Identification of the mutual gliding locus as a factor for gut colonization in non-native bee hosts using the ARTP mutagenesis.

BACKGROUND: The gut microbiota and their hosts profoundly affect each other's physiology and evolution. Identifying host-selected traits is crucial to understanding the processes that govern the evolving interactions between animals and symbiotic microbes. Current experimental approaches mainly focus on the model bacteria, like hypermutating Escherichia coli or the evolutionary changes of wild stains by host transmissions. A method called atmospheric and room temperature plasma (ARTP) may overcome the bottleneck of low spontaneous mutation rates while maintaining mild conditions for the gut bacteria. RESULTS: We established an experimental symbiotic system with gnotobiotic bee models to unravel the molecular mechanisms promoting host colonization. By in vivo serial passage, we tracked the genetic changes of ARTP-treated Snodgrassella strains from Bombus terrestris in the non-native honeybee host. We observed that passaged isolates showing genetic changes in the mutual gliding locus have a competitive advantage in the non-native host. Specifically, alleles in the orphan mglB, the GTPase activating protein, promoted colonization potentially by altering the type IV pili-dependent motility of the cells. Finally, competition assays confirmed that the mutations out-competed the ancestral strain in the non-native honeybee gut but not in the native host. CONCLUSIONS: Using the ARTP mutagenesis to generate a mutation library of gut symbionts, we explored the potential genetic mechanisms for improved gut colonization in non-native hosts. Our findings demonstrate the implication of the cell mutual-gliding motility in host association and provide an experimental system for future study on host-microbe interactions. Video Abstract.

Effects of ambient air pollution on the hospitalization risk and economic burden of mental disorders in Qingdao, China.

OBJECTIVE: The aim of this study was to examine the impacts of short-term exposure to air pollutants on hospitalizations for mental disorders (MDs) in Qingdao, a Chinese coastal city, and to assess the corresponding hospitalization risk and economic cost. METHODS: Daily data on MD hospitalizations and environmental variables were collected from January 1, 2015, to December 31, 2019. An overdispersed generalized additive model was used to estimate the association between air pollution and MD hospitalizations. The cost of illness method was applied to calculate the corresponding economic burden. RESULTS: With each 10 µg/m3 increase in the concentration of fine particulate matter (PM2.5) at lag05, inhalable particulate matter (PM10) at lag0, sulfur dioxide (SO2) at lag06 and ozone (O3) at lag0, the corresponding relative risks (RRs) and 95% confidence intervals (CIs) were 1.0182 (1.0035-1.0332), 1.0063 (1.0001-1.0126), 1.0997 (1.0200-1.1885) and 1.0099 (1.0005-1.0194), respectively. However, no significant effects of nitrogen dioxide (NO2) or carbon monoxide (CO) were found. Stratified analysis showed that males were susceptible to SO2 and O3, while females were susceptible to PM2.5. Older individuals (≥ 45 years) were more vulnerable to air pollutants (PM2.5, PM10, SO2 and O3) than younger individuals (< 45 years). Taking the Global Air Quality Guidelines 2021 as a reference, 8.71% (2,168 cases) of MD hospitalizations were attributable to air pollutant exposure, with a total economic burden of 154.36 million RMB. CONCLUSION: Short-term exposure to air pollution was associated with an increased risk of hospitalization for MDs. The economic advantages of further reducing air pollution are enormous.

The fecal microbiota from children with autism impact gut metabolism and learning and memory abilities of honeybees.

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders, with an increasing incidence. Gastrointestinal symptoms are common comorbidities of ASD. The gut microbiota composition of children with autism is distinct from that of typical developmental (TD) children, suggesting that the gut microbiota probably influences on hosts via the microbiota-gut-brain axis. However, the relationship between intestinal dysbiosis and host brain function remains unclear. In this study, we creatively developed a honeybee model and investigated the potential effects of fecal microbiota on hosts. Fecal microbiota from children with autism and TD children were transplanted into microbiota-free honeybees (Apis mellifera), resulting in induced ASD-fecal microbiota transplantation (FMT) honeybees (A-BEE group) and TD-FMT honeybees (T-BEE group), respectively. We found that cognitive abilities of honeybees in the A-BEE group were significantly impaired in olfactory proboscis extension response conditioning. Metagenomics was used to evaluate fecal microbiota colonization, revealing several differential species responsible for altered tryptophan metabolism and taurine metabolism within the bee gut, including Bacteroides dorei, Bacteroides fragilis, Lactobacillus gasseri, and Lactobacillus paragasseri. Furthermore, fecal microbiota from children with autism downregulated brain genes involved in neural signaling and synaptic transmission within honeybees. Notably, differentially spliced genes observed within brains of honeybees from the A-BEE group largely overlapped with those identified in human diagnosed with autism via SFARI and SPARK gene sets. These differentially spliced genes were also enriched within pathways related to neural synaptic transmission. Our findings provide novel insights into the pivotal role of the human gut microbiota, which may contribute to neurological processes in honeybees. Additionally, we present a few research sources on gut-brain connections in ASD.

