IRAK4 pathway activation and mRNA levels of cytokines (IFN-γ and IL-6). These results indicated that CS-Au-MGP NPs could enhance the immune activity, and it could be potentially used as an MGP delivery system for the induction of strong immune responses.

Protein arginine methylation in viral infection and antiviral immunity.

Protein arginine methyltransferase (PRMT)-mediated arginine methylation is an important post-transcriptional modification that regulates various cellular processes including epigenetic gene regulation, genome stability maintenance, RNA metabolism, and stress-responsive signal transduction. The varying substrates and biological functions of arginine methylation in cancer and neurological diseases have been extensively discussed, providing a rationale for targeting PRMTs in clinical applications. An increasing number of studies have demonstrated an interplay between arginine methylation and viral infections. PRMTs have been found to methylate and regulate several host cell proteins and different functional types of viral proteins, such as viral capsids, mRNA exporters, transcription factors, and latency regulators. This modulation affects their activity, subcellular localization, protein-nucleic acid and protein-protein interactions, ultimately impacting their roles in various virus-associated processes. In this review, we discuss the classification, structure, and regulation of PRMTs and their pleiotropic biological functions through the methylation of histones and non-histones. Additionally, we summarize the broad spectrum of PRMT substrates and explore their intricate effects on various viral infection processes and antiviral innate immunity. Thus, comprehending the regulation of arginine methylation provides a critical foundation for understanding the pathogenesis of viral diseases and uncovering opportunities for antiviral therapy.

Design of biodegradable polyurethanes and post-modification with long alkyl chains via inhibiting biofilm formation and killing drug-resistant bacteria for the treatment of wound bacterial infection.

The development of cationic polymers that simulate antimicrobial peptides to treat bacterial infections has received much research interest. In order to obtain polymers that can not only eradicate bacteria but also inhibit biofilm formation, without inducing bacterial drug resistance, a series of cationic polymers have been developed. Despite recent progress, the chemical structures of these polymers are stable, making them recalcitrant to biodegradation and metabolism within organisms, potentially inducing long-term toxicity. To overcome this limitation, herein, a novel strategy of designing biodegradable polyurethanes with tertiary amines and quaternary ammonium salts via condensation polymerization and post-functionalizing them is reported. These polymers were found to exhibit potent antibacterial activity against Staphylococcus aureus and Escherichia coli, effectively prevent the formation of Staphylococcus aureus biofilms, act quickly and effectively against bacteria and display no resistance after repeated use. In addition, the potent in vivo antibacterial effects of these antimicrobial polyurethanes in a mouse model with methicillin-resistant Staphylococcus aureus skin infection are demonstrated.

Unraveling the synergistic effects of Cu-Ag tandem catalysts during electrochemical CO2 reduction using nanofocused X-ray probes.

Controlling the selectivity of the electrocatalytic reduction of carbon dioxide into value-added chemicals continues to be a major challenge. Bulk and surface lattice strain in nanostructured electrocatalysts affect catalytic activity and selectivity. Here, we unravel the complex dynamics of synergistic lattice strain and stability effects of Cu-Ag tandem catalysts through a previously unexplored combination of in situ nanofocused X-ray absorption spectroscopy and Bragg coherent diffraction imaging. Three-dimensional strain maps reveal the lattice dynamics inside individual nanoparticles as a function of applied potential and product yields. Dynamic relations between strain, redox state, catalytic activity and selectivity are derived. Moderate Ag contents effectively reduce the competing evolution of H2 and, concomitantly, lead to an enhanced corrosion stability. Findings from this study evidence the power of advanced nanofocused spectroscopy techniques to provide new insights into the chemistry and structure of nanostructured catalysts.

Dual-mode transfer response based on electrochemical and fluorescence signals for the detection of amyloid-beta oligomers (AßO).

An aptamer sensor has been developed utilizing a dual-mode and stimuli-responsive strategy for quantitative detection of AßO (amyloid-beta oligomers) through simultaneous electrochemical and fluorescence detection. To achieve this, we employed UIO-66-NH2 as a carrier container to load MB (Methylene Blue), and Fe3O4 MNPs (iron oxide magnetic nanoparticles) with aptamer (ssDNA-Fe3O4 MNPs) fixed on their surface for biological gating. The ssDNA-Fe3O4 MNPs were immobilized onto the surface of UIO-66-NH2 through hydrogen bonding between the aptamer and the -NH2 group on the surface of UIO-66-NH2, thereby encapsulating MB and forming ssDNA-Fe3O4@MB@UIO-66-NH2. During the detection of AßO, the aptamer selectively reacted with AßO to form the AßO-ssDNA-Fe3O4 complex, leading to its detachment from the surface of UIO-66-NH2. This detachment facilitated the release of MB, enabling its electrochemical detection. Simultaneously, the AßO-ssDNA-Fe3O4 complex was efficiently collected and separated using a magnet after leaving the container's surface. Furthermore, the addition of NaOH facilitated the disconnection of biotin modifications at the 3' end of the aptamer from the avidin modifications on the Fe3O4 MNPs. Consequently, the aptamer detached from the surface of Fe3O4 MNPs, resulting in the restoration of fluorescence intensity of FAM (fluorescein-5'-carboxamidite) modified at its 5' end for fluorescence detection. The dual-mode sensor exhibited significantly enhanced differential pulse voltammetry signals and fluorescence intensity compared to those in the absence of AßO. The sensor demonstrated a wide detection range of 10 fM to 10 µM, with a detection limit of 3.4 fM. It displayed excellent performance in detecting actual samples and holds promising prospects for early diagnosis of Alzheimer's disease.

