Active and machine learning-enhanced discovery of new FGFR3 inhibitor, Rhapontin, through virtual screening of receptor structures and anti-cancer activity assessment.

Introduction: This study bridges traditional remedies and modern pharmacology by exploring the synergy between natural compounds and Ceritinib in treating Non-Small Cell Lung Cancer (NSCLC), aiming to enhance efficacy and reduce toxicities. Methods: Using a combined approach of computational analysis, machine learning, and experimental procedures, we identified and analyzed PD173074, Isoquercitrin, and Rhapontin as potential inhibitors of fibroblast growth factor receptor 3 (FGFR3). Machine learning algorithms guided the initial selection, followed by Quantitative Structure-Activity Relationship (QSAR) modeling and molecular dynamics simulations to evaluate the interaction dynamics and stability of Rhapontin. Physicochemical assessments further verified its drug-like properties and specificity. Results: Our experiments demonstrate that Rhapontin, when combined with Ceritinib, significantly suppresses tumor activity in NSCLC while sparing healthy cells. The molecular simulations and physicochemical evaluations confirm Rhapontin's stability and favorable interaction with FGFR3, highlighting its potential as an effective adjunct in NSCLC therapy. Discussion: The integration of natural compounds with established cancer therapies offers a promising avenue for enhancing treatment outcomes in NSCLC. By combining the ancient wisdom of natural remedies with the precision of modern science, this study contributes to evolving cancer treatment paradigms, potentially mitigating the side effects associated with current therapies.

Battery-free optoelectronic patch for photodynamic and light therapies in treating bacteria-infected wounds.

Light therapy is an effective approach for the treatment of a variety of challenging dermatological conditions. In contrast to existing methods involving high doses and large areas of illumination, alternative strategies based on wearable designs that utilize a low light dose over an extended period provide a precise and convenient treatment. In this study, we present a battery-free, skin-integrated optoelectronic patch that incorporates a coil-powered circuit, an array of microscale violet and red light emitting diodes (LEDs), and polymer microneedles (MNs) loaded with 5-aminolevulinic acid (5-ALA). These polymer MNs, based on the biodegradable composite materials of polyvinyl alcohol (PVA) and hyaluronic acid (HA), serve as light waveguides for optical access and a medium for drug release into deeper skin layers. Unlike conventional clinical photomedical appliances with a rigid and fixed light source, this flexible design allows for a conformable light source that can be applied directly to the skin. In animal models with bacterial-infected wounds, the experimental group with the combination treatment of metronomic photodynamic and light therapies reduced 2.48 log10 CFU mL-1 in bactericidal level compared to the control group, indicating an effective anti-infective response. Furthermore, post-treatment analysis revealed the activation of proregenerative genes in monocyte and macrophage cell populations, suggesting enhanced tissue regeneration, neovascularization, and dermal recovery. Overall, this optoelectronic patch design broadens the scope for targeting deep skin lesions, and provides an alternative with the functionality of standard clinical light therapy methods.

Co-application of concentrated biogas slurry and pyroligneous liquor mitigates ammonia emission and sustainably releases ammonium from paddy soil.

Biogas production causes vast amounts of biogas slurry (BS). Application of BS to croplands can substitute chemical fertilizers while result in higher ammonia emissions. Tremendous variation of ammonium concentration in different BSs induces imprecise substitution, while concentrated BS holds higher and more stable ammonium. Pyroligneous liquor, an acidic aqueous liquid from biochar production, can be used with concentrated BS to reduce ammonia emission. However, the effects of combining concentrated BS with pyroligneous liquor on ammonia emission and soil (nitrogen) N transformation have been poorly reported. In this study, a field experiment applying concentrated BS only, or combining with 5 %, 10 %, and 20 % pyroligneous liquor (v/v) for substituting 60 % N of single rice cultivation was conducted by contrast with chemical fertilization. The results showed that substituting chemical N fertilizers with concentrated BS increased 24.6 % ammonia emission. In comparison, applying 5 %, 10 %, and 20 % pyroligneous liquor with concentrated BS reduced 4.9 %, 20.3 %, and 24.4 % ammonia emissions, respectively. Applying concentrated BS with more pyroligneous liquor preserved higher ammonium and dissolved organic carbon in floodwater, and induced higher nitrate concentration after fertilization. Whereas soil ammonium and nitrate contents were decreased along with more pyroligneous liquor application before and after the topdressing and exhibited sustainable release until rice harvest. In comparison, the soil N mineralization and nitrification rates were occasionally elevated, while the activities of soil urease, protease, nitrate reductase, and nitrite reductase had multiple responses. Applying concentrated BS only, or combining with 5 %, 10, and 20 % pyroligneous liquor, have little effect on soil basic properties but inorganic N. In summary, applying concentrated BS with >10 % pyroligneous liquor could preserve more N with sustainable release and potentially lower N loss to the atmosphere, and we proposed that applying 13.5 % pyroligneous liquor in concentrated BS could achieve maximum soil fertility and minimum ammonia emission.

