Phospholipid Bilayer Inspired Sandwich Structural Nanofibrous Membrane for Atmospheric Water Harvesting and Selective Release.

Atmospheric water harvesting (AWH) has been broadly exploited to meet the challenge of water shortage. Despite the significant achievements of AWH, the leakage of hydroscopic salt during the AWH process hinders its practical applications. Herein, inspired by the unique selective permeability of the phospholipid bilayer, a sandwich structural (hydrophobic-hydrophilic-hydrophobic) polyacrylonitrile nanofibrous membrane (San-PAN) was fabricated for AWH. The hydrophilic inner layer loaded with LiCl could capture water from the air. The hydrophobic microchannels in the outer layer could selectively allow the free transmission of gaseous water molecules but confine the hydroscopic salt solution in the hydrophilic layer, achieving continuous and recyclable water sorption/desorption. As demonstrated, the as-prepared AWH devices presented high-efficient adsorption kinetics from 1.66 to 4.08 g g-1 at 30% to 90% relative humidity. Thus, this work strengthens the understanding of the water transmission process along microchannels and provides insight into the practical applications of AWH.

Diastereoselective Synthesis of Pyrroloquinolines via N-H Functionalization of Indoles with Vinyl Sulfonium Salts.

A [2 + 4]/[1 + 2] annulation approach was successfully established to construct pyrroloquinoline-fused cyclopropane in a highly diastereoselective fashion (>20:1 dr). The tetracyclic 1,7-fused indoles were efficiently obtained from readily available starting materials under mild conditions. This methodology displays impressive substrate generality with two reaction components. The products resulting from this doubly annulative strategy are useful synthetic intermediates.

Rab7 GTPase, a direct target of miR-131-3p, limits intracellular Spiroplasma eriocheiris infection by modulating phagocytosis.

Spiroplasma eriocheiris is a kind of intracellular pathogen without cell wall and the causative agent of Chinese mitten crab Eriocheir sinensis "tremor disease", which causes significant economic losses in the crustacean aquaculture. However, little is known about the intracellular transport of this pathogen and host innate immune response to this pathogen. Rab GTPases are key regulators for endocytosis and intracellular pathogen trafficking. In this study, we showed that S. eriocheiris infection upregulated the transcription of Rab7 through the downregulation of miR-131-3p. Subsequently, both hemocytes transfected with miR-131-3p mimics and hemocytes derived from Rab7 knockdown crabs exhibited reduced phagocytic activities and increased susceptibility to S. eriocheiris infection. Additionally, Rab7 could interact with the cell shape-determining protein MreB3 of S. eriocheiris, and its overexpression promoted S. eriocheiris internalization and fusion with lysosomes, thereby limiting S. eriocheiris replication in Drosophila S2 cells. Overall, these results demonstrated that Rab7 facilitated host cell phagocytosis and interacted with MreB3 of S. eriocheiris to prevent S. eriocheiris infection. Moreover, miR-131-3p was identified as a negative regulator of this process through its targeting of Rab7. Therefore, targeting miR-131-3p might be an effective strategy for controlling S. eriocheiris in crab aquaculture.

Focusing field energy flow simulation of an azimuthally polarized Lorentz-Gaussian beam modulated by a concentric vortex phase mask.

Based on the vector diffraction theory, this paper investigated the energy flow evolution of focusing an azimuthally polarized Lorentz-Gaussian beam modulated by concentric vortex phase mask. Three concentric zones make up the concentric vortex phase mask: the center zone, middle circular zone, and outer circular zone. Each zone has an adjusted phase. The findings demonstrate that flexible transverse energy flow rings can be obtained in the focal plane and that transverse energy flows with various polygonal forms can be produced by varying the middle circular radius or phase distribution. By adjusting the phase of the center zone and outer circular zone, the normalized transverse energy flow distribution can be rotated or changed. Findings demonstrate that this technique offers a potent means of controlling the distribution and orientation of Poynting vectors and electromagnetic fields. Moreover, a series of energy flow rings are generated to facilitate the transportation of absorptive particles to predetermined positions. These phenomena may provide a new approach for particle capture and optical particle manipulation.