A Scoping Review of Tools and Techniques on Evaluating Population Health and Healthy Life Expectancy.

The concept of healthy life expectancy (HLE) integrates the ideas of life expectancy and health status, providing a valuable metric to evaluate both the length and quality of life. This paper seeks to aid policymakers in creating an inclusive HLE indicator system through a systematic review of methodologies for defining and measuring HLE, along with relevant published studies' descriptions. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews statement, two English language literature databases were researched from January 2020 to April 2023. Findings from empirical HLE-related studies were analyzed by extracting data on the study area, design, population, healthy state measurement tools, and results of studies using HLE indicators. The current analysis encompassed 48 empirical studies. Researchers discerned 11 unique HLE indicators within this corpus, each concentrating on a particular aspect. Furthermore, the analysis revealed 18 diverse instruments for evaluating health statuses, each varying in its definition of a healthy state, dimensions of measurement, and the categories of data employed. Therefore, merging global health concepts, HLE indicators, methodologies for assessing healthy states, and applied research demonstrations are essential for a consolidated HLE indicator system creation.

[Construction of a 10rolGLP-1-expressing glucose-lowing Saccharomyces cerevisiae by CRISPR/Cas9 technique].

To develop a novel glucose-lowering biomedicine with potential benefits in the treatment of type 2 diabetes, we used the 10rolGLP-1 gene previously constructed in our laboratory and the CRISPR/Cas9 genome editing technique to create an engineered Saccharomyces cerevisiae strain. The gRNA expression vector pYES2-gRNA, the donor vector pNK1-L-PGK-10rolGLP-1-R and the Cas9 expression vector pGADT7-Cas9 were constructed and co-transformed into S. cerevisiae INVSc1 strain, with the PGK-10rolGLP-1 expressing unit specifically knocked in through homologous recombination. Finally, an S. cerevisiae strain highly expressing the 10rolGLP-1 with glucose-lowering activity was obtained. SDS-PAGE and Western blotting results confirmed that two recombinant strains of S. cerevisiae stably expressed the 10rolGLP-1 and exhibited the desired glucose-lowering property when orally administered to mice. Hypoglycemic experiment results showed that the recombinant hypoglycemic S. cerevisiae strain offered a highly hypoglycemic effect on the diabetic mouse model, and the blood glucose decline was adagio, which can avoid the dangerous consequences caused by rapid decline in blood glucose. Moreover, the body weight and other symptoms such as polyuria also improved significantly, indicating that the orally hypoglycemic S. cerevisiae strain that we constructed may develop into an effective, safe, economic, practical and ideal functional food for type 2 diabetes mellitus treatment.

Preparation and antibacterial activity of coronarin E derivatives.

Coronarin E is a main diterpene ever isolated from Hedychium yunnanense. With the aim to enlarge its potential application, four butenolide derivatives (compounds 4a, 4b, 5a and 5b) were obtained from coronarin E via synthetic method, and their antibacterial effects were also evaluated. It is noteworthy that compounds 5a and 5b exhibited stronger antibacterial activities against most of the tested bacterial strains than ampicillin and kanamycin, two first- and second-line antimicrobials in clinical. For example, minimum inhibitory concentration (MIC) of 5a, 5b, ampicillin and kanamycin against Acinetobacter baumanii were 2, 1, 8 and 4 µg/mL, respectively, and MIC of the four compounds mentioned above against Klebsiella pneumonia were 1, 0.5, 16 and 4 µg/mL, respectively. The current studies not only enrich the structural diversity of diterpenes derived from Hedychium genus, but also provide potent candidates for the development of antibacterial medicines.

Seasonal associations between air pollutants and influenza in 10 cities of southern China.