Molecular Epidemiology and Evolution of Coxsackievirus A14.

As the proportion of non-enterovirus 71 and non-coxsackievirus A16 which proportion of composition in the hand, foot, and mouth pathogenic spectrum gradually increases worldwide, the attention paid to other enteroviruses has increased. As a member of the species enterovirus A, coxsackievirus A14 (CVA14) has been epidemic around the world until now since it has been isolated. However, studies on CVA14 are poor and the effective population size, evolutionary dynamics, and recombination patterns of CVA14 are not well understood. In this study, 15 CVA14 strains were isolated from HFMD patients in mainland China from 2009 to 2019, and the complete sequences of CVA14 in GenBank as research objects were analyzed. CVA14 was divided into seven genotypes A-G based on an average nucleotide difference of the full-length VP1 coding region of more than 15%. Compared with the CVA14 prototype strain, the 15 CVA14 strains showed 84.0-84.7% nucleotide identity in the complete genome and 96.9-97.6% amino acid identity in the encoding region. Phylodynamic analysis based on 15 CVA14 strains and 22 full-length VP1 sequences in GenBank showed a mean substitution rate of 5.35 × 10-3 substitutions/site/year (95% HPD: 4.03-6.89 × 10-3) and the most recent common ancestor (tMRCA) of CVA14 dates back to 1942 (95% HPD: 1930-1950). The Bayesian skyline showed that the effective population size had experienced a decrease-increase-decrease fluctuation since 2004. The phylogeographic analysis indicated two and three possible migration paths in the world and mainland China, respectively. Four recombination patterns with others of species enterovirus A were observed in 15 CVA14 strains, among which coxsackievirus A2 (CVA2), coxsackievirus A4 (CVA4), coxsackievirus A6 (CVA6), coxsackievirus A8 (CVA8), and coxsackievirus A12 (CVA12) may act as recombinant donors in multiple regions. This study has filled the gap in the molecular epidemiological characteristics of CVA14, enriched the global CVA14 sequence database, and laid the epidemiological foundation for the future study of CVA14 worldwide.

Dissolved organic matter evolution and straw decomposition rate characterization under different water and fertilizer conditions based on three-dimensional fluorescence spectrum and deep learning.

Straw returning is a sustainable way to utilize agricultural solid waste resources. However, incomplete decomposition of straw will cause harm to crop growth and soil quality. Currently, there is a lack of technology to timely monitor the rate of straw decomposition. Dissolved organic matter (DOM) is the most active organic matter in soil and straw is mainly immersed in the soil in the form of DOM. In order to formulate reasonable straw returning management measures , a timely monitoring method of straw decomposition rate was developed in the study. Three water treatment (60%-65%, 70%-75% and 80%-85% maximum field capacity) and two fertilizer (organic fertilizer and chemical fertilizer) were set up in the management of straw returning to the field. Litterbag method was used to monitor the weight loss rate of straw decomposition under different water and fertilizer conditions in strawberry growth stage. The changes of DOM components were determined by three-dimensional fluorescence spectroscopy (3D-EEM). From the faster decomposition period to the slower decomposition period, the main components of DOM changed from protein-like components to humus-like components. At the end of the experiment, the relative content of humus-like components under the treatment of organic fertilizer and moderate water was the highest. Convolutional neural network (CNN) combined with 3D-EEM was used to identify the decomposition speed of straw. The classification precision of neural network validation set and test are 85.7% and 81.2%, respectively. In order to predict the decomposition rate of straw under different water and fertilizer conditions, 3D-EEM data of DOM were used as the input of CNN, parallel factor analysis (PARAFAC) and fluorescence region integral (FRI), and dissolved organic carbon data were used as the input of dissolved organic carbon linear prediction. The prediction model based on CNN had the best effect (R2 = 0.987). The results show that this method can effectively identify the spectral characteristics and predict the decomposition rate of straw under different conditions of water and fertilizer, which is helpful to promote the efficient decomposition of straw.