Identification and validation of a prognostic model for melanoma patients with 9 ferroptosis-related gene signature.

BACKGROUND: Melanoma is a highly heterogeneous and aggressive cutaneous malignancy. Ferroptosis, a new pathway of cell death depending on the intracellar iron, has been shown to be significantly associated with apoptosis of a number of tumors, including melanoma. Nevertheless, the relationship between ferroptosis-related genes (FRGs) and the melanoma patients' prognosis needs to be explored. METHODS: Download expression profiles of FRGs and clinical data from The Cancer Genome Atlas (TCGA) database. 70% data were randomly selected from the TCGA database and utilized the univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model to create a prognostic model, and the remaining 30% was used to validate the predictive power of the model. In addition, GSE65904 and GSE22153 date sets as the verification cohort to testify the predictive ability of the signature. RESULTS: We identified nine FRGs relating with melanoma patients' overall survival (OS) and established a prognostic model based on their expression. During the research, patients were divided into group of high-risk and low-risk according to the results of LASSO regression analysis. Survival time was significantly longer in the low-risk group than that of in the high-risk group (P < 0.001). Enrichment analysis of different risk groups demonstrated that the reasons for the difference were related to immune-related pathways, and the degree of immune cell infiltration in the low-risk group was significantly higher than that in the high-risk group. CONCLUSIONS: The FRG prognostic model we established can predict the prognosis of melanoma patients and may further guide subsequent treatment.

Sediminibacterium soli sp. nov., isolated from soil.

A Gram-stain-negative, facultative anaerobic strain, designated WSJ-3T, was isolated from soil. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain WSJ-3T belongs to genus Sediminibacterium and exhibits the highest sequence similarities to Sediminibacterium roseum SYL130T (97.0%), Sediminibacterium goheungense DSM 28323T (96.9%), Sediminibacterium aquarii AA5T (96.7%), and Sediminibacterium salmoneum NBRC 103935T (95.2%). The average nucleotide identity values of strain WSJ-3T/S. roseum SYL130T and strain WSJ-3T/S. goheungense DSM 28323T are 72.2% and 70.4%, respectively, and digital DNA-DNA hybridization values for these are 19.2% and 19.1%, respectively. Strain WSJ-3T has a genome size of 3.88 Mb, with a DNA G + C content of 50.1 mol% and comprises of 3263 predicted genes. A phylogenetic tree constructed using the genomic core protein coding sequences revealed that strain WSJ-3T clusters with S. roseum SYL130T. Strain WSJ-3T has menaquinone-7 as the only respiratory quinone and phosphatidylethanolamine, three unidentified phospholipids, four unidentified aminophospholipids, two unidentified aminolipids, and three unidentified lipids as the polar lipids. The major fatty acids of strain WSJ-3T are iso-C15:0, iso-C17:0 3-OH, and iso-C15:1 G. On the basis of the polyphasic results, the isolate represents a novel species of the genus Sediminibacterium, for which the name Sediminibacterium soli sp. nov. is proposed. The type strain is WSJ-3T (= KCTC 72839T = CCTCC AB 2019408T).

Larkinella punicea sp. nov., isolated from manganese mine soil.

