The role of gut microbiota in mediating increased toxicity of nano-sized polystyrene compared to micro-sized polystyrene in mice.

Microplastics (MPs) are widespread environmental contaminants that have been detected in animals and humans. However, their toxic effects on terrestrial mammals and the underlying mechanisms are still not well understood. Herein, we explored the role of gut microbiota in mediating the toxicity of micro- and nano-sized polystyrene plastics (PS-MPs/PS-NPs) using an antibiotic depleted mice model. The results showed that PS-MPs and PS-NPs exposure disrupted the composition and structure of the gut microbiota. Specifically, these particles led to an increase in pathogenic Esherichia-shigella, while depleting probiotics such as Akkermansia and Lactobacillus. Comparatively, PS-NPs particles had more pronounced effect, leading to obviously shifted the colon transcriptional profiles characterized by inducing the enrichment of colon metabolism and immune-related pathways (i.e., upregulated in genes like udgh, ugt1a1, ugt1a6a, ugt1a7c and ugt2b34). Additionally, both PS-MPs and PS-NPs induced oxidative stress, gut-liver damage and systemic inflammation in mice. Mechanistically, we confirmed that PS particles disturbed gut microbiota, activating TLR2-My88-NF-κB pathway to trigger the release of inflammatory cytokine IL-1ß and TNF-α. The damage and inflammation caused by both size of PS particles was alleviated when the gut microbiota was depleted. In conclusion, our findings deepen the understanding of the molecule mechanisms by which gut microbiota mediate the toxicity of PS particles, informing health implications of MPs pollution.

Promoting effect of lanthanum doping on photovoltaic performance of CZTSSe solar cells.

A large open-circuit voltage (VOC) deficit is the major challenge hindering the efficiency improvement of Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. Cation substitution, or doping, is usually an effective strategy to achieve carrier regulation and improve efficiency. In this work, we developed a rare-earth element lanthanum (La) doped CZTSSe thin-film solar cell by directly introducing La3+ ions into the CZTS precursor solution. Such a proposed La doping approach could effectively enhance light harvesting, adjust the bandgap, and increase the electron diffusion length. Furthermore, appropriate concentrations of La doping can reduce harmful defect cluster. Benefiting from the La doping, the VOC significantly increases from 431 to 497 mV. Consequently, the power conversion efficiency is enhanced significantly from 6.54% (VOC = 431 mV, JSC = 25.50 mA/cm2, FF = 58.28%) for the reference cell to 10.21% (VOC = 497 mV, JSC = 35.20 mA/cm2, FF = 58.41%) for the optimized La-doped cell. This research provides a new direction for enhancing the performance of CZTSSe cells, offering promising prospects for the future of CZTSSe thin-film solar cells.

Landscape and risk assessment of microplastic contamination in farmed oysters and seawater along the coastline of China.

Microplastic (MP) pollution poses a significant threat to marine ecosystem and seafood safety. However, comprehensive and comparable assessments of MP profiles and their ecological and health in Chinese farming oysters are lacking. This study utilized laser infrared imaging spectrometer (LDIR) to quantify MPs in oysters and its farming seawater at 18 sites along Chinese coastlines. Results revealed a total of 3492 MPs in farmed oysters and seawater, representing 34 MP types, with 20-100 µm MP fragments being the dominant. Polyurethane (PU) emerged as the predominant MP type in oysters, while polysulfones were more commonly detected in seawater. Notably, oysters from the Bohai Sea exhibited a higher abundance of MPs (13.62 ± 2.02 items/g) and estimated daily microplastic intake (EDI, 2.14 ± 0.26 items/g/kg·bw/day), indicating a greater potential health risk in the area. Meanwhile, seawater from the Yellow Sea displayed a higher level (193.0 ± 110.7 items/L), indicating a greater ecological risk in this region. Given the pervasiveness and abundance of PU and its high correlation with other MP types, we proposed PU as a promising indicator for monitoring and assessing the risk MP pollution in mariculture in China. These findings provide valuable insights into the extent and characteristics of MP pollution in farmed oysters and seawater in China.

