SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape.

The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed. Notably, the susceptibility of the 501Y.V2 variants to 12 of 17 neutralizing monoclonal antibodies was substantially diminished, and the neutralization ability of the sera from convalescent patients and immunized mice was also reduced for these variants. The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of spike. The enhanced infectivity in murine ACE2-overexpressing cells suggests the possibility of spillover of the 501Y.V2 variants to mice. Moreover, the neutralization resistance we detected for the 501Y.V2 variants suggests the potential for compromised efficacy of monoclonal antibodies and vaccines.

Comparative Genomic Analysis of PEBP Genes in Cucurbits Explores the Interactors of Cucumber CsPEBPs Related to Flowering Time.

The family of phosphatidylethanolamine-binding proteins (PEBPs) participates in various plant biological processes, mainly flowering regulation and seed germination. In cucurbit crops, several PEBP genes have been recognized to be responsible for flowering time. However, the investigation of PEBP family members across the genomes of cucurbit species has not been reported, and their conservation and divergence in structure and function remain largely unclear. Herein, PEBP genes were identified from seven cucurbit crops and were used to perform a comparative genomics analysis. The cucurbit PEBP proteins could be classified into MFT, FT, TFL, and PEBP clades, and further, the TFL clade was divided into BFT-like, CEN-like, and TFL1-like subclades. The MFT-like, FT-like, and TFL-like proteins were clearly distinguished by a critical amino acid residue at the 85th position of the Arabidopsis FT protein. In gene expression analysis, CsaPEBP1 was highly expressed in flowers, and its expression levels in females and males were 70.5 and 89.2 times higher, respectively, than those in leaves. CsaPEBP5, CsaPEBP6, and CsaPEBP7 were specifically expressed in male flowers, with expression levels 58.1, 17.3, and 15.7 times higher, respectively, than those of leaves. At least five CsaPEBP genes exhibited the highest expression during the later stages of corolla opening. Through clustering of time-series-based RNA-seq data, several potential transcription factors (TFs) interacting with four CsaPEBPs were identified during cucumber corolla opening. Because of the tandem repeats of binding sites in promoters, NF-YB (Csa4G037610) and GATA (Csa7G64580) TFs appeared to be better able to regulate the CsaPEBP2 and CsaPEBP5 genes, respectively. This study would provide helpful information for further investigating the roles of PEBP genes and their interacting TFs in growth and development processes, such as flowering time regulation in cucurbit crops.

Hydrogen bond network dynamics of heavy water resolved by alcohol hydration under an intense laser.

Despite a great deal of effort spanning for decades, it remains yet puzzling concerning how alcohol molecules functionalize the hydrogen bond (H-bond) networks of water. We employed an isotopic substitution method (using alcohol-heavy water system) to avoid spectral overlap between the alcohol hydroxyl groups and water hydrogen bonds. We showed spectrometrically that under the strong pulse laser, the low mixing ratio (VA < 20%) of alcohol can strengthen the H-bond network structure of D2O through :ÖC2H6↔ D2Ö: compression. But when VA > 20%, H-bond network of D2O will deform via the self-association between alcohol molecules. Our experiments not only reveal the H-bond kinetics of heavy water-alcohol interactions but also provide important reference for understanding the distinctive properties of H-bond in water-organic system.

Temperature dependence of stimulated Raman scattering from a VYO4 crystal.

The microstructural, electrical, and optical properties of crystals are critical to laser device performance, and the temperature-dependence effect of crystals has gained a great deal of attention in research. The linewidth, stimulated Raman scattering (SRS) shift, and intensity of the characteristic peak at 890 cm-1 of YVO4 crystal have been investigated between 148 and 448 K. As the crystal temperature increases, the bond length increases and the crystal force constant decreases, and the phonon softening process arises in the crystal at high temperature. The temperature effect on Raman shift and full width at half maximum is explained in detail in terms of the phonon anharmonic effect. The temperature dependence of SRS can be well demonstrated by an empirical equation. This work can provide new insights into the further understanding of lattice anharmonicity and contribute to the discovery of new optoelectronic materials.