Circulation of Type 2 Vaccine-Derived Poliovirus in China in 2018-2019.

BACKGROUND: China implemented the globally synchronized switch from trivalent oral poliovirus vaccine (tOPV) to bivalent OPV (bOPV) on May 1, 2016. During April 2018 to May 2019, the first outbreak caused by type 2 circulating vaccine-derived poliovirus (cVDPV2) after the switch occurred in Xinjiang and Sichuan, China. Methods. We performed sequence analysis of VP1 and the whole genome to determine the genomic characteristics of type 2 cVDPVs, and carried out coverage surveys to assess the risk of viral propagation. Surveillance for environment and acute flaccid paralysis was intensified to enhance case ascertainment. Results. Comparison of the complete genomes between early (Xinjiang strain) and late strains (Sichuan strains) revealed that recombination pattern and reverse mutation of attenuation sites had been fixed early, but the mutations of the neutralizing antigenic sites were introduced over the circulation. The Markov Chain Monte Carlo tree showed that the cVDPV2 initial infection was April 2016, earlier than the switch. So, we speculated that the cVDPV2 was originated from tOPV recipients and spread among children with a low level of immunity against the type 2. CONCLUSIONS: The detection of this outbreak combined acute flaccid paralysis (AFP) surveillance with environmental surveillance (ES) indicates that ES should be expanded geographically to further complement AFP surveillance.

Fruit extracts from Phyllanthus emblica accentuate cadmium tolerance and accumulation in Platycladus orientalis: A new natural chelate for phytoextraction.

A key challenge for phytoextraction is the identification of high efficiency, growth-supporting, and low cost chelating agents. To date, no substance has satisfied all above criteria. This study investigated nine traditional Chinese herbs and found that Phyllanthus emblica fruit (FPE) extract could be utilised as an optimal chelate for the phytoextraction of cadmium (Cd)-contaminated soils. FPE application into soil at a ratio of 0.1% (w/w) significantly increased extractable Cd (by 43%) compared to the control. The success of FPE as a chelating agent was attributed to high quantities of polyphenol compounds (0.76%) and organic acids (9.6%), in particular, gallic acid (7.6%). Furthermore, antioxidative properties (1.4%) and free amino acids in FPE alleviated Cd-induced oxidant toxicity and enhanced plant biomass. FPE promoted 78% higher phytoextraction efficiency in Platycladus orientalis compared to traditional chelating agents (EDTA). Furthermore, 76% of FPE was degraded 90 days after the initial application, and there was no difference in extractable Cd between the treatment and control. FPE has been commercially produced at a lower market price than other biodegradable chelates. As a commercially available and cost-effective chelator, FPE could be utilised to treat Cd-contaminated soils without adverse environmental impacts.

Health risk assessment of heavy metal pollution in a soil-rice system: a case study in the Jin-Qu Basin of China.

A regional field survey of a total of 109 pairs of soil and rice samples was conducted to evaluate the health risks posed by heavy metals in the Jin-Qu Basin, China. The studied soils are characterized by acid (pH in mean level of 5.5), carbon rich (soil organic matter in mean of 33.6 g kg-1) and mainly contaminated by Cd (42.2% samples exceeded the standard value of 0.3 mg kg-1 (GB15618-2018)). The spatial distributions of Cd, Pb and Zn exhibited similar geographic trends. 34% and 30% of the rice samples containing Cd and Pb exceeded the threshold value of 0.2 mg kg-1 (GB2762-2017), respectively. The risk estimation of dietary intake had a target hazard quotient value of Cd of 0.918 and a hazard index value for rice consumption of 2.141. Totally, Cd and Pb were found to be the main components contributing to the potential health risks posed by non-carcinogenic effects for local inhabitants.

