Tandemly expanded OR17b in Himalaya ghost moth facilitates larval food allocation via olfactory reception of plant-derived tricosane.

Herbivorous insects utilize intricate olfactory mechanisms to locate food plants. The chemical communication of insect-plant in primitive lineage offers insights into evolutionary milestones of divergent olfactory modalities. Here, we focus on a system endemic to the Qinghai-Tibetan Plateau to unravel the chemical and molecular basis of food preference in ancestral Lepidoptera. We conducted volatile profiling, neural electrophysiology, and chemotaxis assays with a panel of host plant organs to identify attractants for Himalaya ghost moth Thitarodes xiaojinensis larvae, the primitive host of medicinal Ophiocordyceps sinensis fungus. Using a DREAM approach based on odorant induced transcriptomes and subsequent deorphanization tests, we elucidated the odorant receptors responsible for coding bioactive volatiles. Contrary to allocation signals in most plant-feeding insects, T. xiaojinensis larvae utilize tricosane from the bulbil as the main attractant for locating native host plant. We deorphanized a TxiaOR17b, an indispensable odorant receptor resulting from tandem duplication of OR17, for transducing olfactory signals in response to tricosane. The discovery of this ligand-receptor pair suggests a survival strategy based on food location via olfaction in ancestral Lepidoptera, which synchronizes both plant asexual reproduction and peak hatch periods of insect larvae.

Revolutionizing Medicinal Chemistry: The Application of Artificial Intelligence (AI) in Early Drug Discovery.

Artificial intelligence (AI) has permeated various sectors, including the pharmaceutical industry and research, where it has been utilized to efficiently identify new chemical entities with desirable properties. The application of AI algorithms to drug discovery presents both remarkable opportunities and challenges. This review article focuses on the transformative role of AI in medicinal chemistry. We delve into the applications of machine learning and deep learning techniques in drug screening and design, discussing their potential to expedite the early drug discovery process. In particular, we provide a comprehensive overview of the use of AI algorithms in predicting protein structures, drug-target interactions, and molecular properties such as drug toxicity. While AI has accelerated the drug discovery process, data quality issues and technological constraints remain challenges. Nonetheless, new relationships and methods have been unveiled, demonstrating AI's expanding potential in predicting and understanding drug interactions and properties. For its full potential to be realized, interdisciplinary collaboration is essential. This review underscores AI's growing influence on the future trajectory of medicinal chemistry and stresses the importance of ongoing synergies between computational and domain experts.

Identification of a Non-Nucleoside Reverse Transcriptase Inhibitor against Human Immunodeficiency Virus-1.

The HIV-1 infection epidemic remains a global health problem. Current antiretroviral treatments are effective in controlling the progression of a severe infection. However, the emergence of drug resistance requires an urgent identification of new treatment regimes. HIV-1 reverse transcriptase (RTs) has been a successful therapeutic target owing to its high specificity and potent antiviral properties; therefore, it has become an essential component of current HIV-1 standard treatments. This study identified a new HIV-1 RTs inhibitor (Compound #8) that is structurally unique and greatly effective against HIV-1 through chemical library screening and a medicinal chemistry program by analyzing the structure-activity relationship (SAR). Further analysis of molecular docking and mechanisms of action demonstrated that Compound #8 is a novel type of HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) with a flexible binding mode. Therefore, it exhibits great therapeutic potential when combined with other existing HIV-1 drugs. Our current studies suggest that Compound #8 is a promising novel scaffold for the development of new HIV-1 treatments.

Systematic analyses of the sequence conservation and ligand interaction patterns of purinergic P1 and P2Y receptors provide a structural basis for receptor selectivity.

