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SARS-CoV-2 Omicron variant has presented significant challenges to current antibodies and vaccines. Herein, we systematically compared the efficacy of 50 human monoclonal antibodies (mAbs), covering the seven identified epitope classes of the SARS-CoV-2 RBD, against Omicron sub-variants BA.1, BA.1.1, BA.2, and BA.3. Binding and pseudovirus-based neutralizing assays revealed that 37 of the 50 mAbs lost neutralizing activities, whereas the others displayed variably decreased activities against the four Omicron sub-variants. BA.2 was found to be more sensitive to RBD-5 antibodies than the other sub-variants. Furthermore, a quaternary complex structure of BA.1 RBD with three mAbs showing different neutralizing potencies against Omicron provided a basis for understanding the immune evasion of Omicron sub-variants and revealed the lack of G446S mutation accounting for the sensitivity of BA.2 to RBD-5 mAbs. Our results may guide the application of the available mAbs and facilitate the development of universal therapeutic antibodies and vaccines against COVID-19.
Subject(s)
Antibodies, Neutralizing , COVID-19 , Antibodies, Monoclonal , Antibodies, Viral , COVID-19 Vaccines , Humans , Membrane Glycoproteins , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Viral Envelope ProteinsABSTRACT
Uncertainty remains on the threshold of ventilation rate in airborne transmission of SARS-CoV-2. We analyzed a COVID-19 outbreak in January 2020 in Hunan Province, China, involving an infected 24-year-old man, Mr. X, taking two subsequent buses, B1 and B2, in the same afternoon. We investigated the possibility of airborne transmission and the ventilation conditions for its occurrence. The ventilation rates on the buses were measured using a tracer-concentration decay method with the original driver on the original route. We measured and calculated the spread of the exhaled virus-laden droplet tracer from the suspected index case. Ten additional passengers were found to be infected, with seven of them (including one asymptomatic) on B1 and two on B2 when Mr. X was present, and one passenger infected on the subsequent B1 trip. B1 and B2 had time-averaged ventilation rates of approximately 1.7 and 3.2 L/s per person, respectively. The difference in ventilation rates and exposure time could explain why B1 had a higher attack rate than B2. Airborne transmission due to poor ventilation below 3.2 L/s played a role in this two-bus outbreak of COVID-19.
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RESEARCH QUESTION: What are the risks associated with cryopreserved semen collected during and after the coronavirus disease 2019 (COVID-19) pandemic wave in Wuhan, China? DESIGN: Retrospective cohort study involving young adult men who were qualified sperm donors at the Hunan Province Human Sperm Bank (China) during the pandemic wave (1 January 2020 to 30 January 2020) and after the wave and return to work (7 April 2020 to 30 May 30 2020). One hundred paired semen and blood specimens from 100 donors were included. One-step single-tube nested quantitative real-time polymerase chain reaction (OSN-qRT-PCR) was used to detect SARS-CoV-2. Moreover, to control the unacceptable risk of false-negative results, a second round of screening was performed with pooled RNA from negative semen samples using crystal digital PCR (cd-PCR). RESULTS: For individual blood and semen samples, the target genes, namely the nucleocapsid protein (N) and open reading frame (ORF-1ab) genes, tested negative in all of the 100 paired samples. Further, as per cd-PCR results, there were >20,000 droplets per well in the RNA for each combined sample and no positive droplets were present for either of the aforementioned target genes. A total of 100 paired semen and blood samples from these two groups tested negative for SARS-CoV-2. CONCLUSIONS: Cryopreserved semen at the Hunan Province Human Sperm Bank during and after the COVID-19 pandemic wave was free of SARS-CoV-2 and was judged safe for external use in the future.