Cataloging of Cd Allocation in Late Rice Cultivars Grown in Polluted Gleysol: Implications for Selection of Cultivars with Minimal Risk to Human Health.

Cadmium (Cd) is a toxic trace metal that has polluted 20% of agricultural land in China where its concentration exceeds the standards for Chinese farmland. Plants are capable of accumulating Cd and other trace metals, but this capacity varies with species and cultivars within a species. Rice is a staple food consumed by half of the global population. In order to select safe late rice cultivars that are suitable late rice cultivars that can be cultivated in for growing in slightly contaminated soil, a two-year field experiment was conducted with 27 in the first year and 9 late rice cultivars in the second year. The results showed that plant Cd concentrations varied among the cultivars, with high magnitudes of variation occurred in straw and grains. Five genotypes including LR-12, LR-17, LR-24, LR-25 and LR-26 were identified as low accumulators for the first year while LR-15 and LR-17 were identified as promising cultivars based on Cd concentration in the polished rice grains (<0.02 mg kg-1 DW). In addition, these cultivars had favorable traits, including mineral nutrition and grain yield. Therefore, these genotypes should be considered for cultivation in slightly or moderately Cd contaminated soils.

Utilization of gibberellin fermentation residues with swine manure by two-step composting mediated by housefly maggot bioconversion.

The ecological disposal of gibberellin fermentation residues (GFRs) is urgently needed. This study explored a new method of direct GFR utilization with swine manure at different substitution proportions (0%, 20%, 40%, and 60%) using two-step composting mediated by housefly maggot bioconversion. Regarding maggot bioconversion, substitution of GFRs accelerated the temperature increase and water content decrease, slowed the pH increase, and enhanced the maggot conversion rate. Among the proportions, 20% GFR substitution had the highest maggot conversion rate of 15.15%. During the composting stage, GFR substitution promoted the initial temperature increase and the water content decrease and maintained a relatively low pH. However, only 20% substitution promoted the maturity of compost. The degradation rates of the gibberellin residue were all higher than 97% in the treatments with GFRs after two-step composting. High-throughput sequencing analysis showed that GFR substitution had significant effects on the microbial community structure during the whole process. However, the change in the microbial community was similar to that of conventional composting. Therefore, this innovative approach is feasible for GFR resource utilization, and substitution below 20% for swine manure is recommended.

Assessment of sunflower germplasm for phytoremediation of lead-polluted soil and production of seed oil and seed meal for human and animal consumption.

Phytoremediation is a valuable technology for mitigating soil contamination in agricultural lands, but phytoremediation without economic revenue is unfeasible for land owners and farmers. The use of crops with high biomass and bioenergy for phytoremediation is a unique strategy to derive supplementary benefits along with remediation activities. Sunflower (Helianthus annuus L.) is a high-biomass crop that can be used for the phytoremediation of polluted lands with additional advantages (biomass and oil). In this study, 40 germplasms of sunflower were screened in field conditions for phytoremediation with the possibility for oil and meal production. The study was carried out to the physiological maturity stage. All studied germplasms mopped up substantial concentrations of Pb, with maximum amounts in shoot > root > seed respectively. The phytoextraction efficiency of the germplasm was assessed in terms of the Transfer factor (TF), Metal removal efficiency (MRE) and Metal extraction ratio (MER). Among all assessed criteria, GP.8585 was found to be most appropriate for restoring moderately Pb-contaminated soil accompanied with providing high biomass and high yield production. The Pb content in the oil of GP.8585 was below the Food safety standard of China, with 59.5% oleic acid and 32.1% linoleic acid. Moreover, amino acid analysis in meal illustrated significant differences among essential and non-essential amino acids. Glutamic acid was found in the highest percentage (22.4%), whereas cysteine in the lowest percentage (1.3%). Therefore, its efficient phytoextraction ability and good quality edible oil and meal production makes GP.8585 the most convenient sunflower germplasm for phytoremediation of moderately Pb-contaminated soil, with fringe benefits to farmers and landowners.