Purinergic receptors are membrane proteins that regulate numerous cellular functions by catalyzing reactions involving purine nucleotides or nucleosides. Among the three receptor families, i.e., P1, P2X, and P2Y, the P1 and P2Y receptors share common structural features of class A GPCR. Comprehensive sequence and structural analysis revealed that the P1 and P2Y receptors belong to two distinct groups. They exhibit different ligand-binding site features that can distinguish between specific activators. These specific amino acid residues in the binding cavity may be involved in the selectivity and unique pharmacological behavior of each subtype. In this study, we conducted a structure-based analysis of purinergic P1 and P2Y receptors to identify their evolutionary signature and obtain structural insights into ligand recognition and selectivity. The structural features of the P1 and P2Y receptor classes were compared based on sequence conservation and ligand interaction patterns. Orthologous protein sequences were collected for the P1 and P2Y receptors, and sequence conservation was calculated based on Shannon entropy to identify highly conserved residues. To analyze the ligand interaction patterns, we performed docking studies on the P1 and P2Y receptors using known ligand information extracted from the ChEMBL database. We analyzed how the conserved residues are related to ligand-binding sites and how the key interacting residues differ between P1 and P2Y receptors, or between agonists and antagonists. We extracted new similarities and differences between the receptor subtypes, and the results can be used for designing new ligands by predicting hotspot residues that are important for functional selectivity.

A ten-year surgical experience in patients of Tessier No.0 cleft with a bifid nose.

BACKGROUND: Tessier No.0 cleft with a bifid nose is a rare malformation. Reconstruction of the nose is essential for children/adults to correct facial cosmetic defects and contribute to developing patients' mental health. The aim of the study was to present the 10-year clinical results using local flaps or expanded forehead flaps in bifid nose patients. METHODS: A retrospective review was performed between January of 2010 and August of 2021 in our department. Sex, age at surgery, associated anomalies, and type of operation were reviewed. RESULTS: A total of 33 patients were retained. The median duration of follow-up was 5.5 years. Fourteen patients underwent multi-stage nasal reconstruction using expanded forehead flap with costal cartilage as a framework, and 16 patients were operated with local skin flap with silicone while the other three were operated with local skin flap with costal cartilage. There were six cases (18.18%) of complications in our study. During follow-up, 28 patients (84.85%) had satisfactory outcomes, four patients (12.12%) had partially satisfactory results, and one patient (3.03%) had an unsatisfactory outcome. CONCLUSION: Using local skin flap with silicone or costal cartilage rhinoplasty and nasal reconstruction using expanded forehead flap with costal cartilage for patients with a bifid nose of Tessier No.0 cleft showed that it was safe and effective, and had satisfying results in the long-term follow-up.

Mediating a host cell signaling pathway linked to overwinter mortality offers a promising therapeutic approach for improving bee health.

INTRODUCTION: Honey bees provides valuable pollination services for world food crops and wild flowering plants which are habitats of many animal species and remove carbon dioxide from the atmosphere, a powerful tool in the fight against climate change. Nevertheless, the honey bee population has been declining and the majority of colony losses occur during the winter. OBJECTIVES: The goal of this study was to understand the mechanisms underlying overwinter colony losses and develop novel therapeutic strategies for improving bee health. METHODS: First, pathogen prevalence in overwintering bees were screened between 2015 and 2018. Second, RNA sequencing (RNA-Seq) for transcriptional profiling of overwintering honey bees was conducted and qRT-PCR was performed to confirm the results of the differential expression of selected genes. Lastly, laboratory bioassays were conducted to measure the effects of cold challenges on bee survivorship and stress responses and to assess the effect of a novel medication for alleviating cold stress in honey bees. RESULTS: We identified that sirtuin signaling pathway is the most significantly enriched pathway among the down-regulated differentially expressed genes (DEGs) in overwintering diseased bees. Moreover, we showed that the expression of SIRT1 gene, a major sirtuin that regulates energy and immune metabolism, was significantly downregulated in bees merely exposed to cold challenges, linking cold stress with altered gene expression of SIRT1. Furthermore, we demonstrated that activation of SIRT1 gene expression by SRT1720, an activator of SIRT1 expression, could improve the physiology and extend the lifespan of cold-stressed bees. CONCLUSION: Our study suggests that increased energy consumption of overwintering bees for maintaining hive temperature reduces the allocation of energy toward immune functions, thus making the overwintering bees more susceptible to disease infections and leading to high winter colony losses. The novel information gained from this study provides a promising avenue for the development of therapeutic strategies for mitigating colony losses, both overwinter and annually.

A novel volatile deterrent from symbiotic bacteria of entomopathogenic nematodes fortifies field performances of nematodes against fall armyworm larvae.