Subject(s)
COVID-19 , Pandemics , China/epidemiology , Humans , Male , Real-Time Polymerase Chain Reaction , Retrospective Studies , SARS-CoV-2 , Semen , Sperm Banks , Spermatozoa , Young AdultABSTRACT
Urbanization and rural-urban migration are two factors driving global patterns of disease and mortality. There is significant concern about their potential impact on disease burden and the effectiveness of current control approaches. Few attempts have been made to increase our understanding of the relationship between urbanization and disease dynamics, although it is generally believed that urban living has contributed to reductions in communicable disease burden in industrialized countries. To investigate this relationship, we carried out spatiotemporal analyses using a 48-year-long dataset of hemorrhagic fever with renal syndrome incidence (HFRS; mainly caused by two serotypes of hantavirus in China: Hantaan virus and Seoul virus) and population movements in an important endemic area of south China during the period 1963-2010. Our findings indicate that epidemics coincide with urbanization, geographic expansion, and migrant movement over time. We found a biphasic inverted U-shaped relationship between HFRS incidence and urbanization, with various endemic turning points associated with economic growth rates in cities. Our results revealed the interrelatedness of urbanization, migration, and hantavirus epidemiology, potentially explaining why urbanizing cities with high economic growth exhibit extended epidemics. Our results also highlight contrasting effects of urbanization on zoonotic disease outbreaks during periods of economic development in China.
Subject(s)
Databases, Factual , Hantavirus Infections/epidemiology , Human Migration , Orthohantavirus , Urban Renewal , Zoonoses/epidemiology , Animals , China , Female , Humans , Incidence , Male , Zoonoses/virologyABSTRACT
OBJECTIVES: To investigate the epidemic situation of hand-foot-mouth disease (HFMD) in Hunan Province, China, from 2008 to 2019, as well as its spatial autocorrelation characteristics and spatial-temporal clustering, and to provide a reference for the prevention and control of HFMD in Hunan Province. METHODS: Spatial autocorrelation and spatial-temporal clustering analyses were used to analyze the monitoring data of HFMD in Hunan Province from 2008 to 2019. RESULTS: The epidemic situation of HFMD in Hunan Province from 2008 to 2019 showed obvious seasonal distribution, with a low incidence rate in January to March and a high incidence rate in April to July. As for population distribution, children aged 0-5 years had the highest number of HFMD cases and accounted for 95.89% (1 460 391/1 522 910) of all cases, with a mean annual incidence rate of 2 197.784/100 000, and scattered children had the highest number of cases and accounted for 82.59% (1 257 739/1 522 910) of all cases. The global spatial autocorrelation analysis showed that the onset of HFMD in Hunan Province showed a significant clustering distribution, and the local spatial autocorrelation analysis showed that the high clustering areas of HFMD were mainly the districts and counties of Changsha, Zhuzhou, and Yueyang cities. Time-space scanning showed that clustering time was mainly April to July; the cases were clustered in the northeast of Hunan Province from 2008 to 2010 and in the central part of Hunan Province from 2011 to 2019. CONCLUSIONS: The high incidence rate of HFMD is observed in April to July in Hunan Province. Children under 5 years of age are at a high risk of this disease. Spatial-temporal clustering is observed for the epidemic of HFMD, mainly clustered in the northeastern and central areas of Hunan Province. It is suggested that the results may be used as guidance to determine the key areas for HFMD prevention and control in Hunan Province and optimize the allocation of health resources.
Subject(s)
Hand, Foot and Mouth Disease , Child , Child, Preschool , China/epidemiology , Cluster Analysis , Hand, Foot and Mouth Disease/epidemiology , Humans , Incidence , Infant , Spatio-Temporal AnalysisABSTRACT
Melanogenesis, migration and proliferation of melanocytes are important factors that determine the hair colours of mammals. MicroRNAs (miRNAs) have been shown to be closely related to these processes. In melanocytes of alpacas, insulin-like growth factor 1 (IGF1) has been shown to improve melanogenesis through the cyclic AMP (cAMP) pathway. miR-379 was predicted to target insulin-like growth factor (IGF) receptor 1 (IGF1R), which binds to IGF1. Therefore, we hypothesized that miR-379 could mediate melanogenesis, migration and proliferation of melanocytes. Here, we report that miR-379 was highly expressed in alpaca melanocytes. Subsequent overexpression of miR-379 in alpaca melanocytes led to the generation of the phenotype of melanogenesis, proliferation and migration. In addition, the expression of genes related to these phenotypes in melanocytes was detected. Our results showed that miR-379 targets IGF1R in melanocytes. The overexpression of miR-379 stimulated dendrite extension or elongation and limited the perinuclear distribution of melanin, but inhibited melanogenesis via cAMP response element (CRE)-binding protein (CREB)/microphthalmia-associated transcription factor (MITF) pathway. miR-379 attenuated melanocyte migration by downregulating the focal adhesion kinase (FAK) and enhanced melanocyte proliferation by upregulating protein kinase B (AKT). These observations suggest the involvement of miR-379 in the physiological regulation of melanocytes, mediated by targeting IGF1R on insulin receptor (IR) compensation and subsequent crosstalk.