Enhancement of stimulated Raman scattering of a weak vibration mode in tetrahydrofuran through the energy-transfer resonance of lycopene.

A method of energy-transfer resonance of lycopene used to enhance stimulated Raman scattering (SRS) of a weak vibration C-O mode in tetrahydrofuran (THF) was developed in this study. Only C-H SRS was observed in pure THF at high energies. When lycopene was added, the C-O SRS located at 915 cm-1 of the weak vibration mode in THF was observed. The maximum SRS enhancement of the C-O mode was achieved when the concentration was 3.72 × 10-6 mol/L because of the resonance enhancement of the solute, which transferred the excess vibrational energy to the solvent. Moreover, the pulse width compression phenomenon of the C-H vibration in the presence of C-O SRS was obtained.

Horizontal inequity trends of health care utilization in rural China after the medicine and healthcare system reform: based on longitudinal data from 2010 to 2018.

BACKGROUND: To assess the effectiveness of China's medicine and health care reform in promoting equity in health care utilization among rural residents, it is necessary to analyze temporal trends in equity in health care utilization among rural residents in China. This study is the first to assess horizontal inequity trends in health care utilization among rural Chinese residents from 2010 to 2018 and provides evidence for improving government health policies. METHODS: Longitudinal data obtained from China Family Panel Studies from 2010 to 2018 were used to determine trends in outpatient and inpatient utilization. Concentration index, concentration curve, and horizontal inequity index were calculated to measure inequalities. Decomposition analysis was applied to measure the contribution of need and non-need factors to the unfairness. RESULTS: From 2010 to 2018, outpatient utilization among rural residents increased by 35.10%, while inpatient utilization increased by 80.68%. Concentration indices for health care utilization were negative in all years. In 2012, there was an increase in the concentration index for outpatient utilization (CI = -0.0219). The concentration index for inpatient utilization decreased from -0.0478 in 2010 to -0.0888 in 2018. Except for outpatient utilization in 2012 (HI = 0.0214), horizontal inequity indices for outpatient utilization were negative in all years. The horizontal inequity index for inpatient utilization was highest in 2010 (HI = -0.0068) and lowest in 2018 (HI = -0.0303). The contribution of need factors to the inequity exceeded 50% in all years. CONCLUSIONS: Between 2010 and 2018, low-income groups in rural China used more health services. This seemingly pro-poor income-related inequality was due in large part to the greater health care need among low-income groups. Government policies aimed at increasing access to health services, particularly primary health care had helped to make health care utilization in rural China more equitable. It is necessary to design better health policies for disadvantaged groups to reduce future inequities in the use of health services by rural populations.

Infectivity and antigenicity of pseudoviruses with high-frequency mutations of SARS-CoV-2 identified in Portugal.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a major impact on global human health. During the spread of SARS-CoV-2, weakened host immunity and the use of vaccines with low efficacy may result in the development of more-virulent strains or strains with resistance to existing vaccines and antibodies. The prevalence of SARS-CoV-2 mutant strains differs between regions, and this variation may have an impact on the effectiveness of vaccines. In this study, an epidemiological investigation of SARS-CoV-2 in Portugal was performed, and the VSV-ΔG-G* pseudovirus system was used to construct 12 spike protein epidemic mutants, D614G, A222V+D614G, B.1.1.7, S477N+D614G, P1162R+D614G+A222V, D839Y+D614G, L176F+D614G, B.1.1.7+L216F, B.1.1.7+M740V, B.1.258, B.1.258+L1063F, and B.1.258+N751Y. The mutant pseudoviruses were used to infect four susceptible cell lines (Huh7, hACE2-293T-293T, Vero, and LLC-MK2) and 14 cell lines overexpressing ACE2 from different species. Mutant strains did not show increased infectivity or cross-species transmission. Neutralization activity against these pseudoviruses was evaluated using mouse serum and 11 monoclonal antibodies. The neutralizing activity of immunized mouse serum was not significantly reduced with the mutant strains, but the mutant strains from Portugal could evade nine of the 11 monoclonal antibodies tested. Neutralization resistance was mainly caused by the mutations S477N, N439K, and N501Y in the spike-receptor binding domain. These findings emphasize the importance of SARS-CoV-2 mutation tracking in different regions for epidemic prevention and control.