The core elements of entomopathogenic nematode toxicity towards the fall armyworm Spodoptera frugiperda are associated with symbiotic bacteria. These microbes provide independent control effects and are reported to have repellency to insect pests. However, the ecological background of this nematode-bacteria-insect communication module is elusive. This work aims to identify key chemical cues which drive the trophic interactions through olfactory reception of S. frugiperda, and to inspire implementations with these isolated behavioral regulators in the corn field. A total of 657 volatiles were found within 13 symbiotic bacterial strains, and five of them induced significant electrophysiological responses of S. frugiperda larvae. 2-Hexynoic acid was demonstrated to exhibit a dominant role in deterring S. frugiperda larvae from feeding and localization. Field implementations with this novel volatile deterrent have resulted in fortified nematode applications. 2-Hexynoic acid acts as an excellent novel deterrent and presents remarkable application potential against fall armyworm larvae. Emissions from symbiotic bacteria of entomopathogenic nematodes are key players in chemical communication among insects, nematodes, and microbes. The olfactory perceptions and molecular targets for this volatile are worthy of future research.

Flexible, disposable photocatalytic plastic films for the destruction of viruses.

A thin, 30 µm, flexible, robust low-density polyethylene, LDPE, film, loaded with 30 wt% P25 TiO2, is extruded and subsequently rendered highly active photocatalytically by exposing it to UVA (352 nm, 1.5 mW cm-2) for 144 h. The film was tested for anti-viral activity using four different viruses, namely, two strains of Influenza A Virus (IAV), WSN, and a recombinant PR8, encephalomyocarditis virus (EMCV), and SARS-CoV-2 (SARS2). The film was irradiated with either UVA radiation (352 nm, 1.5 mW cm-2; although only 0.25 mW cm-2 for SARS2) or with light from a cool white fluorescent lamp (UVA irradiance: 365 nm, 0.047 mW cm-2). In all cases the films exhibited an average virus inactivation rate of >1.5log/h. In the case of SARS2, the rates were > 2log/h, with the rate determined using a dedicated, low intensity UVA source (0.25 mW cm-2) only 1.3 x's faster than that for a cool white lamp (UVA irradiance = 0.047 mW cm-2), which suggests that SARS2 is particularly prone to photocatalytic inactivation even under low UV irradiation conditions, such as found in a room lit with just white fluorescent tubes. This is the first example of a flexible, very thin, photocatalytic plastic film, produced by a scalable process (extrusion), for virus inactivation. The potential of such a film for use as a disposable, self-sterilising thin plastic material alternative to the common, non-photocatalytic, inert equivalent used currently for curtains, aprons and table coverings in healthcare is discussed briefly.

Establishment of a patient-derived organoid model and living biobank for nasopharyngeal carcinoma.

Background: Recurrent nasopharyngeal carcinoma (NPC) remains a major challenge for clinicians and scientists. Tumor organoid is a revelational disease model that highly resembled the heterogeneity and histopathological characteristics of original tumors. This study aimed to optimize the modeling process of patient-derived NPC organoids (NPCOs), and establish a living-biobank of NPCs to study the mechanism and explore the more effective treatment of the disease. Methods: Sixty-two fresh NPC tissue samples and 15 normal mucosa samples were collected for 3-dimensional (3D) organoid culture. The organoids were confirmed using hematoxylin and eosin assays. The expression levels of CD133, CD44, BMI-1, and Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) were detected by immunohistochemistry (IHC) and in situ hybridization (ISH). Recurrent NPCOs were frozen in liquid nitrogen for 6 months and then resuscitated and passaged. Results: We identified a novel two-step enzymatic strategy for the treatment of NPC and nasal mucosa specimens and an optimal medium for culturing NPCOs and nasal mucosa organoids (NMOs). Organoid cultures were generated from 34 primary NPC samples, 28 recurrent NPC samples, and 15 normal mucosa samples. The success rates for primary NPCO, recurrent NPCO, and NMO formation were 47.06%, 81.25%, and 86.5%, respectively. All the NPCOs were EBER positive and CK7 negative. Recurrent NPCOs had higher expressions of stem cell markers, including BMI-1, CD44, and CD133. Additionally, recurrent NPCOs could be cultured to passage 4 and frozen and revived repeatedly, while primary NPCOs were challenging to culture. Conclusions: In summary, we successfully established a living biobank using the NPCO model, which has enormous potential in basic and clinical research on NPC.