Subject(s)
Camelids, New World/metabolism , Melanocytes/metabolism , MicroRNAs/biosynthesis , Pigmentation , Receptor, IGF Type 1/biosynthesis , 3' Untranslated Regions , Activating Transcription Factor 2/metabolism , Animals , Cell Movement , Cell Proliferation , Melanins/metabolism , Mice , MicroRNAs/genetics , Microphthalmia-Associated Transcription Factor/metabolism , Phenotype , Polymerase Chain Reaction , Protein Binding , Receptor, Insulin/metabolismABSTRACT
Synaptotagmin-4 (SYT4) is a membrane protein that regulates membrane traffic in neurons in a calcium-dependent or calcium-independent manner. In melanocytes, the intracellular free calcium ion (Ca2+ ) may be important for dendrite growth and melanogenesis. Mammalian melanocytes originating from neural crest cells produce melanins. Therefore, we predicted that SYT4 might play a role in melanogenesis and the dendrite morphology of melanocytes. To investigate whether SYT4 is involved in melanocyte physiology, SYT4 was overexpressed in alpaca melanocytes and B16-F10 cells. The results showed that SYT4 overexpression resulted in a phenotype consistent with melanogenesis and dendrite extension. At the molecular level, SYT4 interacted with extracellular regulated MAP kinase (ERK) to decrease p-ERK activity, which negatively regulated CREB expression. Furthermore, cyclic AMP-responsive element-binding protein (CREB) was upregulated and caused the downregulation of the expression of melanogenic regulatory proteins, including microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1), dopachrome tautomerase (DCT), and transient receptor potential melastatin 1 (TRPM1). Intracellular free Ca2+ promoted the upregulation of calcium/calmodulin dependent protein kinase IV (CAMK4) expression, which phosphorylated CREB (p-CREB). In turn, p-CREB participated in the transcription of MITF. These results demonstrated that SYT4 promoted melanogenesis through dendrite extension and tyrosinase activity, during which the regulation of Ca2+ influx via the TRPM1 channel was a key factor. SIGNIFICANCE OF THE STUDY: Intracellular Ca2+ is important for the function and survival of melanocytes and melanoma cells. SYT4 stimulated melanogenesis through calcium. These results provide evidence that SYT4 regulates Ca2+ influx through TRPM1 to cause melanogenesis and axonal elongation in alpaca melanocytes and further suggesting that the growth and metastasis of melanoma is controlled by the inhibited expression of SYT4 in melanoma cells.
Subject(s)
Calcium/metabolism , Melanocytes/metabolism , Synaptotagmins/metabolism , TRPM Cation Channels/metabolism , Animals , Camelids, New World , Dendrites/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Gene Expression Regulation , MAP Kinase Signaling System , Melanins/biosynthesis , Melanoma, Experimental/metabolism , Mice , Monophenol Monooxygenase/metabolism , Neural Crest/metabolism , PigmentationABSTRACT
BACKGROUND: Current studies regarding glucocorticosteroid treatment of influenza have only estimated risk of critical illness or death which can be easily confounded by timing of treatment administration. We used severe acute respiratory infection (sARI) as an endpoint and investigated risk associated with receiving glucocorticosteroids before sARI onset. METHODS: sARI cases were defined as influenza-like illness (ILI) with pH1N1 infection and respiratory distress. Controls were defined as pH1N1 cases other than sARI and randomly selected from the community. We compared glucocorticosteroids and other medications used before sARI onset using a matched case control study adjusted for age group as well as underlying disease. Time-dependent risk and dose responses at different time periods over the course of sARI cases were also examined. RESULTS: Of the sARI cases, 34% received glucocorticosteroids before sARI onset compared to 3.8% of controls during equivalent days (ORM-H = 17,95%CI = 2.1-135). Receiving glucocorticosteroids before sARI onset increased risk of developing subsequent critical illness or death (ORM-H = 5.7,95%CI = 1.6-20.2), and the ORM-H increased from 5.7 to 8.5 for continued glucocorticosteroid use after sARI onset. However, only receiving glucocorticosteroids after sARI onset did not increase risk of severe illness (ORM-H = 1.1,95%CI = 0.3-4.6). Each increase in glucocorticosteroids dose of 1 mg/kg/day before sARI onset resulted in an increase of 0.62 (R2 = 0.87) in the pMEWS score at the time of sARI onset. CONCLUSIONS: Early glucocorticosteroid treatment increased risk of sARI and subsequent critical illness or death; however, only receiving glucocorticosteroids after sARI onset did not increase risk of severe illness.