The influence of cross-regional medical treatment on total medical expenses, medical insurance payments, and out-of-pocket expenses of patients with malignant tumors in Chinese low-income areas.

BACKGROUND: In recent years, due to the increasing number of cross-regional medical patients, countries around the world have issued a series of policies or regulations to reduce their out-of-pocket burden. In this context, this study intended to explore the impact of the Spatio-temporal characteristics of cross-regional medical treatment on total medical expenses, medical insurance payments, and out-of-pocket expenses of patients with malignant tumors in low-income areas. METHODS: This study included 54,904 data of cross-provincial medical treatment of malignant tumor patients insured in Heilongjiang Province, China in 2020. Firstly, Microsoft Excel 2019 and ArcGIS 10.2 were applied to conduct a descriptive analysis of the Spatio-temporal characteristics of their cross-provincial medical treatment. Then, binary and multivariate logistic regression models were used to explore the specific impact of economic level and geographical distance of medical regions on total medical expenses, medical insurance payments, and out-of-pocket expenses. RESULTS: The number of cross-regional medical patients showed a gradual upward trend from February to December, and fell back in January. They were concentrated in regions with high economic level and short distance from the insured region, where were more likely to form the group with high out-of-pocket expenses (AOR = 3.620, P < 0.001; AOR = 1.882, P < 0.001). While this possibility in middle-distance medical regions were less (AOR = 0.545, P < 0.001). Afterwards, two sensitivity analysis methods showed that the results were robust. CONCLUSION: The number of cross-regional medical patients with malignant tumors in low-income areas is affected by seasonal factors, meanwhile, their total medical expenses, actual medical insurance payment levels, and out-of-pocket expenses are all affected by the economic level and geographical distance of medical regions. And the middle-distance medical regions may be the best choice for patients with planned cross-regional medical treatment. These provide some evidence for policymakers to improve the fairness and sustainability of medical security for cross-regional medical patients and reduce their direct economic burden of disease.

Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft.

Nonsyndromic orofacial cleft (NSOFC) is a severe birth defect that occurs early in embryonic development and includes the subtypes cleft palate only (CPO), cleft lip only (CLO) and cleft lip with cleft palate (CLP). Given a lack of specific genetic factor analysis for CPO and CLO, the present study aimed to dissect the landscape of genetic factors underlying the pathogenesis of these two subtypes using 6,986 cases and 10,165 controls. By combining a genome-wide association study (GWAS) for specific subtypes of CPO and CLO, as well as functional gene network and ontology pathway analysis, we identified 18 genes/loci that surpassed genome-wide significance (P < 5 × 10-8) responsible for NSOFC, including nine for CPO, seven for CLO, two for both conditions and four that contribute to the CLP subtype. Among these 18 genes/loci, 14 are novel and identified in this study and 12 contain developmental transcription factors (TFs), suggesting that TFs are the key factors for the pathogenesis of NSOFC subtypes. Interestingly, we observed an opposite effect of the genetic variants in the IRF6 gene for CPO and CLO. Moreover, the gene expression dosage effect of IRF6 with two different alleles at the same single-nucleotide polymorphism (SNP) plays important roles in driving CPO or CLO. In addition, PAX9 is a key TF for CPO. Our findings define subtypes of NSOFC using genetic factors and their functional ontologies and provide a clue to improve their diagnosis and treatment in the future.

[Prenatal diagnosis and genetic analysis of a fetus with Cornelia de Lange syndrome type 1 due to a splicing variant of NIPBL gene].