Development of a nomogram for severe costal cartilage calcification: a cohort study.

BACKGROUND: There was few research on the causes or factors of costal cartilage calcification. Thus, this study aimed to develop a nomogram to predict the possibility of severe costal cartilage calcification. METHODS: The cohort study included 882 patients who underwent computed tomographic (CT) scan of the chest with three-dimensional reconstructions and have completed the questionnaire between June 2020 to October 2021. The potential variables were included age, sex, body mass index (BMI), nation, residence, smoking, drinking, bedtime, exercise, self-pressure, the frequencies of milk, yogurt, carbonated drink, meat, fish, sea food, fruits intake, hypertension, diabetes, thyroid or parathyroid disease and osteoarthritis. We used the least absolute shrinkage and selection operator (LASSO) regression model to identify the optimal predictive features. Multivariable logistic regression analysis was used to build the predicting model. The receiver operating characteristic (ROC) curve and concordance index (C-index) were used to evaluate the accuracy of the nomogram. Moreover, decision curve analysis (DCA) was to estimate the clinical usefulness of the nomogram. Finally, we adopted internal validation of enhanced bootstrap adjustment for optimism to predict the C-index of the model. RESULTS: The predictive nomogram contained 11 clinical features using LASSO regression, and "Sex" and "Age" were the most important factor due to the most significant proportion. The model showed good discrimination with a C-index of 0.805, and the internal validation was 0.735. DCA (the threshold probability of a patient is 1-77%) and the ROC curve [the area under ROC (AUC) was 0.805, and the sensitivity and specificity were 0.647 and 0.894] demonstrated that the nomogram was possibly clinically helpful. CONCLUSIONS: This is the first study to develop a nomogram to predict severe costal cartilage. Use of this nomogram might help patients prevent calcification by changing living habits.

A Novel Early Warning Model for Hand, Foot and Mouth Disease Prediction Based on a Graph Convolutional Network.

Objectives: Hand, foot and mouth disease (HFMD) is a widespread infectious disease that causes a significant disease burden on society. To achieve early intervention and to prevent outbreaks of disease, we propose a novel warning model that can accurately predict the incidence of HFMD. Methods: We propose a spatial-temporal graph convolutional network (STGCN) that combines spatial factors for surrounding cities with historical incidence over a certain time period to predict the future occurrence of HFMD in Guangdong and Shandong between 2011 and 2019. The 2011-2018 data served as the training and verification set, while data from 2019 served as the prediction set. Six important parameters were selected and verified in this model and the deviation was displayed by the root mean square error and the mean absolute error. Results: As the first application using a STGCN for disease forecasting, we succeeded in accurately predicting the incidence of HFMD over a 12-week period at the prefecture level, especially for cities of significant concern. Conclusions: This model provides a novel approach for infectious disease prediction and may help health administrative departments implement effective control measures up to 3 months in advance, which may significantly reduce the morbidity associated with HFMD in the future.

A Modified Large-Cap Graft in East Asian Revision Rhinoplasty.

BACKGROUND: Reconstructing a well-defined nasal tip is a big challenge for East Asian patients, especially with nasal tip irregularities or short noses in revision rhinoplasty. This study aims to report our experience with a modified large-cap graft for improving the contour of the nasal tip in revision rhinoplasty. METHODS: A retrospective review was conducted for 91 patients (81 females, 10 males; mean age, 26.8 ± 6.7 years) who underwent revision rhinoplasty with a modified large-cap graft. The rhinoplasty outcome evaluation (ROE) was used for investigating patient satisfaction. The aesthetic outcomes were assessed by preoperative and postoperative photographs by two blinded plastic surgeons using the Independent Rhinoplasty Outcome Score. RESULTS: Most patients reported satisfactory aesthetic outcomes with overall ROE score increasing from preoperative 11.66 ± 3.98 to postoperative 17.30 ± 5.03 (p < 0.001). The doctors' evaluations on the improved contour of the nose rendered an overall score of 3.77 ± 0.42. The complication rate was 3.3% (pleural tear, 1.1%; hypertrophic scar, 2.2%) at the donor site, and 7.7% at the recipient site (warping, 3.3%; extrusion, 1.1%; deviation, 2.2%; infection, 1.1%). No other complications were observed during follow-up. CONCLUSIONS: Large-cap graft may be safe and efficient for reconstructing contour of the nasal tip in revision rhinoplasty for East Asian patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

3D printed, plastic photocatalytic flow reactors for water purification.