MoOx Synaptic Memristor with Programmable Multilevel Conductance for Reliable Neuromorphic Hardware.

Memristor holds great potential for enabling next-generation neuromorphic computing hardware. Controlling the interfacial characteristics of the device is critical for seamlessly integrating and replicating the synaptic dynamic behaviors; however, it is commonly overlooked. Herein, we report the straightforward oxidation of a Mo electrode in air to design MoOx memristors that exhibit nonvolatile ultrafast switching (0.6-0.8 mV/decade, <1 mV/decade) with a high on/off ratio (>104), a long durability (>104 s), a low power consumption (17.9 µW), excellent device-to-device uniformity, ingeniously synaptic behavior, and finely programmable multilevel analog switching. The analyzed physical mechanism of the observed resistive switching behavior might be the conductive filaments formed by the oxygen vacancies. Intriguingly, upon organization into memristor-based crossbar arrays, in addition to simulated multipattern memorization, edge detection on random images can be implemented well by parallel processing of pixels using a 3 × 3 × 2 array of Prewitt filter groups. These are vital functions for neural system hardware in efficient in-memory computing neural systems with massive parallelism beyond a von Neumann architecture.

Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening.

Hand, foot, and mouth disease (HFMD) is a common pediatric illness mainly caused by enteroviruses, which are important human pathogens. Currently, there are no available antiviral agents for the therapy of enterovirus infection. In this study, an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed. Using this screening system, we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors. Fangchinoline (FAN), a bis-benzylisoquinoline alkaloid, exhibits potential inhibitory effects against various enteroviruses that cause HFMD, such as EV-A71, CV-A10, CV-B3 and CV-A16. Further investigations revealed that FAN targets the early stage of the enterovirus life cycle. Through the selection of FAN-resistant EV-A71 viruses, we demonstrated that the VP1 protein could be a potential target of FAN, as two mutations in VP1 (E145G and V258I) resulted in viral resistance to FAN. Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

Analysis of extracellular and intracellular antibiotic resistance genes in commercial organic fertilizers reveals a non-negligible risk posed by extracellular genes.

Livestock manure is known to be a significant reservoir of antibiotic resistance genes (ARGs), posing a major threat to human health and animal safety. ARGs are found in both intracellular and extracellular DNA fractions. However, there has been no comprehensive analysis of these fractions in commercial organic fertilizers (COFs). The present study conducted a systematic survey of the profiles of intracellular ARGs (iARGs) and extracellular ARGs (eARGs) and their contributing factor in COFs in Northern China. Results showed that the ARG diversity in COFs (i.e., 57 iARGs and 53 eARGs) was significantly lower than that in cow dung (i.e., 68 iARGs and 69 eARGs). The total abundance of iARGs and eARGs decreased by 85.7% and 75.8%, respectively, after compost processing, and there were no significant differences between iARGs and eARGs in COFs (P > 0.05). Notably, the relative abundance of Campilobacterota decreased significantly (99.1-100.0%) after composting, while that of Actinobacteriota and Firmicutes increased by 21.1% and 29.7%, respectively, becoming the dominant bacteria in COFs. Co-occurrence analysis showed that microorganisms and mobile genetic elements (MGEs) were more closely related to eARGs than iARGs in COFs. And structural equation models (SEMs) further verified that microbial community was an essential factor regulating iARGs and eARGs variation in COFs, with a direct influence (λ = 0.74 and 0.62, P < 0.01), following by similar effects of MGEs (λ = 0.59 and 0.43, P < 0.05). These findings indicate the need to separate eARGs and iARGs when assessing the risk of dissemination and during removal management in the environment.

Occurrence and dissemination of antibiotic resistance genes in the Yellow River basin: focused on family farms.