Few studies have explored the associations between air pollutants and influenza across seasons, especially at large scales. This study aimed to evaluate seasons' modifying effects on associations between air pollutants and influenza from 10 cities of southern China. Through scientific evidence, it provides mitigation and adaptation strategies with practical guidelines to local health authorities and environmental protection agencies. Daily influenza incidence, meteorological, and air pollutants data from 2016 to 2019 were collected. Quasi-Poisson regression with a distributed lag nonlinear model was used to evaluate city-specific air pollutants and influenza associations. Meta-analysis was used to pool site-specific estimates. Attributable fractions (AFs) of influenza incidence due to pollutants were calculated. Stratified analyses were conducted by season, sex, and age. Overall, the cumulative relative risk (CRR) of influenza incidence for a 10-unit increase in PM2.5, PM10, SO2, NO2, and CO was 1.45 (95% CI: 1.25, 1.68), 1.53 (95% CI: 1.29, 1.81), 1.87 (95% CI: 1.40, 2.48), 1.74 (95% CI: 1.49, 2.03), and 1.19 (95% CI: 1.04, 1.36), respectively. Children aged 0-17 were more sensitive to air pollutants in spring and winter. PM10 had greater effect on influenza than PM2.5 in autumn, winter, and overall, lesser in spring. The overall AF due to PM2.5, PM10, SO2, NO2, and CO was 4.46% (95% eCI: 2.43%, 6.43%), 5.03% (95% eCI: 2.33%, 7.56%), 5.36% (95% eCI: 3.12%, 7.58%), 24.88% (95% eCI: 18.02%, 31.67%), and 23.22% (95% eCI: 17.56%, 28.61%), respectively. AF due to O3 was 10.00% (95% eCI: 4.76%, 14.95%) and 3.65% (95% eCI: 0.50%, 6.59%) in spring and summer, respectively. The seasonal variations in the associations between air pollutants and influenza in southern China would provide evidence to service providers for tailored intervention, especially for vulnerable populations.

Ti4+-dopamine/sodium alginate multicomponent complex derived N-doped TiO2@carbon nanocomposites for efficient removal of methylene blue.

A one-pot route for the preparation of TiO2@carbon nanocomposite from Ti4+/polysaccharide coordination complex has been developed and shown advantages in operation, cost, environment, etc. However, the photodegradation rate of methylene blue (MB) needs to be improved. N-doping has been proven as an efficient means to enhance photodegradation performance. Thus, the present study upgraded the TiO2@carbon nanocomposite to N-doped TiO2@carbon nanocomposite (N-TiO2@C) from Ti4+-dopamine/sodium alginate multicomponent complex. The composites were characterized by FT-IR, XRD, XPS, UV-vis DRS, TG-DTA, and SEM-EDS. The obtained TiO2 was a typical rutile phase, and the carboxyl groups existed on N-TiO2@C. The photocatalyst consequently showed high removal efficiency of MB. The cycling experiment additionally indicated the high stability of N-TiO2@C. The present work provided a novel route for preparing N-TiO2@C. Moreover, it can be extended to prepare N-doped polyvalent metal oxides@carbon composites from all water-soluble polysaccharides such as cellulose derivatives, starch, and guar gum.

Multi-Trait Genomic Prediction Improves Accuracy of Selection among Doubled Haploid Lines in Maize.

Recent advances in maize doubled haploid (DH) technology have enabled the development of large numbers of DH lines quickly and efficiently. However, testing all possible hybrid crosses among DH lines is a challenge. Phenotyping haploid progenitors created during the DH process could accelerate the selection of DH lines. Based on phenotypic and genotypic data of a DH population and its corresponding haploids, we compared phenotypes and estimated genetic correlations between the two populations, compared genomic prediction accuracy of multi-trait models against conventional univariate models within the DH population, and evaluated whether incorporating phenotypic data from haploid lines into a multi-trait model could better predict performance of DH lines. We found significant phenotypic differences between DH and haploid lines for nearly all traits; however, their genetic correlations between populations were moderate to strong. Furthermore, a multi-trait model taking into account genetic correlations between traits in the single-environment trial or genetic covariances in multi-environment trials can significantly increase genomic prediction accuracy. However, integrating information of haploid lines did not further improve our prediction. Our findings highlight the superiority of multi-trait models in predicting performance of DH lines in maize breeding, but do not support the routine phenotyping and selection on haploid progenitors of DH lines.