3D printing is known as a fast, inexpensive, reproducible method for producing prototypes but is also fast becoming recognised as a scalable, advanced manufacture process. Two types of lab-scale, 3D printed plastic, fixed-film, flow-through photocatalytic reactors are described, both of which are sinusoidal in shape, and only differ in that one has no baffles, reactor A, whereas the other has, reactor B. Both reactors are lined with a P25 TiO2/polylactic acid (PLA) coating, which, after UVA pre-conditioning, is used to photocatalyse the bleaching of circulating aqueous solutions of either methylene blue, MB, or phenol, PhOH, repeatably, without any obvious loss of activity. The rate of the photocatalysed bleaching of MB exhibited by reactor B shows a much lower dependence upon flow rate than reactor A, due to the greater lateral mixing of the laminar flow streams produced by the baffles. The photonic efficiencies of reactor A for the photocatalysed bleaching of MB and PhOH were determined to be 0.025% and 0.052%, respectively, and the photocatalytic space-time yields (PSTY) to be 0.98 × 10-4 and 1.49 × 10-4 m3 of reaction solution.m-3 reactor volume.day-1.kW-1, respectively. This is the first example of an all plastic, 3D printed photocatalytic reactor and demonstrates the advantages of 3D printing for prototyping. Given the 3D printing is a scalable process, possible potential areas of application are discussed briefly.

Behavioural regulator and molecular reception of a double-edge-sword hunter beetle.

BACKGROUND: The black carabid beetle Calosoma maximoviczi is a successful predator that serves as both a beneficial insect and a severe threat to economic herbivores. Its hunting technique relies heavily on olfaction, but the underlying mechanism has not been studied. Here, we report the electrophysiological, ecological and molecular traits of bioactive components identified from a comprehensive panel of natural odorants in the beetle-prey-plant system. The aim of this work was to investigate olfactory perceptions and their influence on the behaviours of C. maximoviczi. RESULTS: Among the 200 identified volatiles, 18 were concentrated in beetle and prey samples, and 14 were concentrated in plants. Insect feeding damage to plants led to a shift in the emission fingerprint. Twelve volatiles were selected using successive electrophysiological tests. Field trials showed that significant sex differences existed when trapping with a single chemical or chemical mixture. Expression profiles indicated that sex-biased catches were related to the expression of 15 annotated CmaxOBPs and 40 CmaxORs across 12 chemosensory organs. In silico evaluations were conducted with 16 CmaxORs using modelling and docking. Better recognition was predicted for the pairs CmaxOR5-(Z)-3-hexenyl acetate, CmaxOR6-ß-caryophyllene, CmaxOR18-(E)-ß-ocimene and CmaxOR18-tetradecane, with higher binding affinity and a suitable binding pocket. Lastly, 168Y in CmaxOR6 and 142Y in CmaxOR18 were predicted as key amino acid residues for binding ß-caryophyllene and tetradecane, respectively. CONCLUSION: This work provides an example pipeline for de novo investigation in C. maximoviczi baits and the underlying olfactory perceptions. The results will benefit the future development of trapping-based integrated pest management strategies and the deorphanization of odorant receptors in ground beetles. © 2022 Society of Chemical Industry.

Characterizations of botanical attractant of Halyomorpha halys and selection of relevant deorphanization candidates via computational approach.

Halyomorpha halys has been recognized as a global cross-border pest species. Along with well-established pheromone trapping approaches, there have been many attempts to utilize botanical odorant baits for field monitoring. Due to sensitivity, ecological friendliness, and cost-effectiveness for large-scale implementation, the selection of botanical volatiles as luring ingredients and/or synergists for H. halys is needed. In the current work, botanical volatiles were tested by olfactometer and electrophysiological tests. Results showed that linalool oxide was a potential candidate for application as a behavioral modifying chemical. It drove remarkable attractiveness toward H. halys adults in Y-tube assays, as well as eliciting robust electroantennographic responsiveness towards antennae. A computational pipeline was carried out to screen olfactory proteins related to the reception of linalool oxide. Simulated docking activities of four H. halys odorant receptors and two odorant binding proteins to linalool oxide and nerolidol were performed. Results showed that all tested olfactory genes were likely to be involved in plant volatile-sensing pathways, and they tuned broadly to tested components. The current work provides insights into the later development of field demonstration strategies using linalool oxide and its molecular targets.