Accumulation and distribution of cadmium and lead in 28 oilseed rape cultivars grown in a contaminated field.

Heavy metal pollution in soils has become an important concern for human health. Therefore, it is vital to develop suitable remediation strategies for contaminated soils. Oilseed rape tolerates high concentrations of heavy metals and is a promising candidate for the phytoextraction of cadmium (Cd) and lead (Pb) from metal-contaminated soils. A field experiment was conducted to evaluate 28 oilseed rape cultivars including Brassica napus L. and Brassica juncea L. for their ability to accumulate Cd and Pb. These cultivars were grown in a field co-contaminated with Cd (0.78 mg kg-1) and Pb (330 mg kg-1). The results showed that concentrations in shoots ranged from 1.22 to 3.01 mg kg-1 for Cd and from 10.8 to 29.5 mg kg-1 for Pb. Cadmium and Pb accumulations in shoots could reach 83.4 and 799 µg plant-1, respectively. The majority of translocation factors (TFs) for Cd (> 1.0) were higher than for Pb (≤ 1.0). However, concentrations of Cd and Pb in seeds were much lower, in the range of 0.04 to 0.21 mg kg-1 and 0.04 to 0.51 mg kg-1, respectively. The seed yields of oilseed rape varied from 1238 to 2904 kg ha-1, with a mean value of 2289 kg ha-1. Among the cultivars, three (OS-9, OS-12, and OS-15) were selected as Cd and Pb potential accumulators, with Cd accumulation in shoots being 2.74-3.70 times higher and Pb accumulation in shoots being 3.37-5.23 times higher as compared with the lowest accumulating cultivar. These selected cultivars (B. napus) have application potential for phytoextraction of Cd and Pb from polluted soils without stopping agricultural activities and accompanying food safety issues.

Identification of high cadmium-accumulating oilseed sunflower (Helianthus annuus) cultivars for phytoremediation of an Oxisol and an Inceptisol.

Forty oilseed sunflower cultivars were screened in two soil types for phytoremediation of Cd coupled with maximum biomass yield and oil production. Several cultivars exhibited a significant difference in biomass and yield with enhanced uptake in shoots and low accumulation in roots from two Cd-contaminated soil types, an Oxisol and an Iceptisol. The Transfer Factor of Cd was >1 in several cultivars in both soil types, where as a significant difference in phytoextraction of Cd was observed in the Oxisol (acidic soil), greater than in the Inceptisol (alkaline soil). The results revealed that of the 40 cultivars, S9178, Huanong 667in the Oxisol and cvs. DW 667, HN 667, Huanong 667 and 668F1 in the Inceptisol showed a high biomass, better yield and enhanced accumulation of Cd in the shoots but a lesser accumulation in oil. The screened cultivar S 9178 produced the greatest amount of oil (55.6%) with 77% oleic acid, which makes it suitable for human consumption. Cultivar Huanong 667 was found to be the highest accumulating cultivar in both soil types. It is therefore suggested that some sunflower cultivars do exhibit phytoremediation potential together with agro-production potential.

Emerging recombination of the C2 sub-genotype of HFMD-associated CV-A4 is persistently and extensively circulating in China.

Sporadic outbreaks caused by coxsackievirus A4 (CV-A4) have been reported worldwide. To further elucidate the detailed genetic characteristics and evolutionary recombination events of CV-A4, virus samples from nationwide hand, foot and mouth disease (HFMD) surveillance, encompassing 27 out of the 31 provinces in China, were investigated. Comprehensive and systematic phylogenetic analyses were performed by using 29 complete genomes, 142 complete CV-A4 VP1 sequences. Four genotypes (A, B, C and D) and five sub-genotypes (C1-C5) were re-identified based on the complete VP1 sequences. C2 is the predominant sub-genotype of CV-A4 associated with HFMD and has evolved into 3 clusters. Cluster 1 is a major cluster that has been persistently and extensively circulating in China since 2006 and has been associated with all severe cases. All the sequences showed high homology with the CV-A4 prototype in the P1 region, while higher identities with CV-A5, CV-14 and CV-16 in the P2 and P3 regions. Recombination analysis revealed that C2 had two specific genetic recombination patterns with other EV-A prototypes in the 5'-UTR and 3D region compared with C5. These recombination patterns might be associated with the increased transmissibility of C2 viruses, which were obtained due to their persistent and extensive circulation in populations.