Strain ZZJ9T is a Gram-stain-negative, rod-shaped, aerobic bacterium isolated from manganese mine soil. Strain ZZJ9T showed the highest 16S rRNA gene sequence similarities with Larkinella rosea 15J16-1T3AT (97.1%), Larkinella terrae 15J8-8T (97.0%), Larkinella knui 15J6-3T6T (96.8%), and Larkinella ripae 15J11-1T (95.3%). The genome size of strain ZZJ9T was 8.01 Mb and the DNA G+C content was 51.8 mol%. ANI values among strain ZZJ9T and Larkinella rosea 52004 T, Larkinella knui KCTC 42998T, and Larkinella terrae 52001T were 80.5%, 82.7%, and 80.5%, respectively. dDDH values among strain ZZJ9T and Larkinella rosea 52004T, Larkinella knui KCTC 42998T, and Larkinella terrae 52001T were 23.5%, 26.0%, and 23.6%, respectively. Furthermore, the genome of strain ZZJ9T contained 6302 predicted protein-coding genes and 3114 (49%) of them had classificatory functions. The major quinone of strain ZZJ9T was menaquinone-7 and the main cellular fatty acids were C16:1ω5c (39.5%), iso-C15:0 (25.6%), and iso-C17:0 3OH (11.5%). The polar lipids of strain ZZJ9T were phosphatidylethanolamine, unidentified lipid, and two unidentified aminolipids. Based on the results of phylogenetic, genome, phenotypic, and chemotaxonomic analytical, strain ZZJ9T represents a novel species of the genus Larkinella, for which the name Larkinella punicea sp. Nov. is proposed. The type strain is ZZJ9T (= KCTC 62876T = CCTCC AB 2018215T).

Runella aurantiaca sp. nov., isolated from sludge of a manganese mine.

A Gram-stain-negative, filamentous rod-shaped, aerobic and non-motile strain, YX9T, was isolated from sludge of a manganese mine. Analysis of the 16S rRNA gene sequence revealed that strain YX9T formed the same branch within the members of the genus Runella and showed high relatedness to Runella slithyformis DSM 19594T (98.1 %), Runella palustris HMF3829T (96.0 %) and Runella zeae NS12T (95.4 %). The genome length of strain YX9T was 7.21 Mb, had 5985 coding sequences and a DNA G+C content of 44.8 mol%. The average nucleotide identity value of the draft genomes between strain YX9T and R. slithyformis DSM 19594T was 80.7 %. The major fatty acids of strain YX9T were iso-C15 : 0, C16:1 ω5c and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The predominant respiratory quinone was menaquinone 7. The polar lipids of strain YX9T were phosphatidylethanolamine, four unidentified lipids, two aminolipids, a phospholipid and a glycolipid. Based on the results of genotypic and phenotypic studies, strain YX9T represents a novel species within the genus Runella, for which the name Runellaaurantiaca sp. nov. is proposed (=KCTC 62875T=CCTCC AB 2018214T).

Improving Accuracy of Jaw Reconstruction Based on Gender Differences.

PURPOSE: The aim of the present study was to redetermine the position of the key points (skeletal marker points) in the damaged female and male jaws to improve the accuracy of jaw reconstruction. MATERIALS AND METHODS: To develop a personalized jaw reconstruction guidance program for each patient, we first made 3 statistics to compare the gender differences in the jaw. Next, we proposed and compared 3 methods to use to restore the key skeletal marker points of the damaged jaw according to our statistics. RESULTS: We collected 111 groups of computed tomography data of the jaw from normal people as experimental material. The use of our statistics showed that gender differences are present in the shape of the jaw. In addition, some key angles and distances of the jaw satisfied the Gaussian distribution. The reconstruction results showed that our methods will result in better effects than the widely used method. CONCLUSIONS: To reduce errors, gender differences should be considered when designing a reconstruction approach to the jaw. In addition, our methods can improve the accuracy of reconstruction of the jaw.

Nocardioides gansuensis sp. nov., isolated from geopark soil.