Diced Cartilage Techniques in Rhinoplasty.

Diced cartilage has been widely applied in rhinoplasty, especially for segmental dorsal augmentation, with favorable outcomes over time. Various techniques were developed to increase both stability and viability of diced cartilage, including wrappings with non-blood material/blood products and changing the shapes of the diced cartilage, while the optimal technique is inconclusive. This article systematically reviews the current strategies of diced cartilage technique for rhinoplasty in the databases and emphasizes different wrapping materials. Free diced cartilage has a potential risk of gathering in certain regions and causing postoperative irregularities. Among non-blood wrapping materials, Surgicel is now rarely used due to severe foreign body reactions. The obvious drawbacks of fascia are donor site morbidity, inadequate quantity, and time-consuming. Although diced cartilage wrapped in tutoplast-processed fascia lata, AlloDerm, or esterified hyaluronic acid has achieved primary encouraging results, the increased inflammation raised controversies regarding their clinical use. Diced cartilage wrapped with blood products, such as platelet-rich fibrin or concentrated growth factor, achieved long-term reliable aesthetic results, and shaved cartilage and ultra-diced cartilage have recently shown satisfactory clinical outcomes, while further study is still needed. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Paranasal Augmentation Using Diced Costal Cartilage for Midface Concavity: A Retrospective Study of 68 Patients.

BACKGROUND: Paranasal augmentation was effective management for midface concavity. Both alloplastic graft (e.g. silicone, porous polyethylene, or expanded polytetrafluorethylene) and autologous tissue (e.g. costal cartilage) were used for paranasal augmentation. The study aims to evaluate the safety and efficacy of paranasal augmentation using diced costal cartilage for midface concavity. METHODS: A retrospective review of demographic data and complications was conducted for consecutive patients who underwent paranasal augmentation using diced costal cartilage. A questionnaire was used for investigating the patient's satisfaction (i.e. overall satisfaction, bilateral alar bases symmetry, improvement of concavity, and foreign body sensation). Patients' photographs were used to evaluate aesthetic outcomes (i.e. overall satisfaction, bilateral alar bases symmetry, and improvement of concavity) by third-party doctors. RESULTS: Sixty-eight patients (60 females; mean age, 27.1 ± 8.2 years) were included. During a median follow-up of 6.5 months, costal cartilage migration occurred in 13 (19.1%) patients and partial resorption occurred in 2 (2.9%) patients. Seventy-five per cent of the patients and 98.5% of the doctors reported overall satisfaction. Bilateral alar bases asymmetry by 20 (29.4%) patients, no improvement of concavity by 13 (19.1%) patients, and foreign body sensation by 13 (19.1%) patients were reported. While bilateral alar bases asymmetry was not reported, improvement of concavity was reported in 67 (98.5%) patients by third-party doctors. On both univariate and multivariate analyses, improvement of concavity was significantly associated with patients' overall satisfaction (p = 0.008 and 0.045, respectively), while bilateral alar bases symmetry and foreign body sensation were not (all p > 0.05). CONCLUSIONS: Paranasal augmentation using diced costal cartilage seems a safe and effective method for midface concavity. Improvement of concavity may be significantly associated with patients' overall satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Novel Early Warning Model for Hand, Foot and Mouth Disease Prediction Based on a Graph Convolutional Network / 生物医学与环境科学（英文）

Objectives@#Hand, foot and mouth disease (HFMD) is a widespread infectious disease that causes a significant disease burden on society. To achieve early intervention and to prevent outbreaks of disease, we propose a novel warning model that can accurately predict the incidence of HFMD.@*Methods@#We propose a spatial-temporal graph convolutional network (STGCN) that combines spatial factors for surrounding cities with historical incidence over a certain time period to predict the future occurrence of HFMD in Guangdong and Shandong between 2011 and 2019. The 2011-2018 data served as the training and verification set, while data from 2019 served as the prediction set. Six important parameters were selected and verified in this model and the deviation was displayed by the root mean square error and the mean absolute error.@*Results@#As the first application using a STGCN for disease forecasting, we succeeded in accurately predicting the incidence of HFMD over a 12-week period at the prefecture level, especially for cities of significant concern.@*Conclusions@#This model provides a novel approach for infectious disease prediction and may help health administrative departments implement effective control measures up to 3 months in advance, which may significantly reduce the morbidity associated with HFMD in the future.