OBJECTIVE: To explore the genetic etiology of a fetus with Cornelia de Lange syndrome type 1. METHODS: Clinical data of the fetus was collected. Genomic DNA was extracted from amniotic fluid and peripheral blood samples of the parents and subjected to low-depth copy number variant sequencing, whole exome sequencing (WES) and Sanger sequencing. Pathogenicity of the candidate variant was predicted based on the guidelines of American College of Medical Genetics and Genomics (ACMG). Minigene assay was used to assess the effect of the variant on mRNA splicing. RESULTS: WES revealed that the fetus has harbored a heterozygous c.5808+5gG>A variant in the intron of the NIPBL gene, which was predicted to affect the mRNA splicing. The same variant was not detected in either parent. The variant was not recorded in ExAC, 1000G and dbSNP databases. Comprehensive analysis showed that the variant was deleterious and may result in skipping of exon 31 during mRNA splicing. CONCLUSION: The fetus was diagnosed with Cornelia de Lange syndrome type 1. Splicing variant identified by WES may be verified by minigene assay in vitro, which can provide more evidence for the prediction of its pathogenicity.

Polyketone metabolites isolated from Rhodiola tibetica endohytic fungus Alternaria sp. HJT-Y7 and their SARS-CoV-2 virus inhibitory activitives.

Six new polyketone metabolites, compounds (1-6) and seven known polyketone compounds (7-13) were isolated from Rhodiola tibetica endophytic fungus Alternaria sp. The structural elucidation of five new polyketone metabolites were elucidated on the basis of spectroscopic including 2D NMR and HRMS and spectrometric analysis. Inhibition rate evaluation revealed that compounds 1(EC50 = 0.02 mM), 3(EC50 = 0.3 mM), 6(EC50 = 0.07 mM), 8(EC50 = 0.1 mM) and 9(EC50 = 0.04 mM) had inhibitory effect on the SARS-CoV-2 virus.

A Highly Sensitive and Selective ppb-Level Acetone Sensor Based on a Pt-Doped 3D Porous SnO2 Hierarchical Structure.

In view of the low sensitivity, high operating temperature and poor selectivity of acetone measurements, in this paper much effort has been paid to improve the performance of acetone sensors from three aspects: increasing the surface area of the material, improving the surface activity and enhancing gas diffusion. A hierarchical flower-like Pt-doped (1 wt %) 3D porous SnO2 (3DPS) material was synthesized by a one-step hydrothermal method. The micropores of the material were constructed by subsequent annealing. The results of the experiments show that the 3DPS-based sensor's response is strongly dependent on temperature, exhibiting a mountain-like response curve. The maximum sensor sensitivity (Ra/Rg) was found to be as high as 505.7 at a heating temperature of 153 °C and with an exposure to 100 ppm acetone. Additionally, at 153 °C, the sensor still had a response of 2.1 when exposed to 50 ppb acetone gas. The 3DPS-based sensor also has an excellent selectivity for acetone detection. The high sensitivity can be explained by the increase in the specific surface area brought about by the hierarchical flower-like structure, the enhanced surface activity of the noble metal nanoparticles, and the rapid diffusion of free-gas and adsorbed gas molecules caused by the multiple channels of the microporous structure.

Redistribution of PM2.5 -associated nitrate and ammonium during outdoor-to-indoor transport.

Nitrate and ammonium ions are major constituents of outdoor PM2.5 . Human exposure to these ions occurs primarily indoors. To assess the adverse outcomes from exposure to them, it is necessary to quantify the relationships between outdoor and indoor PM2.5 nitrate and ammonium. The relationships for the two semi-volatile ions are more complex than those of non-volatile PM2.5 constituents (eg, sulfate, elemental carbon). This study presents a mechanistic description of their outdoor-indoor relationships that incorporates a dynamic gas-particle partitioning and key parameters such as the pH and water content of PM2.5 . Compared to measurements of nitrate and ammonium, the model has normalized mean biases of -9% and -42% and correlation coefficients of 0.95 and 0.68 for nitrate and ammonium, respectively. This suggests satisfactory agreement for nitrate, but less strong for ammonium. Sensitivity analysis on key parameters indicates that the model generally works well across a range of values typical of indoor settings. The model's performance is sensitive to pH and water content in PM2.5 , which control the gas-particle partitioning process. Indoor PM2.5 tends to be more acidic than outdoor PM2.5 , raising potential health concern. The model provides insights in exposure assessment, source apportionment, and health-composition attribution of indoor PM2.5 .