A novel bacterial strain, designated WSJ-1T, was isolated from geopark soil in Gansu province, PR China. The highest 16S rRNA gene sequence similarities were to those of Nocardioides sediminis MSL-01T (97.10 %), Nocardioides aquiterrae GW-9T (97.08 %) and Nocardioides terrigena DS-17T (96.94 %). Strain WSJ-1T grouped with N. terrigena DS-17T and N. sediminis MSL-01T in 16S rRNA gene-based phylogenetic trees. The DNA-DNA relatedness of WSJ-1T/N. sediminis JCM19559T and WSJ-1T/N. aquiterrae JCM11813T were 44.8 and 29.2 %, respectively. Average nucleotide identity values of whole genome sequences of WSJ-1T/N. terrigena KCTC19217T and WSJ-1T/N. sediminis KCTC19271T were 78.83 and 78.83 %, respectively. Its genome size was 4.76 Mb, comprising 4517 predicted genes with a DNA G+C content of 70.9 %. Strain WSJ-1T contained menaquinone-8(H4) as the major respiratory quinone and ll-2,6-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylinositol. The major cellular fatty acids were iso-C16 : 0, C18 : 1ω9c and C17 : 1ω8c. Based on the polyphasic analyses, the isolate is considered to represent a novel species of the genus Nocardioides, for which the name Nocardioidesgansuensis sp. nov. is proposed. The type strain is WSJ-1T (=KCTC 49117T=CCTCC AB 2018027T).

Mucilaginibacter terrenus sp. nov., isolated from manganese mine soil.

Strain ZH6T is a Gram-stain-negative, rod-shaped, aerobic bacterium isolated from manganese mine soil. Strain ZH6T had highest 16S rRNA gene sequence similarities to Mucilaginibacter yixingensis YX-36T (96.9 %) and Mucilaginibacter psychrotolerans NH7-4T (96.8 %). The genome size of strain ZH6T was 4.61 Mb with a DNA G+C content of 44.0 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain ZH6T and M. yixingensis DSM 26809T were 70.6 and 19.2 %, respectively. Strain ZH6T had menaquinone-7 as a major quinone and main cellular fatty acids of iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The polar lipids of strain ZH6T were a phosphatidylethanolamine, an unidentified glycolipid, an unidentified phospholipid, three unidentified aminophospholipids and four unidentified lipids. Based on the phenotypic, chemotaxonomic and phylogenetic results, strain ZH6T represents a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacterterrenus sp. nov., is proposed. The type strain is ZH6T (=CCTCC AB 2018373T=KCTC 72075T).

Gene function and expression regulation of RuvRCAB in bacterial Cr(VI), As(III), Sb(III), and Cd(II) resistance.

Alishewanella sp. WH16-1 is a heavy metal-resistant bacterium. Previously, a putative YebC family regulator gene, designated ruvR, was associated with Cr(VI) resistance. In this study, comprehensive analyses were performed to study the role of ruvR and its adjunct putative DNA repairing genes, ruvCAB, in the heavy metal resistance of Alishewanella sp. WH16-1. RT-PCR analysis showed that ruvR is cotranscribed with ruvCAB. Gene mutation and complementation experiments indicated that ruvRCAB contributes to Cr(VI), As(III), Sb(III), and Cd(II) resistance in vivo. Random amplification of polymorphic DNA-PCR revealed that ruvCAB is associated with DNA repair mediated by these metals, and the presence of the metals in the cells was confirmed by elemental mapping and energy-dispersive X-ray spectrograph analysis. In addition, qRT-PCR, reporter gene assay, and in vivo and in vitro protein-DNA interaction experiments indicated that RuvR positively regulates the transcription of ruvCAB and is induced by Cr(VI). Finally, site-directed mutagenesis demonstrated that Asp103 is essential for the DNA binding ability of RuvR. The above results suggest that RuvR is involved in Cr(VI) resistance and resistance to other metals and that RuvR positively regulates the expression of ruvCAB. Based on our study and literatures, a model of RuvRCAB detailing bacterial heavy metal resistance is proposed. The RuvRCAB system plays an important role in the ability of Alishewanella sp. WH16-1 to survive in environments with heavy metals.