The surveillance of the epidemiological and serotype characteristics of hand, foot, mouth disease in Neijiang city, China, 2010-2017: A retrospective study.

Hand, foot, and mouth disease (HFMD) is well recognized as one of the major threats to children's health globally. The increasing complexity of the etiology of HFMD still challenges disease control in China. There is little surveillance of the molecular epidemiological characteristics of the enteroviruses (EVs) that cause HFMD in Neijiang city or the Sichuan Basin area in Southwest China. In this study, demographic and epidemiological information for 14,928 probable HFMD cases was extracted and analyzed to describe the epidemic features of HFMD in Neijiang city from Jan 2010 to Dec 2017. The swab samples of select probable HFMD cases from 2012 to 2017 were tested by reverse transcription (RT) real-time PCR to identify the serotype distribution of EVs, and 110 randomly selected RT-real-time PCR positive samples were then amplified and analyzed for the VP1 or VP4 regions of EVs to further analyze the phylogenetic characteristics of the circulating strains in this area. The eight-year average annual incidence was 49.82 per 100,000 in Neijiang. The incidence rates varied between 19.51 and 70.73 per 100,000, demonstrating peaks of incidence in even-number years (2012, 2014 and 2016). The median age of the probable cases was 27 months and the interquartile range (25th to 75th percentile) of ages for the probable HFMD cases was between 14 and 42 months. The male-to-female ratio of the probable HFMD cases was 1.47:1, and scattered children were the major population classification (81.7%). Two epidemic peaks were observed: one major peak between April and July and the other lesser peak between October and December. Of 6513 probable cases tested with RT-real-time PCR, 4015 (61.6%) were positive for enterovirus with the serotype distribution as follows: EV71+, 30.1% (n = 1210); CV-A16+, 28.7% (n = 1154) and a sole pan-enterovirus+, 41.1% (n = 1651). A total of 91 cases (82.7%, 91/110) were successfully amplified and underwent phylogenetic analysis: all EV71+ cases were C4a serotype (n = 23/30); all CV-A16+ cases were B2b serotype (n = 24/30); of 42 sole pan-enterovirus+ samples, 20 were CV-A6, 14 were CV-A10 and the rest within this group were CV-A4 (n = 4), CV-A8 (n = 2), CV-A9 (n = 1) and CV-B3 (n = 1). Our findings provide important evidence that aids the improvement of strategies for vaccination against HFMD and comprehensive disease control in China.

Distribution, availability and translocation of heavy metals in soil-oilseed rape (Brassica napus L.) system related to soil properties.

Heavy metals contamination in agricultural soil has become a worldwide problem, and soil characteristics modulate metal availability in soils. Four field experiments were conducted simultaneously to evaluate concentration and distribution of cadmium (Cd) and lead (Pb) in 39 oilseed rape cultivars at four agricultural locations with different contamination levels of Cd and Pb, as well as the influence of soil characteristics together with soil total and bioavailable Cd and Pb concentration on metal transfer from soil to oilseed rape. Shoot concentrations of Cd and Pb in oilseed rape cultivars ranged from 0.09 to 3.18 and from 0.01 to 10.5 mg kg-1 across four sites. For most cultivars, Cd concentration in root or shoot were higher than pod and lowest in seed, while the highest Pb concentration was observed in root followed by shoot and seed. Stepwise multiple linear regression analysis allows for a better estimation of Cd and Pb concentration in oilseed rape while taking soil properties into consideration. The results demonstrated that Cd and Pb concentration in oilseed rape were correlated with soil organic matter (OM), cation exchange capacity (CEC), available phosphorus (AP), available potassium (AK), sand, soil total and available Cd and Pb concentration, and R2 varied from 0.993 to 0.999 (P < 0.05). The Cd and Pb levels found in oilseed rape indicated its phytoextraction potential for Cd and Pb co-contaminated agricultural soils in winter without stopping agricultural activities.