Plectin protects podocytes from adriamycin-induced apoptosis and F-actin cytoskeletal disruption through the integrin α6ß4/FAK/p38 MAPK pathway.

Podocyte injury is an early pathological change characteristic of various glomerular diseases, and apoptosis and F-actin cytoskeletal disruption are typical features of podocyte injury. In this study, we found that adriamycin (ADR) treatment resulted in typical podocyte injury and repressed plectin expression. Restoring plectin expression protected against ADR-induced podocyte injury whereas siRNA-mediated plectin silencing produced similar effects as ADR-induced podocyte injury, suggesting that plectin plays a key role in preventing podocyte injury. Further analysis showed that plectin repression induced significant integrin α6ß4, focal adhesion kinase (FAK) and p38 MAPK phosphorylation. Mutating Y1494, a key tyrosine residue in the integrin ß4 subunit, blocked FAK and p38 phosphorylation, thereby alleviating podocyte injury. Inhibitor studies demonstrated that FAK Y397 phosphorylation promoted p38 activation, resulting in podocyte apoptosis and F-actin cytoskeletal disruption. In vivo studies showed that administration of ADR to rats resulted in significantly increased 24-hour urine protein levels along with decreased plectin expression and activated integrin α6ß4, FAK, and p38. Taken together, these findings indicated that plectin protects podocytes from ADR-induced apoptosis and F-actin cytoskeletal disruption by inhibiting integrin α6ß4/FAK/p38 pathway activation and that plectin may be a therapeutic target for podocyte injury-related glomerular diseases.

Cadmium Exposure-Sedum alfredii Planting Interactions Shape the Bacterial Community in the Hyperaccumulator Plant Rhizosphere.

Rhizospheric bacteria play important roles in plant tolerance and activation of heavy metals. Understanding the bacterial rhizobiome of hyperaccumulators may contribute to the development of optimized phytoextraction for metal-polluted soils. We used 16S rRNA gene amplicon sequencing to investigate the rhizospheric bacterial communities of the cadmium (Cd) hyperaccumulating ecotype (HE) Sedum alfredii in comparison to its nonhyperaccumulating ecotype (NHE). Both planting of two ecotypes of S. alfredii and elevated Cd levels significantly decreased bacterial alpha-diversity and altered bacterial community structure in soils. The HE rhizosphere harbored a unique bacterial community differing from those in its bulk soil and NHE counterparts. Several key taxa from Actinobacteria, Bacteroidetes, and TM7 were especially abundant in HE rhizospheres under high Cd stress. The actinobacterial genus Streptomyces was responsible for the majority of the divergence of bacterial community composition between the HE rhizosphere and other soil samples. In the HE rhizosphere, the abundance of Streptomyces was 3.31- to 16.45-fold higher than that in other samples under high Cd stress. These results suggested that both the presence of the hyperaccumulator S. alfredii and Cd exposure select for a specialized rhizosphere bacterial community during phytoextraction of Cd-contaminated soils and that key taxa, such as the species affiliated with the genus Streptomyces, may play an important role in metal hyperaccumulation.IMPORTANCESedum alfredii is a well-known Cd hyperaccumulator native to China. Its potential for extracting Cd relies not only on its powerful uptake, translocation, and tolerance for Cd but also on processes underground (especially rhizosphere microbes) that facilitate root uptake and tolerance of the metal. In this study, a high-throughput sequencing approach was applied to gain insight into the soil-plant-microbe interactions that may influence Cd accumulation in the hyperaccumulator S. alfredii Here, we report the investigation of rhizosphere bacterial communities of S. alfredii in phytoremediation of different levels of Cd contamination in soils. Moreover, some key taxa in its rhizosphere identified in the study, such as the species affiliated with genus Streptomyces, may shed new light on the involvement of bacteria in phytoextraction of contaminated soils and provide new materials for phytoremediation optimization.