Role of miR-182-5p overexpression in trichloroethylene-induced abnormal cell cycle functions in human HepG2 cells.

Trichloroethylene (TCE), a widely used industrial solvent, occurs frequently in the global environment. TCE was found to induce hepatocarcinogenesis in mice and one of the underlying mechanisms was reported to involve miR-182-5p overexpression. Subsequently, miR-182-5p overexpression was shown to contribute to chemical-induced enhanced cell proliferation in mouse liver cells by targeting the gene Cited2. The aim of this study was to compare our findings in mice with those in a human hepatoma cell line HepG2. Data demonstrated that TCE at 0.1mM exerted no marked effect on human hepatoma cell line HepG2 cell migration, cell cycle, apoptosis, and DNA damage, but significantly stimulated cell proliferation rate and increased mRNA expression levels of proliferating cell nuclear antigen (PCNA), a cell proliferation biomarker. In addition, TCE enhanced miR-182-5p expression levels but lowered Cited2 mRNA expression. In summary, data showed that similar to mouse liver cells, TCE exposure also upregulated cells miR-182-5p expression and inhibited Cited2 expression in human hepatoma cell line HepG2. Our results suggest that the TCE-mediated alterations in the observed cellular functions involve interaction with miR-182-5p. It is of interest that utilization of liver cancer tissues from the Cancer Genome Atlas (TCGA) database also demonstrated that upregulated miR-182-5p expression and reduced Cited2 mRNA expression was detected suggesting that TCE-induced hepatocarcinogenesis involved processes similar to those in humans.

Urolithiasis Causes Osteoporosis in Asians: Genetic Evidence from Mendelian Randomization and Pathway Analysis.

BACKGROUND: It is an indisputable fact that patients with urolithiasis are prone to osteoporosis (OP), but the specific mechanism of their association is unclear. Previous studies have focused on the mediation of environmental factors such as diet; however, the potential of urolithiasis itself to induce OP remains uncertain. METHODS: In this study, we used data from the Japan BioBank (6,638 urolithiasis and 7,788 OP cases) to investigate the direct causal relationship and mechanism between urolithiasis and OP, applying Mendelian randomization (MR), genetic correlation analysis, colocalization, and pathway analysis. We selected ten genetic variants as instrumental variables (IVs) for urolithiasis. RESULTS: The results showed a positive association between genetically predicted urolithiasis and OP, with significant direct effects persisting after adjusting for OP-associated factors in four models. Reverse analysis revealed no significant causal effect of genetically predicted OP on urolithiasis. While genetic correlation analysis and colocalization did not find conclusive evidence, mediation analysis identified eGFR as a significant contributor. Co-risk factor analysis unveiled cardiovascular elements as common risks for both conditions. Bioanalysis implicates cytokine, metabolic, and calcium signaling pathways may bridge urolithiasis and OP, with BCAS3, DGKH, TBX2, and TBX2-AS1 identified as potential causal genes. CONCLUSIONS: In conclusion, the study establishes a direct causal link between urolithiasis and OP, independent of environmental factors. Regardless of lifestyle, urolithiasis patients should remain vigilant about the risk of OP and consider regular OP screening. The biological mechanism of urolithiasis combined with OP and related drugs still needs to be further explored.

A PadR family transcriptional repressor regulates the transcription of chromate efflux transporter in Enterobacter sp. Z1.