Transport of E. coli colloids and surrogate microspheres in the filtration process: Effects of flow rate, media size, and media species.

Drinking water safety risks caused by bacterial contamination from Escherichia coli (E. coli) have aroused widespread concern. Filtration is crucial to drinking water treatment and can effectively capture and remove E. coli colloids without producing toxic by-products. This work systematically simulated the operating conditions of filtration by determining the transport behavior of E. coli colloids in lab-scale columns. Microspheres were used as surrogates of bio-colloids and breakthrough curves were drawn and analyzed at different flow rates, media sizes, and media species. The impact of media species on colloidal retention might be underestimated in the filtration process, and the removal efficiency of E. coli colloids varied by more than 59% between different media. From the point of interface interaction, excellent removal efficiency may be due to the strong attractive force caused by more positive zeta potential on the media surface. The results indicated that there were differences in transport behavior and environmental sensitivity between the E. coli colloids and surrogates. The DLVO theory cannot analyze the transport behavior between different colloids in media with opposite charges, and it is not easy to quantify the contribution of media species accurately. The study focuses on the adjustable parameters of the filtration process and provides new insights for ensuring the safety of drinking water.

The Impact of Environmental Habitats and Diets on the Gut Microbiota Diversity of True Bugs (Hemiptera: Heteroptera).

Insects are generally associated with gut bacterial communities that benefit the hosts with respect to diet digestion, limiting resource supplementation, pathogen defense, and ecological niche expansion. Heteroptera (true bugs) represent one of the largest and most diverse insect lineages and comprise species consuming different diets and inhabiting various ecological niches, even including underwater. However, the bacterial symbiotic associations have been characterized for those basically restricted to herbivorous stink bugs of the infraorder Pentatomomorpha. The gut microbiota associated with the megadiverse heteropteran lineages and the implications of ecological and diet variance remain largely unknown. Here, we conducted a bacterial 16S rRNA amplicon sequencing of the gut microbiota across 30 species of true bugs representative of different ecological niches and diets. It was revealed that Proteobacteria and Firmicute were the predominant bacterial phyla. Environmental habitats and diets synergistically contributed to the diversity of the gut bacterial community of true bugs. True bugs living in aquatic environments harbored multiple bacterial taxa that were not present in their terrestrial counterparts. Carnivorous true bugs possessed distinct gut microbiota compared to phytophagous species. Particularly, assassin bugs of the family Reduviidae possessed a characterized gut microbiota predominantly composed of one Enterococcus with different Proteobacteria, implying a specific association between the gut bacteria and host. Overall, our findings highlight the importance of the comprehensive surveillance of gut microbiota association with true bugs for understanding the molecular mechanisms underpinning insect-bacteria symbiosis.

Temperature and influenza transmission: Risk assessment and attributable burden estimation among 30 cities in China.

BACKGROUND: Many studies have explored the epidemiological characteristics of influenza. However, most previous studies were conducted in a specific region without a national picture which is important to develop targeted strategies and measures on influenza control and prevention. OBJECTIVES: To explore the association between ambient temperature and incidence of influenza, to estimate the attributable risk from temperature in 30 Chinese cities with different climatic characteristics for a national picture, and to identify the vulnerable populations for national preventative policy development. METHODS: Daily meteorological and influenza incidence data from the 30 Chinese cities over the period 2016-19 were collected. We estimated the city-specific association between daily mean temperature and influenza incidence using a distributed lag non-linear model and evaluated the pooled effects using multivariate meta-analysis. The attributable fractions compared with reference temperature were calculated. Stratified analyses were performed by region, sex and age. RESULTS: Overall, an N-shape relationship between temperature and influenza incidence was found in China. The cumulative relative risk of the peak risk temperature (5.1 °C) was 2.13 (95%CI: 1.41, 3.22). And 60% (95%eCI: 54.3%, 64.3%) of influenza incidence was attributed to ambient temperature during the days with sensitive temperatures (1.6°C-14.4 °C). The ranges of sensitive temperatures and the attributable disease burden due to temperatures varied for different populations and regions. The residents in South China and the children aged ≤5 and 6-17 years had higher fractions attributable to sensitive temperatures. CONCLUSIONS: Tailored preventions targeting on most vulnerable populations and regions should be developed to reduce influenza burden from sensitive temperatures.