Calcium Deficiency Triggers Phloem Remobilization of Cadmium in a Hyperaccumulating Species.

Understanding cadmium (Cd) accumulation in plants is critical for the development of plant-based strategies for soil remediation and crop safety. Sedum alfredii is a nonbrassica plant species known to hyperaccumulate Cd. The characteristics of Cd uptake, distribution, and retranslocation affected by the Ca status were investigated at cellular levels in S. alfredii Low Ca supply significantly increased Cd contents in shoots of S. alfredii, particularly in the young leaves. Micro x-ray fluorescence images confirmed that sequestration of Cd was greatly enhanced in the young leaves under Ca deficiency stress, with a significant amount of Cd localized in mesophyll cells, compared to the young leaves supplied with high Ca levels. Cd influx into protoplasts isolated from young leaves was significantly inhibited by the addition of Ca channel inhibitors, but not by pre-exposure to Ca deficiency. In stems, the Cd signal in vascular systems under low Ca levels was 10-fold higher than in those treated with higher Ca levels. A detailed investigation of vascular bundles revealed that an extremely high Cd signal induced by low Ca supply occurred in the phloem tissues, but not in the xylem tissues. Transfer of Cd pretreated plants to nutrient solutions at different Ca levels confirmed that a much higher amount of Cd was reallocated to the new growth tissues under low Ca stress compared to plants supplied with sufficient Ca. These results suggest that Ca deficiency triggered a highly efficient phloem remobilization of Cd in S. alfredii and subsequently enhanced Cd accumulation in its young leaves.

Uptake, sequestration and tolerance of cadmium at cellular levels in the hyperaccumulator plant species Sedum alfredii.

Sedum alfredii is one of a few plant species known to hyperaccumulate cadmium (Cd). Uptake, localization, and tolerance of Cd at cellular levels in shoots were compared in hyperaccumulating (HE) and non-hyperaccumulating (NHE) ecotypes of Sedum alfredii. X-ray fluorescence images of Cd in stems and leaves showed only a slight Cd signal restricted within vascular bundles in the NHEs, while enhanced localization of Cd, with significant tissue- and age-dependent variations, was detected in HEs. In contrast to the vascular-enriched Cd in young stems, parenchyma cells in leaf mesophyll, stem pith and cortex tissues served as terminal storage sites for Cd sequestration in HEs. Kinetics of Cd transport into individual leaf protoplasts of the two ecotypes showed little difference in Cd accumulation. However, far more efficient storage of Cd in vacuoles was apparent in HEs. Subsequent analysis of cell viability and hydrogen peroxide levels suggested that HE protoplasts exhibited higher resistance to Cd than those of NHE protoplasts. These results suggest that efficient sequestration into vacuoles, as opposed to rapid transport into parenchyma cells, is a pivotal process in Cd accumulation and homeostasis in shoots of HE S. alfredii. This is in addition to its efficient root-to-shoot translocation of Cd.

Unique Rhizosphere Micro-characteristics Facilitate Phytoextraction of Multiple Metals in Soil by the Hyperaccumulating Plant Sedum alfredii.