As an emerging contaminant, antibiotic resistance genes (ARGs) have attracted growing attention, owing to their widespread dissemination and potential risk in the farming environment. However, ARG pollution from family livestock farms in the Yellow River basin, one of the main irrigation water sources in the North China Plain, remains unclear. Herein, we targeted 21 typical family farms to assess the occurrence patterns of ARGs in livestock waste and its influence on ARGs in receiving environment by real-time quantitative PCR (qPCR). Results showed that common ARGs were highly prevalent in family livestock waste, and tet-ARGs and sul-ARGs were the most abundant in these family farms. Most ARG levels in fresh feces of different animals varied, as the trend of chicken farms (broilers > laying hens) > swine farms (piglets > fattening pigs > boars and sows) > cattle farms (dairy cattle > beef cattle). The effect of natural composting on removing ARGs for chicken manure was better than that for cattle manure, while lagoon storage was not effective in removing ARGs from family livestock wastewater. More troublesomely, considerable amounts of ARGs were discharged with manure application, further leading to the ARG increase in farmland soil (up to 58-119 times), which would exert adverse impacts on human health and ecological safety.

Vermicompost: In situ retardant of antibiotic resistome accumulation in cropland soils.

The dissemination of antibiotic resistance genes (ARGs) in soil has become a global environmental issue. Vermicomposting is gaining prominence in agricultural practices as a soil amendment to improve soil quality. However, its impact on soil ARGs remains unclear when it occurs in farmland. We comprehensively explored the evolution and fate of ARGs and their hosts in the field soil profiles under vermicompost application for more than 3 years. Vermicompost application increased several ARG loads in soil environment but decreased the high-risk bla-ARGs (blaampC, blaNDM, and blaGES-1) by log(0.04 - 0.43). ARGs in soil amended with vermicompost primarily occurred in topsoil (approximately 1.04-fold of unfertilized soil), but it is worth noting that their levels in the 40-60 cm soil layer were the same or even less than in the unfertilized soil. The microbial community structure changed in soil profiles after vermicompost application. Vermicompost application altered the microbial community structure in soil profiles, showing that the dominant bacteria (i.e., Proteobacteria, Actinobacteriota, Firmicutes) were decreased 2.62%-5.48% with the increase of soil depth. A network analysis further revealed that most of ARG dominant host bacteria did not migrate from surface soil to deep soil. In particular, those host bacteria harboring high-risk bla-ARGs were primarily concentrated in the surface soil. This study highlights a lower risk of the propagation of ARGs caused by vermicompost application and provides a novel approach to reduce and relieve the dissemination of ARGs derived from animals in agricultural production.

Molecular characterization of human bocavirus in municipal wastewaters using amplicon target sequencing.

Human bocavirus (HBoV) is an emerging health concern worldwide, associated with range of clinical manifestations, including gastroenteritis and respiratory infections. Therefore, it is crucial to comprehend and minimize their prevalence in different systems. In this study, we conducted regular sampling throughout the year in two different sizes and work processes of wastewater treatment plants (WWTPs) in Tianjin, China. Our objective was to investigate the occurrence, prevalence, and endurance of HBoV in wastewater, while also evaluating the efficacy of amplicon target sequencing in directly detecting HBoV in wastewater. At two WWTPs, HBoV2 (45.51 %-45.67 %) and HBoV3 (38.30 %-40.25 %) were the most common genotypes identified, and the mean concentration range of HBoV was 2.54-7.40 log10 equivalent copies/l as determined by multiplex real-time quantitative PCR assay. A positive rate of HBoV was found in 96.6 % (29/30) samples of A-WWTP, and 96.6 % (26/27) samples of B-WWTP. The phylogenetic analysis indicated that the nucleotide similarity between the HBoV DNA sequences to the reference HBoV sequences published globally ranged from 90.14 %-100 %. A significant variation in the read abundance of HBoV2 and HBoV3 in two wastewater treatment plants (p < 0.05) was detected, specifically in the Winter and Summer seasons. The findings revealed a strong correlation between the genotypes detected in wastewater and the clinical data across various regions in China. In addition, it is worth mentioning that HBoV4 was exclusively detected in wastewater and not found in the clinical samples from patients. This study highlights the high prevalence of human bocavirus in municipal wastewater. This finding illustrates that amplicon target sequencing can amplify a wide variety of viruses, enabling the identification of newly discovered viruses.

Mobile genetic elements affect the dissemination of antibiotic resistance genes (ARGs) of clinical importance in the environment.