Strain-level profiling with picodroplet microfluidic cultivation reveals host-specific adaption of honeybee gut symbionts.

BACKGROUND: Symbiotic gut microbes have a rich genomic and metabolic pool and are closely related to hosts' health. Traditional sequencing profiling masks the genomic and phenotypic diversity among strains from the same species. Innovative droplet-based microfluidic cultivation may help to elucidate the inter-strain interactions. A limited number of bacterial phylotypes colonize the honeybee gut, while individual strains possess unique genomic potential and critical capabilities, which provides a particularly good model for strain-level analyses. RESULTS: Here, we construct a droplet-based microfluidic platform and generated ~ 6 × 108 droplets encapsulated with individual bacterial cells from the honeybee gut and cultivate in different media. Shotgun metagenomic analysis reveals significant changes in community structure after droplet-based cultivation, with certain species showing higher strain-level diversity than in gut samples. We obtain metagenome-assembled genomes, and comparative analysis reveal a potential novel cluster from Bifidobacterium in the honeybee. Interestingly, Lactobacillus panisapium strains obtained via droplet cultivation from Apis mellifera contain a unique set of genes encoding L-arabinofuranosidase, which is likely important for the survival of bacteria in competitive environments. CONCLUSIONS: By encapsulating single bacteria cells inside microfluidic droplets, we exclude potential interspecific competition for the enrichment of rare strains by shotgun sequencing at high resolution. The comparative genomic analysis reveals underlying mechanisms for host-specific adaptations, providing intriguing insights into microbe-microbe interactions. The current approach may facilitate the hunting for elusive bacteria and paves the way for large-scale studies of more complex animal microbial communities. Video Abstract.

TiO2/carbonaceous nanocomposite from titanium-alginate coordination compound.

TiO2-based materials have been developing rapidly as eco-friendly photocatalysts, but the inherent defects limited their application, such as rapid recombination of photogenerated electrons and wide bandgap. To obtain high-efficient TiO2/carbonaceous photocatalysts (TiO2/C), we prepared the nanocomposite by carbonizing titanium alginate coordination compound and studied their photocatalytic performance against methylene blue (MB) under simulated sunlight irradiation. The resultant nanocomposites were characterized by FT-IR, XPS, XRD, SEM-EDS, TG-DTG, UV-DRS, and N2 adsorption-desorption analysis. The carbon mainly existed in the outer layer of TiO2/C composites, contributing to the optical sensibilization. As a result, the degradation efficiency of sample TiO2/C-20 to MB could reach 97.47% within 15 min under simulated sunlight. The samples also possessed high stability, proved by the 0.72% reduction in photodegradation ratio after five cyclic tests. The present study proved the feasibility of preparing photocatalyst from titanium-alginate coordination compound and provided an extensible approach for preparing high-efficiency photocatalysts from a polysaccharide-based coordination compound.

Asian corn borer damage is affected by rind penetration strength of corn stalks in a spatiotemporally dependent manner.

Asian corn borer, Ostrinia furnacalis (Guenée), is an important insect pest of maize throughout most of Asia. The rind of a maize stalk is a key barrier against corn borer larvae boring into the plant. There is a need to better understand the relationship between stalk strength and O. furnacalis larval injury, particularly for elite maize genotypes. To determine whether stalk strength is involved in maize resistance to O. furnacalis larval injury, 39 maize lines were evaluated in 2012 and 2013. Rind penetration strength (RPS) was measured at tassel (VT) and milk (R3) stages as a possible stalk resistance trait for O. furnacalis. RPS of primary ear internode at VT and R3 accounted for 37 and 38% of the variance in O. furnacalis injury (measured as number of holes) for simulated (artificially infested) first and second generation O. furnacalis, respectively. Relationships between stalk RPS values and tunnel length were weak. Results suggest that harder stalks have enhanced resistance to stalk boring but not to pith feeding or tunneling of O. furnacalis larvae. The RPS measures could provide classical maize breeders an important tool for evaluating stalk strength and corn borer resistance in maize. The assessments should focus on the internodes primary ear or above/below primary ear during both VT stage for first generation and R3 stage for second generation O. furnacalis resistance.

Strain-level analysis reveals the vertical microbial transmission during the life cycle of bumblebee.