Understanding the strategies that the roots of hyperaccumulating plants use to extract heavy metals from soils is important for optimizing phytoremediation. The rhizosphere characteristics of Sedum alfredii, a hyperaccumulator, were investigated 6 months after it had been planted in weathered field soils contaminated with 5.8 µg of Cd g-1, 1985.1 µg of Zn g-1, 667.5 µg of Pb g-1, and 698.8 µg of Cu g-1. In contrast with the non-hyperaccumulating ecotype (NHE), the hyperaccumulating ecotype (HE) of S. alfredii was more tolerant to the metals, and higher levels of Cd and Zn accumulated. The HE was characterized by a unique rhizosphere, including extensive root systems, a reduced soil pH, a higher metal bioavailability, and increased rhizomicrobial activity. The bioavailability of metals was significantly correlated with the HE's unique bacterial communities (P < 0.005). The HE harbored abundant Streptomyces (9.43%, family Streptomycetaceae), Kribbella (1.08%, family Nocardioidaceae), and an unclassified genus (1.09%, family Nocardioidaceae) in its rhizosphere, a composition that differed from that of the NHE. PICRUSt analysis predicted high relative abundances of imputed functional profiles in the HE rhizosphere related to membrane transport and amino acid metabolism. This study reveals the rhizosphere characteristics, particularly the unique bacterial rhizobiome of a hyperaccumulator, that might provide a new approach to facilitating heavy metal phytoextraction.

Design, Synthesis and Antiproliferative Evaluation of Novel Disulfides Containing 1,3,4-Thiadiazole Moiety.

A series of novel disulfides containing 1,3,4-thiadiazole moiety were designed, synthesized, and the structures of all products were identified by spectral data (IR, NMR, and high resolution (HR)-MS). Their in vitro antiproliferative activities were evaluated using 2-(2-methoxy-4-nitro-phenyl)-3-(4-nitro-phenyl)-5-(2,4-disulfopheyl)-2H-tetrazolium monosodium salt (CCK-8) assay against human cancer cell lines, A549 (human lung cancer cell), HeLa (human cervical cancer cell), SMMC-7721 (human liver cancer cell) and normal cell lines L929. The bioassay results indicated that most of the tested compounds 6a-k, 7a-k and 8a-k exhibited antiproliferation with different degrees, and some compounds showed better effects than positive control 5-fluorouracil (5-FU) against various cancer cell lines. Among these compounds, compound 6e exhibited the most potent inhibitory activity against A549 cells with IC50 value of 3.62 µM. Compounds 6i, 7a, 7g, 8a and 8b showed significantly antiproliferative activities against HeLa cells with IC50 values of 3.88, 3.76, 3.59, 3.38 and 3.12 µM, respectively. Compounds 6a, 7a and 8a owned high antiproliferative activities against SMMC-7721 cells with IC50 values of 2.54, 2.69 and 2.31 µM, respectively. Furthermore, all of the tested compounds showed weak cytotoxic effect against the normal cell lines L929. Based on the preliminary results, the substituent groups are vital for improving the potency and selectivity of this class of compounds.

Molecular characterization of a Class I Newcastle disease virus strain isolated from a pigeon in China.

Constant monitoring is performed to elucidate the role of natural hosts in the ecology of Newcastle disease virus (NDV). In this study, an NDV strain isolated from an asymptomatic pigeon was sequenced and analysed. Results showed that the full-length genomes of this isolate were 15,198 nucleotides with the gene order of 3'-NP-P-M-F-HN-L-5'. This NDV isolate was lentogenic, with an intracerebral pathogenicity index of 0.00 and a mean time of death more than 148 h. The isolate possessed a motif of -(112)E-R-Q-E-R-L(117)- at the F protein cleavage site. In addition, 7 and 13 amino acid substitutions were identified in the functional domains of fusion protein (F) and haemagglutinin-neuraminidase protein (HN) proteins, respectively. Analysis of the amino acids of neutralizing epitopes of F and HN proteins showed 3 and 10 amino acid substitutions, respectively, in the isolate. Phylogenetic analysis classified the isolate into genotype Ib in Class I. This isolate shared high homologies with the NDV strains isolated from wild birds and waterfowl in southern and eastern parts of China from 2005 to 2013. To our knowledge, this study is the first to report a NDV strain isolated from pigeon that belongs to genotype Ib in Class I, rather than to the traditional genotype VI or other sub-genotypes in Class II. This study provides information to elucidate the distribution and evolution of Class I viruses for further NDV prevention.