Acute toxicological evaluation of AT-533 and AT-533 gel in Sprague-Dawley rats.

BACKGROUND: AT-533 is a novel heat shock protein 90 inhibitor that exerting anti-inflammatory, antiviral, and antitumor efficacy. Furthermore, the gel made of AT-533 as raw material named AT-533 gel has the function of repairing keratitis and dermatitis caused by herpes virus infection. However, the acute safety evaluation of AT-533 and AT-533 gel has not been conducted. METHODS AND RESULTS: Herein, we performed acute toxicological studies of AT-533 and AT-533 gel in Sprague-Dawley rats. Fifteen-day acute toxicity study of AT-533 was conducted in both male and female Sprague-Dawley rats at doses of 5, 50, 250 and 500 mg/kg and AT-533 gel at 5 g/kg in the study. During experiment, food consumption and mortality were observed and body weight, hematology, serum biochemistry and histopathological assessment of rats were carried out. No abnormal changes were observed in rats percutaneously treated with AT-533 at 5 mg/kg and 50 mg/kg and AT-533 gel. However, loss of appetite and body weight, adverse reactions, toxicologically relevant alterations in hematology and biochemistry were found in rats percutaneously treated with AT-533 at 250 mg/kg and 500 mg/kg during 15-day acute dermic toxicity study. CONCLUSIONS: The aforementioned results suggested that the LD50 of AT-533 is 228.382 mg/kg and the LD50 of AT-533 gel is greater than 5 g/kg. These findings indicated that AT-533 is non-toxic in rats when the dose less than 50 mg/kg and AT-533 gel can be considered a gel with no toxicity at doses less than 5 g/kg.

Activity-guided isolation and identification of antiherpesvirus and antineuroinflammatory active terpenoids from Artemisia vulgaris L. based on the LC-MS/MS molecular network.

Seven undescribed terpenoids, comprising two guaiane-type sesquiterpene lactones (1-2), one eucalyptol-type sesquiterpene (3), one monolactone (4), and three triterpenoids (5-7), along with 35 known analogues, were isolated from the leaves of Artemisia vulgaris L. Their structures and configurations were analysed by extensive spectroscopy. Compounds 1, 2, 8-10, 13, 17, 19, and 28 showed antineuroinflammatory activity, and compounds 1 and 2 revealed remarkable antineuroinflammatory effects, with an IC50 value of 2.2 ± 0.1 and 1.6 ± 0.1 µM, more potent than the positive control drug dexamethasone. Furthermore, compounds 1 and 2 could inhibit the expression of BV-2 inflammatory genes (IL-6, TNF-α, IL-1ß) induced by LPS, downregulate the critical inflammatory protein production of iNOS and COX-2. The anti-HSV-1 activity screening revealed that compounds 28, 29 and 38 exhibited inhibitory activity against HSV-1 proliferation. Particularly, compound 28 exhibited a significant anti-HSV-1 effect, inhibiting the proliferation of HSV-1 and acyclovir-resistant strains of HSV-1/153 and HSV-1/Blue. Our research identified compounds 1, 2, and 28 from A. vulgaris., which could potentially serve as lead compounds for antineuroinflammatory and anti-HSV-1 activities.

Luteolin inhibits herpes simplex virus 1 infection by activating cyclic guanosine monophosphate-adenosine monophosphate synthase-mediated antiviral innate immunity.