Subject(s)
Glucocorticoids/administration & dosage , Influenza A Virus, H1N1 Subtype/physiology , Influenza, Human/drug therapy , Respiratory Tract Infections/epidemiology , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , China/epidemiology , Female , Glucocorticoids/adverse effects , Hospitalization , Humans , Influenza, Human/virology , Male , Middle Aged , Respiratory Tract Infections/etiology , Risk , Young AdultABSTRACT
Lake bathymetry provides valuable information for lake basin planning and treatment, lake watershed erosion and siltation management, water resource planning, and environmental protection. Lake bathymetry has been surveyed with sounding techniques, including single-beam and multi-beam sonar sounding, and unmanned ship sounding. Although these techniques have high accuracy, most of them require long survey cycles and entail a high degree of difficulty. On the contrary, optical remote sensing inversion methods are easy to implement, but tend to provide less accurate bathymetry measures, especially when applied to turbid waters. The present study, therefore, aims to improve the accuracy of bathymetry measurements through integrating Landsat Thematic Mapper imagery, the Ice, Cloud, and Land Elevation Satellite's Geoscience Laser Altimeter System (ICESat/GLAS) data, and water level data measured at hydrological stations. First, the boundaries of a lake at multiple dates were derived using water extraction, initial boundary extraction, and Landsat Thematic Mapper/Enhanced Thematic Mapper (TM/ETM+) strip removal processing techniques. Second, ICESat/GLAS data were introduced to obtain additional topographic information of a lake. The striped topography of a lake's area was then obtained through eliminating and correcting erroneous points and interpolating the values of unknown points. Third, the entire bathymetry of the lake was obtained through interpolating water level values of lake boundary points in various dates. Experiments show that accurate bathymetry (±1 m) can be successfully derived.
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BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by hantaviruses. Landscape can influence the risk of hantavirus infection for humans, mainly through its effect on rodent community composition and distribution. It is important to understand how landscapes influence population dynamics for different rodent species and the subsequent effect on HFRS risk. METHODS: To determine how rodent community composition influenced human hantavirus infection, we monitored rodent communities in the prefecture-level cities of Loudi and Shaoyang, China, from 2006 to 2013. Land use data were extracted from satellite images and rodent community diversity was analyzed in 45 trapping sites, in different environments. Potential contact matrices, determining how rodent community composition influence HFRS infection among different land use types, were estimated based on rodent community composition and environment type for geo-located HFRS cases. RESULTS: Apodemus agrarius and Rattus norvegicus were the predominant species in Loudi and Shaoyang, respectively. The major risk of HFRS infection was concentrated in areas with cultivated land and was associated with A. agrarius, R. norvegicus, and Rattus flavipectus. In urban areas in Shaoyang, Mus musculus was related to risk of hantavirus infection. CONCLUSIONS: Landscape features and rodent community dynamics may affect the risk of human hantavirus infection. Results of this study may be useful for the development of HFRS prevention initiatives that are customized for regions with different geographical environments.
