Noncentrosymmetric Na6Pb3P4S16 and Centrosymmetric K2MIIP2S6 (MII = Mg and Zn) Displaying Multiple Membered-Ring Configurations and Strong Optical Anisotropy.

Three thiophosphates including noncentrosymmetric Na6Pb3P4S16 and centrosymmetric K2MIIP2S6 (MII = Mg and Zn) were successfully synthesized in vacuum-sealed silica tubes. Note that interesting multiple six membered-rings (6-MRs) including 6-NaS6-MRs and 6-KSn-MRs (n = 6 and 7) formed by A+-centered polyhedra were discovered in the structures of title thiophosphates and these MR-composed three-dimensional (3D) tunnels show great possibility to facilitate the filling of various structural blocks (such as zero-dimensional (0D) Pb3S10 trimers or one-dimensional (1D) (MIISn)n chains). Na6Pb3P4S16 exhibits the strongest nonlinear optical (NLO) response (5.4 × AgGaS2) with phase-matching (PM) behavior among the known Pb-based PM NLO sulfides, which is much larger than that of Pb3P2S8 (3.5 × AgGaS2); it was verified that such large second harmonic generation (SHG) response in Na6Pb3P4S16 can be attributed to the huge contribution of stereochemically active PbS4 units based on the SHG-density and dipole-moment calculations. Moreover, title thiophosphates show large birefringences (Δn = 0.102-0.21), which indicates that incorporation of [P2S6] dimers or polarized PbS4 units into structures provides positive benefits for the onset of strong optical anisotropy.

Characterization of avian influenza A (H4N2) viruses isolated from wild birds in Shanghai during 2019 to 2021.

The H4 subtype of avian influenza viruses has been widely distributed among wild birds. During the surveillance of the avian influenza virus in Shanghai from 2019 to 2021, a total of 4,451 samples were collected from wild birds, among which 46 H4 subtypes of avian influenza viruses were identified, accounting for 7.40% of the total positive samples. The H4 subtype viruses have a wide range of hosts, including the spot-billed duck, common teal, and other wild birds in Anseriformes. Among all H4 subtypes, the most abundant are the H4N2 viruses. To clarify the genetic characteristics of H4N2 viruses, the whole genome sequences of 20 H4N2 viruses were analyzed. Phylogenetical analysis showed that all 8 genes of these viruses belonged to the Eurasian lineage and closely clustered with low pathogenic avian influenza viruses from countries along the East Asia-Australia migratory route. However, the PB1 gene of 1 H4N2 virus (NH21920) might provide its internal gene for highly pathogenic avian influenza H5N8 viruses in Korea and Japan. At least 10 genotypes were identified in these viruses, indicating that they underwent multiple complex recombination events. Our study has provided a better epidemiological understanding of the H4N2 viruses in wild birds. Considering the mutational potential, comprehensive surveillance of the H4N2 virus in both poultry and wild birds is imperative.

Co-circulation of coronavirus and avian influenza virus in wild birds in Shanghai (2020-2021).

Co-infection of SARS-CoV-2 and influenza viruses has been reported worldwide in humans. Wild birds are natural reservoir hosts for coronaviruses (CoVs) and avian influenza viruses (AIVs). It is unknown whether co-infection with these two types of viruses occurs in wild birds. In this study, the prevalence of co-infection with CoV and AIV in wild birds in Shanghai, China during 2020-2021 was investigated by detecting these viruses in cloacal, tracheal, and faecal samples. Results showed that the overall rate of samples positive for both CoV and AIV was 3.3% (82/2510; 95% confidence interval [CI]: 2.6%-4.0%), and that was mainly from Anseriformes. In CoV-positive samples, 38.9% (82/211; 95% CI: 32.5%-45.6%) of them had both CoVs and AIVs, whereas only 26.9% (82/305; 95% CI: 22.2%-32.1%) of AIV-positive samples had both CoVs and AIVs. These results suggest that CoV infection in wild birds renders them more susceptible to AIV infection. Phylogenetic analysis based on partial RNA-dependent RNA polymerase (RdRp) gene sequences of CoVs revealed that gamma-CoVs mainly cluster with duck CoVs and that delta-CoVs are more diversified and cluster with those of various wild birds. Continual surveillance is necessity to monitor the transmission and evolution of co-infection of these two types of viruses in their natural hosts.