The prevalence of antibiotic resistance genes (ARGs) in the environment is a quintessential One Health issue that threats both human and ecosystem health; however, the source and transmission of ARGs, especially clinically important ARGs (CLIARGs), in the environment have not yet been well studied. In the present study, shotgun metagenomic approaches were used to characterize the microbiome, resistome, and mobilome composition in human feces and six different environment sample types in South China. Overall, the resistome harbored 157 CLIARGs, with specific ARG hotspots (e.g., human feces, wastewater treatment plants, livestock manure and wastewater) excreting significantly higher abundance of CLIARGs compared with the natural environment. A redundancy analysis (RDA) was performed and revealed that the bacterial community compositions and mobile genetic elements (MGEs) explained 55.08% and 34.68% of the variations in ARG abundance, respectively, indicating that both bacterial community and MGEs are key contributors to the maintenance and dissemination of CLIARGs in the environment. The network analysis revealed non-random co-occurrence patterns between 200 bacterial genera and 147 CLIARGs, as well as between 135 MGEs and 123 CLIARGs. In addition to numerous co-shared CLIARGs among different sample types, the source tracking program based on the FEAST probabilistic model was used to estimate the relative contributions of the CLIARGs from potential sources to the natural environment. The source tracking analysis results delineated that mobilome, more than microbiome, contributed CLIARG transmission from those ARG hotspots into natural environment, and the MGEs in WWTPs seem to play the most significant role in the spread of CLIARGs to the natural environment (average contribution 32.9%-46.4%). Overall, this study demonstrated the distribution and dissemination of CLIARGs in the environment, and aimed to better inform strategies to control the spread of CLIARGs into the natural environment.

Tracking the extracellular and intracellular antibiotic resistance genes across whole year in wastewater of intensive dairy farm.

Monitoring the annual variation of antibiotic resistance genes (ARGs) in livestock wastewater is important for determining the high-risk period of transfer and spread of animal-derived antibiotic resistance into the environment. However, the knowledge regarding the variation patterns of ARGs, especially intracellular ARGs (iARGs) and extracellular ARGs (eARGs), over time in livestock wastewater is still unclear. Herein, we conducted a year-round study to trace the profiles of ARGs at a Chinese-intensive dairy farm, focusing on the shifts observed in different months. The results showed significant differences in the composition and variation between iARGs and eARGs. Tetracycline, sulfonamide, and macrolide resistance genes were the major types of iARGs, while cfr was the major type of eARG. The environmental adaptations of the host bacteria determine whether ARGs appear as intracellular or extracellular forms. The total abundance of ARGs was higher from April to September, which can be attributed to the favorable climatic conditions for bacterial colonization and increased antibiotic administration during this period. Integron was found to be highly correlated with most iARGs, potentially playing a role in the presence of these genes within cells and their similar transmission patterns in wastewater. The intracellular and extracellular bacterial communities were significantly different, primarily because of variations in bacterial adaptability to the high salt and anaerobic environment. The intracellular co-occurrence network indicated that some dominant genera in wastewater, such as Turicibacter, Clostridium IV, Cloacibacillus, Subdivision5_genera_incertae_sedis, Saccharibacteria_genera_incertae_sedis and Halomonas, were potential hosts for many ARGs. To the best of our knowledge, this study demonstrates, for the first time, the annual variation of ARGs at critical points in the reuse of dairy farm wastewater. It also offers valuable insights into the prevention and control of ARGs derived from animals.

Screening and verification of antiviral compounds against HSV-1 using a method based on a plaque inhibition assay.