Subject(s)
Hemorrhagic Fever with Renal Syndrome/etiology , Rodentia , Agriculture , Animals , China/epidemiology , Cities , Disease Reservoirs , Ecosystem , Environmental Monitoring/methods , Hantavirus Infections/epidemiology , Hemorrhagic Fever with Renal Syndrome/epidemiology , Humans , Mice , Rats , Risk Factors , Rural Population , Urban PopulationABSTRACT
BACKGROUND: Hand, foot and mouth disease (HFMD) is one of the highest reported infectious diseases with several outbreaks across the world. This study aimed at describing epidemiological characteristics, investigating spatio-temporal clustering changes, and identifying determinant factors in different clustering areas of HFMD. METHODS: Descriptive statistics was used to evaluate the epidemic characteristics of HFMD from 2009 to 2015. Spatial autocorrelation and spatio-temporal cluster analysis were used to explore the spatial temporal patterns. An autologistic regression model was employed to explore determinants of HFMD clustering. RESULTS: The incidence rates of HFMD ranged from 54.31/10 million to 318.06/10 million between 2009 and 2015 in Hunan. Cases were mainly prevalent in children aged 5 years and even younger, with an average male-to-female sex ratio of 1.66, and two epidemic periods in each year. Clustering areas gathered in the northern regions in 2009 and in the central regions from 2010 to 2012. They moved to central-southern regions in 2013 and 2014 and central-western regions in 2015. The significant risk factors of HFMD clusters were rainfall (OR = 2.187), temperature (OR = 4.329) and humidity (OR = 2.070). The protect factor was wind speed (OR = 0.258). CONCLUSIONS: The HFMD incidence from 2009 to 2015 in Hunan showed a new spatiotemporal clustering tendency, with the shifting trend of clustering areas toward south and west. Meteorological factors showed a strong association with HFMD clustering, which may assist in predicting future spatial-temporal clusters.
Subject(s)
Hand, Foot and Mouth Disease/epidemiology , Spatio-Temporal Analysis , Child , Child, Preschool , China/epidemiology , Cluster Analysis , Disease Outbreaks , Epidemics , Female , Humans , Humidity , Incidence , Infant , Male , Meteorological Concepts , Risk Factors , Spatial Analysis , TemperatureABSTRACT
In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus. In a mouse model, the reassortant virus, termed influenza A/Hunan/42443/2015(H1N1) virus, showed higher infectivity and virulence than another human EA-H1N1 isolate, influenza A/Jiangsu/1/2011(H1N1) virus. In the respiratory tract of mice, virus replication by influenza A/Hunan/42443/2015(H1N1) virus was substantially higher than that by influenza A/Jiangsu/1/2011(H1N1) virus. Human-to-human transmission of influenza A/Hunan/42443/2015(H1N1) virus has not been detected; however, given the circulation of novel EA-H1N1 viruses in pigs, enhanced surveillance should be instituted among swine and humans.
Subject(s)
Influenza A Virus, H1N1 Subtype/classification , Influenza A Virus, H1N1 Subtype/genetics , Influenza, Human/diagnosis , Influenza, Human/virology , Reassortant Viruses , Animals , Cell Line , China/epidemiology , Genes, Viral , History, 21st Century , Humans , Infant , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza A Virus, H1N1 Subtype/pathogenicity , Influenza, Human/epidemiology , Influenza, Human/history , Multilocus Sequence Typing , Phylogeny , RNA, Viral , Serologic Tests , Severity of Illness Index , Virulence , Virus ReplicationABSTRACT
BACKGROUND: The pandemic potential of avian influenza viruses A(H5N1) and A(H7N9) remains an unresolved but critically important question. METHODS: We compared the characteristics of sporadic and clustered cases of human H5N1 and H7N9 infection, estimated the relative risk of infection in blood-related contacts, and the reproduction number (R). RESULTS: We assembled and analyzed data on 720 H5N1 cases and 460 H7N9 cases up to 2 November 2014. The severity and average age of sporadic/index cases of H7N9 was greater than secondary cases (71% requiring intensive care unit admission vs 33%, P = .007; median age 59 years vs 31, P < .001). We observed no significant differences in the age and severity between sporadic/index and secondary H5N1 cases. The upper limit of the 95% confidence interval (CI) for R was 0.12 for H5N1 and 0.27 for H7N9. A higher proportion of H5N1 infections occurred in clusters (20%) compared to H7N9 (8%). The relative risk of infection in blood-related contacts of cases compared to unrelated contacts was 8.96 for H5N1 (95% CI, 1.30, 61.86) and 0.80 for H7N9 (95% CI, .32, 1.97). CONCLUSIONS: The results are consistent with an ascertainment bias towards severe and older cases for sporadic H7N9 but not for H5N1. The lack of evidence for ascertainment bias in sporadic H5N1 cases, the more pronounced clustering of cases, and the higher risk of infection in blood-related contacts, support the hypothesis that susceptibility to H5N1 may be limited and familial. This analysis suggests the potential pandemic risk may be greater for H7N9 than H5N1.