BACKGROUND: Microbial acquisition and development of the gut microbiota impact the establishment of a healthy host-microbes symbiosis. Compared with other animals, the eusocial bumblebees and honeybees possess a simple, recurring, and similar set of gut microbiota. However, all bee gut phylotypes have high strain-level diversity. Gut communities of different bee species are composed of host-specific groups of strains. The variable genomic regions among strains of the same species often confer critical functional differences, such as carbon source utilization, essential for the natural selection of specific strains. The annual bumblebee colony founded by solitary queens enables tracking the transmission routes of gut bacteria during development stages. RESULTS: Here, we first showed the changes in the microbiome of individual bumblebees across their holometabolous life cycle. Some core gut bacteria persist throughout different stages of development. Gut microbiota of newly emerged workers always resembles those of their queens, suggesting a vertical transmission of strains from queens to the newborn workers. We then follow the dynamic changes in the gut community by comparing strain-level metagenomic profiles of queen-worker pairs longitudinally collected across different stages of the nest development. Species composition of both queen and worker shifts with the colony's growth, and the queen-to-worker vertical inheritance of specific strains was identified. Finally, comparative metagenome analysis showed clear host-specificity for microbes across different bee hosts. Species from honeybees often possess a higher level of strain variation, and they also exhibited more complex gene repertoires linked to polysaccharide digestion. Our results demonstrate bacterial transmission events in bumblebee, highlighting the role of social interactions in driving the microbiota composition. CONCLUSIONS: By the community-wide metagenomic analysis based on the custom genomic database of bee gut bacteria, we reveal strain transmission events at high resolution and the dynamic changes in community structure along with the colony development. The social annual life cycle of bumblebees is key for the acquisition and development of the gut microbiota. Further studies using the bumblebee model will advance our understanding of the microbiome transmission and the underlying mechanisms, such as strain competition and niche selection. Video Abstract.

Long Non-coding RNAs in Pathogenesis of Neurodegenerative Diseases.

Emerging evidence addresses the link between the aberrant epigenetic regulation of gene expression and numerous diseases including neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). LncRNAs, a class of ncRNAs, have length of 200 nt or more, some of which crucially regulate a variety of biological processes such as epigenetic-mediated chromatin remodeling, mRNA stability, X-chromosome inactivation and imprinting. Aberrant regulation of the lncRNAs contributes to pathogenesis of many diseases, such as the neurological disorders at the transcriptional and post-transcriptional levels. In this review, we highlight the latest research progress on the contributions of some lncRNAs to the pathogenesis of neurodegenerative diseases via varied mechanisms, such as autophagy regulation, Aß deposition, neuroinflammation, Tau phosphorylation and α-synuclein aggregation. Meanwhile, we also address the potential challenges on the lncRNAs-mediated epigenetic study to further understand the molecular mechanism of the neurodegenerative diseases.

Comparison of ARIMA and LSTM in Forecasting the Incidence of HFMD Combined and Uncombined with Exogenous Meteorological Variables in Ningbo, China.

BACKGROUND: This study intends to identify the best model for predicting the incidence of hand, foot and mouth disease (HFMD) in Ningbo by comparing Autoregressive Integrated Moving Average (ARIMA) and Long Short-Term Memory Neural Network (LSTM) models combined and uncombined with exogenous meteorological variables. METHODS: The data of daily HFMD incidence in Ningbo from January 2014 to November 2017 were set as the training set, and the data of December 2017 were set as the test set. ARIMA and LSTM models combined and uncombined with exogenous meteorological variables were adopted to fit the daily incidence of HFMD by using the data of the training set. The forecasting performances of the four fitted models were verified by using the data of the test set. Root mean square error (RMSE) was selected as the main measure to evaluate the performance of the models. RESULTS: The RMSE for multivariate LSTM, univariate LSTM, ARIMA and ARIMAX (Autoregressive Integrated Moving Average Model with Exogenous Input Variables) was 10.78, 11.20, 12.43 and 14.73, respectively. The LSTM model with exogenous meteorological variables has the best performance among the four models and meteorological variables can increase the prediction accuracy of LSTM model. For the ARIMA model, exogenous meteorological variables did not increase the prediction accuracy but became the interference factor of the model. CONCLUSIONS: Multivariate LSTM is the best among the four models to fit the daily incidence of HFMD in Ningbo. It can provide a scientific method to build the HFMD early warning system and the methodology can also be applied to other communicable diseases.