BACKGROUND: The successive outbreaks of large-scale infectious diseases due to virus infection have been a major threat to human health in recent decades. Herpes simplex virus I (HSV-1) is a widely-disseminated DNA virus that infects the central nervous system to cause herpes labialis, keratitis and herpes simplex virus encephalitis (HSE), resulting in recurrent lifelong clinical or subclinical episodes. Luteolin is a plant flavone that has been extensively used in the treatment of various human diseases, including carcinogenesis, inflammation and chronic degenerative diseases. PURPOSE: The aim of this study was to investigate the antiviral molecular mechanism of luteolin against HSV-1 infection in vitro and in vivo. METHODS: The antiviral effect of luteolin in cell lines was examined by viral plaque assay, RT-qPCR, Western blot and time-of-addition assay. The interaction between luteolin and cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) was evaluated by molecular modeling and semi-denaturing detergent agarose gel electrophoresis. The efficacy of luteolin on HSE was evaluated in the HSE mouse model by analyzing weight loss, neurodegenerative symptoms and histopathological scores. Cytokine expression and protein levels were examined by RT-qPCR, Western blot and ELISA. RESULTS: Luteolin inhibited the early process of HSV-1 infection, without affecting the infection of acyclovir-resistant HSV-1 strains. In addition, luteolin enhanced antiviral type I interferon production and activated the cytoplasmic DNA-sensing cGAS-stimulator of interferon gene (STING) pathway. Luteolin directly bound the active substrate binding site and promoted the oligomerization of cGAS. Luteolin also inhibited HSE-related weight loss, neurodegeneration and neuroinflammation in mice caused by HSV-1 infection. Furthermore, luteolin enhanced type I interferon expression and stimulated the cGAS-STING signaling pathway in vivo. CONCLUSION: Luteolin inhibited the post-entry process of HSV-1 by activating the cGAS-STING pathway to promote antiviral interferon production. These results provided the rationale for luteolin as a potent cGAS activator and antiviral agent.

Delayed 18F-FDG PET imaging provides better metabolic asymmetry in potential epileptogenic zone in temporal lobe epilepsy.

Objective: To investigate the value of 18F-FDG positron emission tomography/computed tomography (PET/CT) two time point imaging for the identification of the potential epileptogenic zone (EZ) in temporal lobe epilepsy (TLE). Methods: Fifty-two patients with TLE were prospectively enrolled in the 18F-FDG PET/CT two time point imaging study. The early imaging was obtained approximately 40 min (43.44 ± 18.04 min) after 18F-FDG injection, and the delayed imaging was obtained about 2 to 3 h (160.46 ± 28.70 min) after the injection. Visual and semi-quantitative analysis of 18F-FDG uptake were performed at the two time points in EZ and contralateral symmetrical region. The mean standardized uptake value (SUVmean) of EZ and contralateral symmetrical region was calculated to determine the asymmetry index (AI) of the early and delayed images, as well as in the MRI positive and negative patient groups. Results: Semi-quantitative analysis demonstrated that AI of the early and delayed 18F-FDG PET/CT images was 13.47 ± 6.10 and 16.43 ± 6.66, respectively. The ΔAI was 2.95 ± 3.05 in 52 TLE patients between the two time points. The AI of the EZ was significantly elevated in delayed images compared to the early images (p < 0.001). The AI of delayed imaging was also significantly elevated compared to the early imaging in both MRI positive (ΔAI = 2.81 ± 2.54, p < 0.001) and MRI negative (ΔAI = 3.21 ± 3.91, p < 0.003) groups, and more pronounced in MRI negative group. Visual analysis also showed that the delayed imaging appeared to be superior to the early imaging for identification of potential EZ. Conclusion: Delayed 18F-FDG PET imaging provided significantly better than the early imaging in the identification of potential EZ, which can be valuable during epilepsy pre-surgical evaluation in patients with TLE.

Automatic recognition of cephalometric landmarks via multi-scale sampling strategy.

The identification of head landmarks in cephalometric analysis significantly contributes in the anatomical localization of maxillofacial tissues for orthodontic and orthognathic surgery. However, the existing methods face the limitations of low accuracy and cumbersome identification process. In this pursuit, the present study proposed an automatic target recognition algorithm called Multi-Scale YOLOV3 (MS-YOLOV3) for the detection of cephalometric landmarks. It was characterized by multi-scale sampling strategies for shallow and deep features at varied resolutions, and especially contained the module of spatial pyramid pooling (SPP) for highest resolution. The proposed method was quantitatively and qualitatively compared with the classical YOLOV3 algorithm on the two data sets of public lateral cephalograms, undisclosed anterior-posterior (AP) cephalograms, respectively, for evaluating the performance. The proposed MS-YOLOV3 algorithm showed better robustness with successful detection rates (SDR) of 80.84% within 2 mm, 93.75% within 3 mm, and 98.14% within 4 mm for lateral cephalograms, and 85.75% within 2 mm, 92.87% within 3 mm, and 96.66% within 4 mm for AP cephalograms, respectively. It was concluded that the proposed model could be robustly used to label the cephalometric landmarks on both lateral and AP cephalograms for the clinical application in orthodontic and orthognathic surgery.