Subject(s)
Influenza A Virus, H5N1 Subtype/isolation & purification , Influenza A Virus, H7N9 Subtype/isolation & purification , Influenza, Human/epidemiology , Influenza, Human/virology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Animals , Basic Reproduction Number , Child , Child, Preschool , Family Health , Female , Humans , Infant , Influenza, Human/pathology , Male , Middle Aged , Risk Assessment , Severity of Illness Index , Young AdultABSTRACT
During the epidemic period of the novel H7N9 viruses, an influenza A (H9N2) virus was isolated from a 7-year-old boy with influenza-like illness in Yongzhou city of Hunan province in November 2013. To identify the possible source of infection, environmental specimens collected from local live poultry markets epidemiologically linked to the human case in Yongzhou city were tested for influenza type A and its subtypes H5, H7, and H9 using real-time RT-PCR methods as well as virus isolation, and four other H9N2 viruses were isolated. The real-time RT-PCR results showed that the environment was highly contaminated with avian influenza H9 subtype viruses (18.0%). Sequencing analyses revealed that the virus isolated from the patient, which was highly similar (98.5-99.8%) to one of isolates from environment in complete genome sequences, was of avian origin. Based on phylogenetic and antigenic analyses, it belonged to genotype S and Y280 lineage. In addition, the virus exhibited high homology (95.7-99.5%) of all six internal gene lineages with the novel H7N9 and H10N8 viruses which caused epidemic and endemic in China. Meanwhile, it carried several mammalian adapted molecular residues including Q226L in HA protein, L13P in PB1 protein, K356R, S409N in PA protein, V15I in M1 protein, I28V, L55F in M2 protein, and E227K in NS protein. These findings reinforce the significance of continuous surveillance of H9N2 influenza viruses.
Subject(s)
Influenza A Virus, H9N2 Subtype/classification , Influenza A Virus, H9N2 Subtype/isolation & purification , Influenza in Birds/epidemiology , Influenza, Human/epidemiology , Influenza, Human/virology , Animals , Child , China/epidemiology , Epidemics , Genome, Viral , Genotype , Humans , Influenza A Virus, H10N8 Subtype/genetics , Influenza A Virus, H10N8 Subtype/isolation & purification , Influenza A Virus, H7N9 Subtype/genetics , Influenza A Virus, H7N9 Subtype/isolation & purification , Influenza A Virus, H9N2 Subtype/genetics , Influenza A virus/classification , Influenza A virus/genetics , Influenza A virus/isolation & purification , Male , Phylogeny , Poultry , Real-Time Polymerase Chain Reaction , Sequence Analysis, DNA , Viral Proteins/geneticsABSTRACT
An ultra-compact rotational symmetric lens with double freeform surfaces based on the edge-ray principle is designed in this paper. The lens redistributes light emitting from a Lambertian LED light source to achieve uniform illumination within the target area. The initial design is optimized for optics compactness under structural constraints and illumination requirement using the genetic algorithm. A design for the double-freeform-surface lens with a height of the optics system h = 12.56 mm for a circular LED source with a diameter D = 10 mm is demonstrated for uniform illumination within 45° and thus achieves optics compactness h/D = 1.256, which is half of that achieved by the single-freeform-surface lens. The Monte-Carlo ray-tracing result shows an illumination circular area with a clear cut-off at R = 1000 mm at the target plane in a distance H = 1000 mm. The uniformity within the target illumination area is greater than 0.9 and the light output efficiency is as high as 0.9865.