Chromium is a prevalent toxic heavy metal, and chromate [Cr(VI)] exhibits high mutagenicity and carcinogenicity. The presence of the Cr(VI) efflux protein ChrA has been identified in strains exhibiting resistance to Cr(VI). Nevertheless, certain strains of bacteria that are resistant to Cr(VI) lack the presence of ChrB, a known regulatory factor. Here, a PadR family transcriptional repressor, ChrN, has been identified as a regulator in the response of Enterobacter sp. Z1(CCTCC NO: M 2019147) to Cr(VI). The chrN gene is cotranscribed with the chrA gene, and the transcriptional expression of this operon is induced by Cr(VI). The binding capacity of the ChrN protein to Cr(VI) was demonstrated by both the tryptophan fluorescence assay and Ni-NTA purification assay. The interaction between ChrN and the chrAN operon promoter was validated by reporter gene assay and electrophoretic mobility shift assay. Mutation of the conserved histidine residues His14 and His50 resulted in loss of ChrN binding with the promoter of the chrAN operon. This observation implies that these residues are crucial for establishing a DNA-binding site. These findings demonstrate that ChrN functions as a transcriptional repressor, modulating the cellular response of strain Z1 to Cr(VI) exposure.

Head-to-head comparison of cone-beam breast computed tomography and mammography in the diagnosis of primary breast cancer: A systematic review and meta-analysis.

INTRODUCTION: To compare the diagnostic performance of cone-beam breast computed tomography (CBBCT) and mammography (MG) in primary breast cancer. METHODS: PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang DATA, and China Science and Technology Journal databases were searched comprehensively from inception to March 2023. Sensitivity and specificity were calculated using bivariate random-effects models, and a summary receiver operating characteristic (SROC) curve was constructed. Bivariate I2 statistics and meta-regression analyses were also performed. The differences in diagnostic performance between CBBCT and MG were analysed using Z-test statistics. Clinical utility was explored using Fagan's nomogram, and quality assessment was conducted utilising the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. RESULTS: The summary sensitivity and specificity for CBBCT in diagnosing primary breast cancer were 0.92 (95 % CI: 0.87-0.94) and 0.79 (95 % CI: 0.71-0.85), respectively, and the area under the curve (AUC) of the SROC was 0.93 (95 % CI: 0.90-0.95). For MG, the summary sensitivity and specificity were 0.77 (95 % CI: 0.69-0.83) and 0.75 (95 % CI: 0.66-0.82), respectively, with an AUC of 0.83 (95 % CI: 0.80-0.86). The Z-test revealed that the summary sensitivity of CBBCT was significantly higher than that of MG (P < 0.001). Additionally, the summary AUC of CBBCT was significantly higher than that of MG (P < 0.001). CONCLUSION: The diagnostic performance of CBBCT for primary breast cancer was better than that of MG. However, the results of both the CBBCT and MG are based on studies with small sample sizes. Further studies with larger sample sizes and more comprehensive designs are required to address this issue.

Prevalence of antibiotic resistance genes, heavy metal, and bacterial community composition in sea sediments influenced by Eriocheir sinensis breeding aquaculture.

Eriocheir sinensis is the main aquaculture species in China. With the continuous expansion of the aquaculture scale, the demand for E. sinensis seedlings was also increased. The water used in breeding has well-nourished and its discharge into the sea posed significant risks. This study sampled the wastewater discharge points of the E. sinensis seedlings in Sheyang County, Jiangsu Province, and the areas far from the discharge points that were not affected in March and May 2023, respectively. A large number of antibiotic resistance genes (ARGs) were found in the sediment of the wastewater discharge area, and the highest ARG was sulfonamide ARG-sul1 using qPCR analysis, while ARGs were almost undetectable in the areas not affected by wastewater discharge. The 16S rRNA sequence analysis results showed that the main bacterial phyla at the wastewater discharge point were Bacteroidetes, Proteobacteria, and Thermodesulfobacteria. In the control point, the main bacterial phyla were Proteobacteria, Chlorobacterium, and Thermodesulfobacteria. There were significant differences in the composition of microbial communities between the two points, and the samples at the wastewater discharge point were more clustered and had higher similarity. The correlation network and redundancy analysis indicated that the phyla Bacteroidetes, Firmicutes, and Proteobacteria at the wastewater discharge points were positively correlated with most ARGs. The wastewater discharge had no effect on heavy metals from the two points. This study sets a foundation for future research by identifying key microbial taxa as potential ARG carriers and examining the interactions between microbial communities, ARGs, and heavy metals.