Stage- and Rearing-Dependent Metabolomics Profiling of Ophiocordyceps sinensis and Its Pipeline Products.

Cordyceps, a parasitic complex of the fungus Ophiocordyceps sinensis (Berk.) (Hypocreales: Ophiocordycipitaceae) and the ghost moth Thitarodes (Lepidoptera: Hepialidae), is a historical ethnopharmacological commodity in China. Recently, artificial cultivation of Chinese cordyceps has been established to supplement the dwindling natural resources. However, much is unknown between the natural and cultivated products in terms of nutritional aspect, which may provide essential information for quality evaluation. The current study aims to determine the metabolic profiles of 17 treatments from 3 sample groups including O. sinensis fungus, Thitarodes insect and cordyceps complex, using Gas Chromatography - Quadrupole Time-of-Flight Mass Spectrometry. A total of 98 metabolites were detected, with 90 of them varying in concentrations among groups. The tested groups could be separated, except that fungal fruiting body was clustered into the same group as Chinese cordyceps. The main distinguishing factors for the groups studied were the 24 metabolites involved in numerous different metabolic pathways. In conclusion, metabolomics of O. sinensis and its related products were determined mainly by the fruiting bodies other than culture methods. Our results suggest that artificially cultured fruiting bodies and cordyceps may share indistinguishable metabolic functions as the natural ones.

Infection of Ophiocordyceps sinensis Fungus Causes Dramatic Changes in the Microbiota of Its Thitarodes Host.

The Chinese cordyceps is a unique and valuable parasitic complex of Thitarodes/Hepialus ghost moths and the Ophiocordyceps sinensis fungus for medicine and health foods from the Tibetan Plateau. During artificial cultivation of Chinese cordyceps, the induction of blastospores into hyphae is a prerequisite for mummification of the infected Thitarodes larvae. To explore the microbial involvement in the induction of mycelia-blastospore transition, the microbiota of the hemolymph and gut from Thitarodes xiaojinensis larvae with or without injected O. sinensis blastospores were investigated by culture-dependent and -independent methods. Twenty-five culturable bacterial species and 14 fungal species, together with 537 bacterial operational taxonomic units (OTUs) and 218 fungal OTUs, were identified from the hemolymph and gut of samples from five stages including living larvae without injected fungi (A) or with high blastospore load (B), mummifying larvae without mycelia coating (C), freshly mummifying larvae coated with mycelia (D), and completely mummified larvae with mycelia (E). Two culturable bacterial species (Serratia plymuthica, Serratia proteamaculans), and 47 bacterial and 15 fungal OTUs were considered as shared species. The uninfected larval hemolymph contained 13 culturable bacterial species but no fungal species, together with 164 bacterial and 73 fungal OTUs. To our knowledge, this is the first study to detect large bacterial communities from the hemolymph of healthy insect larvae. When the living larvae contained high blastospore load, the culturable bacterial community was sharply inhibited in the hemolymph but the bacterial and fungal community greatly increased in the gut. In general, high blastospore load increased bacterial diversity but sharply decreased fungal diversity in the hemolymph and gut by OTUs. The bacterial loads of four culturable species (Chryseobacterium sp., Pseudomonas fragi, S. plymuthica, S. proteamaculans) increased significantly and O. sinensis and Pseudomonas spp. became dominant microbes, when the infected larvae became mummified, indicating their possible involvement in the larval mummification process. The discovery of many opportunistic pathogenic bacteria in the hemolymph of the healthy larvae, the larval microbial diversity influenced by O. sinensis challenge and the involvement of dominant bacteria during larval mummification process provide new insight into the infection and mummification mechanisms of O. sinensis in its Thitarodes hosts.