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BACKGROUND: Wild waterfowl are recognized as the natural reservoir for influenza A viruses. Two distinct lineages, the American and Eurasian lineages, have been identified in wild birds. Gene flow between the two lineages is limited. The H9N2 virus has become prevalent in poultry throughout Eurasia, and mainly circulates in wild ducks and shorebirds in North America. METHODS: In this study, 22 H9N2 avian influenza viruses were isolated from wild waterfowl feces in East Dongting Lake Nature Reserve in November 2011 and March 2012. The phylogenetic, molecular, and antigenic characteristics of these viruses were analyzed based on analyses of the whole genome sequence of each isolate. RESULTS: Phylogenetic analyses indicated that these H9N2 viruses were generated by reassortment events. The HA, NA, PA, and NS genes were derived from the American gene pool, and the other four genes were derived from the Eurasian gene pool. Antigenic analyses indicated that these viruses were significantly different from the Eurasian lineage viruses. CONCLUSIONS: This study presents the isolation of novel intercontinental recombinant H9N2 viruses from wild waterfowl in the East Dongting Lake wetland. The novel genotype H9N2 virus has not been detected in poultry in the region yet, and may be transmitted to naïve birds in poultry farms. Therefore, our results highlight the need for ongoing surveillance of wild birds and poultry in this region.
Subject(s)
Antigens, Viral/analysis , Genome, Viral , Influenza A Virus, H9N2 Subtype/classification , Influenza A Virus, H9N2 Subtype/isolation & purification , Influenza in Birds/virology , Phylogeny , RNA, Viral/genetics , Animals , Birds , China , Evolution, Molecular , Influenza A Virus, H9N2 Subtype/genetics , Influenza A Virus, H9N2 Subtype/immunology , Lakes , Molecular Sequence Data , Reassortant Viruses/classification , Reassortant Viruses/genetics , Reassortant Viruses/immunology , Reassortant Viruses/isolation & purification , Sequence Analysis, DNA , WetlandsABSTRACT
Background: The current outbreak of novel coronavirus disease 2019 has caused a serious disease burden worldwide. Vaccines are an important factor to sustain the epidemic. Although with a relatively high-vaccination worldwide, the decay of vaccine efficacy and the arising of new variants lead us to the challenge of maintaining a sufficient immune barrier to protect the population. Method: A case-contact tracking data in Hunan, China, is used to estimate the contact pattern of cases for scenarios including school, workspace, etc, rather than ordinary susceptible population. Based on the estimated vaccine coverage and efficacy, a multi-group vaccinated-exposed-presymptomatic-symptomatic-asymptomatic-removed model (VEFIAR) with 8 age groups, with each partitioned into 4 vaccination status groups is developed. The optimal dose-wise vaccinating strategy is optimized based on the currently estimated immunity barrier of coverage and efficacy, using the greedy algorithm that minimizes the cumulative cases, population size of hospitalization and fatality respectively in a certain future interval. Parameters of Delta and Omicron variants are used respectively in the optimization. Results: The estimated contact matrices of cases showed a concentration on middle ages, and has compatible magnitudes compared to estimations from contact surveys in other studies. The VEFIAR model is numerically stable. The optimal controled vaccination strategy requires immediate vaccination on the un-vaccinated high-contact population of age 30-39 to reduce the cumulative cases, and is stable with different basic reproduction numbers ( R 0 ). As for minimizing hospitalization and fatality, the optimized strategy requires vaccination on the un-vaccinated of both aged 30-39 of high contact frequency and the vulnerable older. Conclusion: The objective of reducing transmission requires vaccination in age groups of the highest contact frequency, with more priority for un-vaccinated than un-fully or fully vaccinated. The objective of reducing total hospitalization and fatality requires not only to reduce transmission but also to protect the vulnerable older. The priority changes by vaccination progress. For any region, if the local contact pattern is available, then with the vaccination coverage, efficacy, and disease characteristics of relative risks in heterogeneous populations, the optimal dose-wise vaccinating process will be obtained and gives hints for decision-making.
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What is already known about this topic?: Little is known about the epidemiology, natural history, and transmission patterns of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant. Monitoring the evolution of viral fitness of SARS-CoV-2 in the host population is key for preparedness and response planning. What is added by this report?: We analyzed a successfully contained local outbreak of Delta that took place in Hunan, China, and provided estimates of time-to-key event periods, infectiousness over time, and risk factors for SARS-CoV-2 infection and transmission for a still poorly understood variant. What are the implications for public health practice?: Our findings simultaneously shed light on both the characteristics of the Delta variant, by identifying key age groups, risk factors, and transmission pathways, and planning a future response effort against SARS-CoV-2.