BACKGROUND: Herpes simplex virus type 1 (HSV-1) infection is a common viral disease that mainly causes oral lesions, but can also cause genital lesions in some instances. Current treatments with nucleoside analogs are limited by the emergence of drug resistance. Therefore, novel anti-HSV-1 drugs are urgently needed. METHODS: In this study, we screened a library of 2080 compounds for anti-HSV-1 activity using a plaque formation assay. We selected 11 potential inhibitors of HSV-1 and further evaluated their antiviral effects by plaque reduction assay and real-time polymerase chain reaction (qPCR). RESULTS: Five compounds, namely ginsenoside Rd, brassinolide, rosamultin, 3'-hydroxy puerarin, and clinafloxacin HCl, showed potent anti-HSV-1 activity and completely suppressed plaque formation at a concentration of 10 µM. Among them, clinafloxacin HCl, a fluoroquinolone antibiotic, exhibited a high selectivity index for HSV-1. CONCLUSIONS: Our findings suggest that these five compounds have potential antiviral properties against HSV-1 and may have different mechanisms of action. Further studies are warranted to elucidate the antiviral mechanisms of these compounds and to explore their therapeutic potential for HSV-1 infection.

Optoelectronic bio-synaptic plasticity on neotype kesterite memristor with switching ratio >104.

Optoelectronic memristors hold the most potential for realizing next-generation neuromorphic computation; however, memristive devices that can integrate excellent resistive switching and both electrical-/light-induced bio-synaptic behaviors are still challenging to develop. In this study, an artificial optoelectronic synapse is proposed and realized using a kesterite-based memristor with Cu2ZnSn(S,Se)4 (CZTSSe) as the switching material and Mo/Ag as the back/top electrode. Benefiting from unique electrical features and a bi-layered structure of CZTSSe, the memristor exhibits highly stable nonvolatile resistive switching with excellent spatial uniformity, concentrated Set/Reset voltage distribution (variation <0.08/0.02 V), high On/Off ratio (>104), and long retention time (>104 s). A possible mechanism of the switching behavior in such a device is proposed. Furthermore, these memristors successfully achieve essential bio-synaptic functions under both electrical and various visible light (470-655 nm) stimulations, including electrical-induced excitatory postsynaptic current, paired pulse facilitation, long-term potentiation, long-term depression, spike-timing-dependent plasticity, as well as light-stimulated short-/long-term plasticity and learning-forgetting-relearning process. As such, the proposed neotype kesterite-based memristor demonstrates significant potential in facilitating artificial optoelectronic synapses and enabling neuromorphic computation.

[Distribution characteristics and results of allergens in patients with allergic rhinitis in Ningxia area].

Objective:To investigate the distribution of allergens in patients with allergic rhinitis （AR） in Ningxia, and provide theoretical data for the prevention and treatment of AR in this region. Methods:A total of 1664 patients diagnosed with AR in the Otorhinolaryngology Head and Neck Surgery Department of Yinchuan First People's Hospital Outpatient Clinic from January 2018 to December 2021 were retrospectively collected. Use the allergen sIgE antibody detection kit （immunoblotting method） to detect inhalation and ingestion allergens in patients.Results: ①Among all AR patients, 1 158 cases were detected positive, resulting in the detection rate was 69.59%; ②The detection rate of inhalation allergen was 65.87%, and the detection rate of ingestion allergen was 19.83%; ③Mugwort was the most sensitive allergen, and 76.32% of the patients having a positive grade ≥3; ④Out of the patients, 294 cases （25.39%） were allergic to only one allergen, 244 cases （21.07%） were allergic to two allergens, and 620 cases （53.54%） were allergic to three or more allergens; ⑤During different seasons, the highest number of positive allergens detected was in the summer, with 968 cases （83.59%）. Mugwort was the main allergen during this season （69.01%）. After the COVID-19 epidemic, the total positive rate of sIgE tests in AR patients decreased compared to before, and the difference was statistically significant （P<0.001）; ⑥Mugwort, dog epithelium, mold combination, egg, peanut, soybean, Marine fish combination and fruit combination all showed statistically significant differences between different gender groups （P<0.05）; ⑦Common ragweed, mugwort, dust mite combination, cockroach, egg, milk, Marine fish combination, shrimp, fruit combination and nut combination all showed statistically significant differences among different age groups （P<0.05）; ⑧There were statistically significant differences in hay dust among different ethnic groups （P<0.05）. Conclusion:Artemisia argyi is the main allergen in Ningxia, and the distribution characteristics of different allergens are influenced by treatment season, the COVID-19 epidemic, gender, age, ethnicity, and other factors, showing certain distribution patterns and rules.