Bionic Bilayer Scaffold for Synchronous Hyperthermia Therapy of Orthotopic Osteosarcoma and Osteochondral Regeneration.

Large osseous void, postsurgical neoplastic recurrence, and slow bone-cartilage repair rate raise an imperative need to develop functional scaffold in clinical osteosarcoma treatment. Herein, a bionic bilayer scaffold constituting croconaine dye-polyethylene glycol@sodium alginate hydrogel and poly(l-lactide)/hydroxyapatite polymer matrix is fabricated to simultaneously achieve a highly efficient killing of osteosarcoma and an accelerated osteochondral regeneration. First, biomimetic osteochondral structure along with adequate interfacial interaction of the bilayer scaffold provide a structural reinforcement for transverse osseointegration and osteochondral regeneration, as evidenced by upregulated specific expressions of collagen type-I, osteopontin, and runt-related transcription factor 2. Meanwhile, thermal ablation of the synthesized nanoparticles and mitochondrial dysfunction caused by continuously released hydroxyapatite induce residual tumor necrosis synergistically. To validate the capabilities of inhibiting tumor growth and promoting osteochondral regeneration of our proposed scaffold, a novel orthotopic osteosarcoma model simulating clinical treatment scenarios of bone tumors is established on rats. Based on amounts of in vitro and in vivo results, an effective killing of osteosarcoma and a suitable osteal-microenvironment modulation of such bionic bilayer composite scaffold are achieved, which provides insightful implications for photonic hyperthermia therapy against osteosarcoma and following osseous tissue regeneration.

The W195 Residue of the Newcastle Disease Virus V Protein Is Critical for Multiple Aspects of Viral Self-Regulation through Interactions between V and Nucleoproteins.

The transcription and replication of the Newcastle disease virus (NDV) strictly rely on the viral ribonucleoprotein (RNP) complex, which is composed of viral NP, P, L and RNA. However, it is not known whether other viral non-RNP proteins participate in this process for viral self-regulation. In this study, we used a minigenome (MG) system to identify the regulatory role of the viral non-RNP proteins V, M, W, F and HN. Among them, V significantly reduced MG-encoded reporter activity compared with the other proteins and inhibited the synthesis of viral mRNA and cRNA. Further, V interacted with NP. A mutation in residue W195 of V diminished V-NP interaction and inhibited inclusion body (IB) formation in NP-P-L-cotransfected cells. Furthermore, a reverse-genetics system for the highly virulent strain F48E9 was established. The mutant rF48E9-VW195R increased viral replication and apparently enhanced IB formation. In vivo experiments demonstrated that rF48E9-VW195R decreased virulence and retarded time of death. Overall, the results indicate that the V-NP interaction of the W195 mutant V decreased, which regulated viral RNA synthesis, IB formation, viral replication and pathogenicity. This study provides insight into the self-regulation of non-RNP proteins in paramyxoviruses.

Stereocontrolled Construction of Spirooxindole-Containing 5,6,7,8-Tetrahydropyrrolo[1,2-a]pyridine via Michael/Friedel-Crafts Domino Reaction Promoted by Secondary Amine-Squaramide.

An asymmetric Michael/Friedel-Crafts cascade reaction with Morita-Baylis-Hillman (MBH) nitroallylic esters and 3-pyrrolyloxindoles has been developed for the stereoselective construction of spirooxindole-containing tetrahydroindolizines. A range of tetracyclic scaffolds possessing three consecutive chiral centers, including an all-carbon quaternary stereocenter, were generated in 53-85% isolated yields with high diastereoselectivities and enantiopurities (≥3:1 dr, 50-98% ee). A newly synthesized bifunctional secondary amine/squaramide organocatalyst was demonstrated to exhibit better stereochemical control than their tertiary analogues.