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BACKGROUND: Tuberculosis (TB) is a public health problem worldwide, and the influence of meteorological and air pollutants on the incidence of tuberculosis have been attracting interest from researchers. It is of great importance to use machine learning to build a prediction model of tuberculosis incidence influenced by meteorological and air pollutants for timely and applicable measures of both prevention and control. METHODS: The data of daily TB notifications, meteorological factors and air pollutants in Changde City, Hunan Province ranging from 2010 to 2021 were collected. Spearman rank correlation analysis was conducted to analyze the correlation between the daily TB notifications and the meteorological factors or air pollutants. Based on the correlation analysis results, machine learning methods, including support vector regression, random forest regression and a BP neural network model, were utilized to construct the incidence prediction model of tuberculosis. RMSE, MAE and MAPE were performed to evaluate the constructed model for selecting the best prediction model. RESULTS: (1) From the year 2010 to 2021, the overall incidence of tuberculosis in Changde City showed a downward trend. (2) The daily TB notifications was positively correlated with average temperature (r = 0.231), maximum temperature (r = 0.194), minimum temperature (r = 0.165), sunshine duration (r = 0.329), PM2.5 (r = 0.097), PM10 (r = 0.215) and O3 (r = 0.084) (p < 0.05). However, there was a significant negative correlation between the daily TB notifications and mean air pressure (r = -0.119), precipitation (r = -0.063), relative humidity (r = -0.084), CO (r = -0.038) and SO2 (r = -0.034) (p < 0.05). (3) The random forest regression model had the best fitting effect, while the BP neural network model exhibited the best prediction. (4) The validation set of the BP neural network model, including average daily temperature, sunshine hours and PM10, showed the lowest root mean square error, mean absolute error and mean absolute percentage error, followed by support vector regression. CONCLUSIONS: The prediction trend of the BP neural network model, including average daily temperature, sunshine hours and PM10, successfully mimics the actual incidence, and the peak incidence highly coincides with the actual aggregation time, with a high accuracy and a minimum error. Taken together, these data suggest that the BP neural network model can predict the incidence trend of tuberculosis in Changde City.
Subject(s)
Air Pollutants , Meteorological Concepts , Tuberculosis , Humans , China/epidemiology , Cities , Incidence , Tuberculosis/epidemiology , Air Pollution/statistics & numerical dataABSTRACT
PURPOSE: The crucial role of N6-methyladenosine (m6A) methylation in anti-tumor immunity and immunotherapy has been broadly depicted. However, the molecular phenotypic linkages between m6A modification pattern and immunological ecosystem are expected to be disentangled in hepatocellular carcinoma (HCC), for immunotherapeutic unresponsiveness circumvention and combination with promising drug agents. METHODS: Modification patterns of m6A methylation were qualitatively dissected according to the large-scale HCC samples profiling. We then determined the immune phenotypic linkages by systematically evaluating their tumor microenvironment composition, immune/stromal-relevant signature, immune checkpoints correlation, and prognostic value. Individual quantification of m6A methylation pattern was achieved by m6Ascore construction, intensified by longitudinal single-cell analysis of immunotherapy cohort and validated by the transcriptomic profiles of our in-hospital GDPH-HCC cohort. Candidate therapeutic agents were also screened out. RESULTS: Three distinct m6A methylation patterns were determined in high accordance with inflamed-, excluded-, and desert-immunophenotype. To be precise, Immune-inflamed high-m6Ascore group was characterized by activated immunity with favorable prognosis. Stromal activation and absence of immune cell infiltration were observed in low-m6Ascore phenotype, linked to impaired outcome. Patients with low-m6Ascore demonstrated diminished responses and clinical benefits for cohorts receiving immunotherapy. The above credible linkage between m6A methylation pattern and tumor immune microenvironment was robustly validated in our GDPH-HCC cohort. Single-cell dynamic change of m6A methylation level in exhausted CD8 T cell and fibroblast was depicted in immunotherapy cohort fore and art. Derived from m6A methylation pattern, seven potential frontline drug agents were recognized as promising choice for high-m6Ascore patients. CONCLUSION: Our work bridged the credible linkage between epigenetics and anti-tumor immunity in HCC, unraveling m6A modification pattern as immunological indicator and predictor for immunotherapy. Individualized m6Ascore facilitated strategic choices to maximize therapy-responsive possibility.