The emerging sub-genotype C2 of CoxsackievirusA10 Associated with Hand, Foot and Mouth Disease extensively circulating in mainland of China.

Coxsackievirus A10 (CV-A10) associated with Hand, foot, and mouth disease (HFMD) cases emerged increasingly in recent years. In this study, the samples from nation-wide HFMD surveillance, including 27 out of 31 provinces in China were investigated, and the continuous and extensive virological surveillance, covered 13 years, were conducted to provide a comprehensive molecular characterization analysis of CV-A10. 855 CV-A10 viruses (33 severe cases included), were isolated from HFMD children patients during 2009 to 2016 in China. 164 representative sequences from these viruses, together with 117 CV-A10 sequences downloaded from GenBank based on entire VP1 were recruited in this study. Two new genotypes (F and G) and two sub-genotypes (C1 and C2) were identified. Among 264 Chinese sequences, 9 of them were genotype B, 8 of them were C1, and the other (247) were C2, the predominant sub-genotype in China since 2012. Chinese C2 viruses showed obvious temporal characteristics and can be divided into 3 clusters (cluster 1~3). Cluster 3 viruses was circulating extensively during 2014 and 2016 with more severe cases. It is very necessary and important to continuously conduct the extensive virological surveillance for CV-A10, and further evolutionary studies will provide more evidence on its evolution and virulence.

Human infection with a novel, highly pathogenic avian influenza A (H5N6) virus: Virological and clinical findings.

BACKGROUND AND OBJECTIVES: Severe infection with avian influenza A (H5N6) virus in humans was identified first in 2014 in China. Before that, it was unknown or unclear if the disease or the pathogen affected people. This study illustrates the virological and clinical findings of a fatal H5N6 virus infection in a human patient. METHODS: We obtained and analyzed the clinical, epidemiological, and virological data from the patient. Reverse transcription polymerase chain reaction (RT-PCR), viral culture, and sequencing were conducted for determination of the causative pathogen. RESULTS: The patient, who presented with fever, severe pneumonia, leucopenia, and lymphopenia, developed septic shock and acute respiratory distress syndrome (ARDS), and died on day 10 after illness onset. A novel reassortant avian-origin influenza A (H5N6) virus was isolated from the throat swab or trachea aspirate of the patient. The virus was reassorted with the HA gene of clade 2.3.4.4 H5, the internal genes of clade 2.3.2.1 H5, and the NA gene of the H6N6 avian virus. The cleavage site of the HA gene contained multiple basic amino acids, indicating that the novel H5N6 virus was highly pathogenic in chicken. CONCLUSIONS: A novel, highly pathogenic avian influenza H5N6 virus with a backbone of H5N1 virus acquired from the NA gene from the H6N6 virus has been identified. It caused human infection resulting in severe respiratory disease.

An outbreak of type π vaccine-derived poliovirus in Sichuan province, China: emergence and circulation in an under-immunized population.

BACKGROUND: During August 2011-February 2012, an outbreak of type Π circulating vaccine-derived poliovirus (cVDPVs) occurred in Sichuan Province, China. METHODS: A field investigation of the outbreak was conducted to characterize outbreak isolates and to guide emergency response. Sequence analysis of poliovirus capsid protein VP1 was performed to determine the viral propagation, and a coverage survey was carried out for risk assessment. RESULTS: One clinical compatible polio case and three VDPV cases were determined in Ngawa County, Ngawa Tibetan and Qiang Autonomous Prefecture, Sichuan Province. Case patients were unimmunized children, 0.8-1 years old. Genetic sequencing showed that the isolates diverged from the VP1 region of the type Π Sabin strain by 5-12 nucleotides (nt) and shared the same 5 nt VP1 substitutions, which indicate single lineage of cVDPVs. Of the 7 acute flaccid paralysis cases (all>6 months) reported in Ngawa Prefecture in 2011, 4 (57.1%) cases (including 2 polio cases) did not receive oral attenuated poliovirus vaccine. Supplementary immunization activities (SIAs) were conducted in February-May, 2012, and the strain has not been isolated since. CONCLUSION: High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Risk assessments should be conducted regularly to pinpoint high risk areas or subpopulations, with SIAs developed if necessary.