Selenite affected photosynthesis of Oryza sativa L. exposed to antimonite: Electron transfer, carbon fixation, pigment synthesis via a combined analysis of physiology and transcriptome.

Selenium (Se) is a microelement that can counteract (a)biotic stresses in plants. Excess antimony (Sb) will inhibit plant photosynthesis, which can be alleviated by appropriate doses of Se but the associated mechanisms at the molecular levels have not been fully explored. Here, a rice variety (Yongyou 9) was exposed to selenite [Se(IV), 0.2 and 0.8 mg L-1] alone or combined with antimonite [Sb(III), 5 and 10 mg L-1]. When compared to the 10 mg L-1 Sb treatment alone, addition of Se in a dose-dependent manner 1) reduced the heat dissipation efficiency resulting from the inhibited donors, Sb concentrations in shoots and roots, leaf concentrations of fructose, H2O2 and O2•-; 2) enhanced heat dissipation efficiency resulting from the inhibited accepters value, concentrations of Chl a, sucrose and starch, and the enzyme activity of adenosine diphosphate glucose pyrophosphorylase, sucrose phosphate synthase, and sucrose synthase; but 3) did not alter gas exchange parameters, concentrations of Chl b and total Chl, enzyme activity of soluble acid invertase, and values of maximum P700 signal, photochemical efficiency of PSI and electron transport rate of PSI. Se alleviated the damage caused by Sb to the oxygen-evolving complex and promoted the transfer of electrons from QA to QB. When compared to the 10 mg L-1 Sb treatment alone, addition of Se 1) up-regulated genes correlated to synthesis pathways of Chl, carotenoid, sucrose and glucose; 2) disturbed signal transduction pathway of abscisic acid; and 3) upregulated gene expression correlated to photosynthetic complexes (OsFd1, OsFER1 and OsFER2).

Implications of vermicompost on antibiotic resistance in tropical agricultural soils - A study in Hainan Island, China.

The contamination of antibiotic resistance genes (ARGs) associated with animal manure fertilization have attracted a global concern. Vermicompost has been widely popularized as an eco-friendly alternative to recycle animal manure on Hainan Island, China. However, the effects of vermicompost application on ARG spread and environmental fate in tropical agricultural soils remains undefined. Herein, the spatial prevalence and vertical behavior of ARGs in the soil profiles of vermicompost-applied agricultural regions were explored by a large-scale survey across Hainan Island. The results showed that although vermicompost application marginally enhanced the load of ARG pollution in the soil in Hainan, the ARGs derived from vermicompost did not eventually accumulate in the soil profile. The increase rate of ARGs in 40-60 cm soil layer was only 0.0015 % compared with that of unfertilized soil. Interestingly, vermicompost application reduced the abundance of high-risk ARGs, such as blaNDM and blaampC, by approximately one order of magnitude. Vermicompost was also observed to increase the abundance of beneficial bacteria, like Clostridium, and decrease those of Acidobacteriae, Planctomycetes and Verrucomicrobiae, which caused changes in the potential host bacteria of soil ARGs. Mobile genetic elements were further proven to be an essential factor that regulated the vertical dynamics of ARGs in vermicomposted soil, with a direct influence coefficient of 0.9975. This study demonstrated that the controllable risk associated with vermicompost application provided useful information to effectively reduce the threat of ARGs and promote the development of sustainable agriculture on Hainan Island.

Effects of soil habitat changes on antibiotic resistance genes and related microbiomes in paddy fields.

The changes of paddy soil habitat profoundly affect the structure and function of soil microorganisms, but how this process drives the growth and spread of manure- derived antibiotic resistance genes (ARGs) after entering the soil is unclear. Herein, this study explored the environmental fate and behavior of various ARGs in the paddy soil during rice growth period. Results showed that most ARG abundances in flooded soil was lower than that in non-flooded soil during rice growth (decreased by 33.4 %). And soil dry-wet alternation altered microbial community structure in paddy field (P < 0.05), showing that Actinobacteria and Firmicutes increased in proportion under non-flooded conditions, and Chloroflexi, Proteobacteria and Acidobacteria evolved into the dominant groups in flooded soil. Meanwhile, the correlation between ARGs and bacterial communities was stronger than that with mobile genetic elements (MGEs) in both flooded and non-flooded paddy soils. Furthermore, soil properties, especially oxidation reduction potential (ORP), were proved to be an essential factor in regulating the variability of ARGs in the whole rice growth stage by structural equation model, with a direct influence (λ = 0.38, P < 0.05), following by similar effects of bacterial communities and MGEs (λ = 0.36, P < 0.05; λ = 0.29, P < 0.05). This study demonstrated that soil dry-wet alternation effectively reduced the proliferation and dissemination of most ARGs in paddy fields, providing a novel agronomic measure for pollution control of antibiotic resistance in farmland ecosystem.

Exploring antibiotic resistance load in paddy-upland rotation fields amended with commercial organic and chemical/slow release fertilizer.

Agricultural fertilization caused the dissemination of antibiotic resistance genes (ARGs) in agro-ecological environment, which poses a global threat to crop-food safety and human health. However, few studies are known about the influence of different agricultural fertilization modes on antibiotic resistome in the paddy-upland rotation soils. Therefore, we conducted a field experiment to compare the effect of different fertilization (chemical fertilizer, slow release fertilizer and commercial organic fertilizer replacement at various rates) on soil antibiotic resistome in paddy-upland rotation fields. Results revealed that a total of 100 ARG subtypes and 9 mobile genetic elements (MGEs) occurred in paddy-upland rotation soil, among which MDR-ARGs, MLSB-ARGs and tet-ARGs were the dominant resistance determinants. Long-term agricultural fertilization remarkably facilitated the vertical accumulation of ARGs, in particular that bla ampC and tetO in relative abundance showed significant enrichment with increasing depth. It's worth noting that slow release fertilizer significantly increased soil ARGs, when comparable to manure with 20% replacing amount, but chemical fertilizer had only slight impact on soil ARGs. Fertilization modes affected soil microbial communities, mainly concentrated in the surface layer, while the proportion of Proteobacteria with the highest abundance decreased gradually with increasing depth. Furthermore, microbial community and MGEs were further proved to be essential factors in regulating the variability of ARGs of different fertilization modes by structural equation model, and had strong direct influence (λ = 0.61, p < 0.05; λ = 0. 55, p < 0.01). The results provided scientific guidance for reducing the spreading risk of ARGs and control ARG dissemination in agricultural fertilization.

Suppression of innate and acquired immunity in severe hand foot and mouth disease caused by EV71 infections in children.

Hand, foot, and mouth disease (HFMD) is a common children infectious disease caused by human enteroviruses. Most of the cases have minimal symptoms, however, some patients may develop serious neurological, cardiac complications, or even death. The pathological mechanism leading to severe HFMD is not clearly understood, and the immunological status of the individual patient may play an important role. Transcriptomes of peripheral blood mononuclear cells from EV71-infected patients (n = 45) and healthy controls (n = 36) were examined. Immune pathways were up-regulated in patients with mild disease symptoms (n = 11, M) compared to the healthy controls (n = 36, H), demonstrating an effective anti-viral response upon EV71 infection. However, in patients with severe symptoms (n = 23, S) as well as severe patients following treatment (n = 11, A), their innate and acquired immune pathways were down-regulated, indicating a global immunity suppression. Such immune suppression characteristics could thus provide an opportunity for early EV-71 infection prognosis prediction. Based on our cohort, an SVM model using RNA-seq expression levels of five genes (MCL1, ZBTB37, PLEKHM1P, IFNAR2 and YEATS2) was developed and achieved a high ROC-AUC (91·3%) in predicting severe HFMD. Meanwhile, qPCR fold-changes method was performed based three genes (MCL1, IFNAR2 and YEATS2) on additional cohort. This qPCR method achieved a ROC-AUC of 78.6% in predicting severe HFMD, which the patients could be distinguished in 2-3 h. Therefore, our models demonstrate the possibility of HFMD severity prediction based on the selected biomarkers that predict severe HFMD effectively.