Pathogenicity and immunogenicity of a new strain of porcine epidemic diarrhea virus containing a novel deletion in the N gene.

Since late 2010, highly virulent PEDV G2-genotype strains have emerged globally extracting heavy losses on the pork industries of numerous countries. We investigated the characteristics of a field strain of PEDV (PEDV strain SH) isolated from a piglet with severe diarrhea on a farm in Shanghai China. Whole genome sequencing and analysis revealed that the SH strain belonged to subtype G2b and has a unique 12-aa deletion (aa 399-410) including the antigenic epitope NEP-1C9 (aa 398-406) of the N protein. PEDV SH strain is highly pathogenic to challenged newborn piglets, resulting in 100 % morbidity and mortality. Pathological examination revealed significant villus atrophy in the jejuna of infected piglets. Mice inoculated with inactivated PEDV SH produced antibodies against the N protein, but no antibodies against the deletions. These results illustrated that deletion of the NEP-1C9 epitope had no effect on the immunogenicity or pathogenicity of PEDV, providing evidence of the necessity to monitor the genetic diversity of the virus. Our study also contributes to development of candidate for vaccines and diagnostics that could differentiate pigs seropositive due to vaccination by conventional strains from wild virus infection.

Effect of raw material variability of glipizide on the in vitro dissolution rate and in vivo bioavailability performance: The importance of particle size.

The objective of this study was to understand the impact of active pharmaceutical ingredients (API) particle size on a re-developed generic product of glipizide and to improve its formulation so that it exhibits bioequivalent to that of the reference listed drug (RLD). Two commercial batches of APIs (API-1 and API-2) with the same polymorphism and one batch of home-made APIs (API-3) with super-small particle size were used in the present study. The in vitro dissolution profiles of the tested formulations were compared with the RLD in a series of dissolution media. Then, the impact of particle size on in vivo absorption was evaluated in Beagle dogs. Compared with the RLD, formulation A with larger API size showed slower dissolution in pH 6.0 and 7.4 medium, resulting bioinequivalent with the RLD. Conversely, formulation B with smaller API size demonstrated similar in vitro dissolution profiles with the RLD and thus exhibited bioequivalent in the present study. Furthermore, formulation C with super small particle size still exhibited identical oral absorption although rapid dissolution was observed in the tested condition. Herein, it indicated that 2-5 µm might be defined as the "inert size range" of glipizide for ensuring the bioequivalence with the RLD. The results in the present study might help to obtain a better understanding of the variability in raw materials for oral absorption, develop a bioequivalent product and thus post-market quality control.

Evaluating bioequivalence of meloxicam tablets: is in-vitro dissolution test overdiscriminating?

OBJECTIVES: The aim of the study was to assess the impact of the differences in dissolution profiles of meloxicam tablets on the in-vivo bioavailability parameters after oral administration. METHODS: Compare in-vitro dissolution testing in the recommended media to evaluate in-vivo bioequivalence outcomes for the Biopharmaceutics Classification System Class II weak acidic drugs. Nine Beagle dogs received a single oral administration of each formulation (7.5 mg) in a three-way crossover design. KEY FINDINGS: The dissolution of meloxicam from both test products showed marked differences with that from the reference tablet in pH 1.0, 4.5 and 6.8 media at 50 or 75 rpm. Both formulations exhibiting slow or fast dissolution were then compared with the reference product for in-vivo bioequivalence study. Both products were bioequivalent with the reference tablet in either extent or rate of oral absorption. It indicated that the dissolution profiles which discriminated between the formulations in vitro did not accurately predict the in-vivo bioequivalence outcomes. CONCLUSIONS: Comparative dissolution profiles using similarity factor (f2 ) in the recommended media should be relaxed to fulfil the requirements for the development, scale-up and postapproval changes to immediate release oral solid dosage forms of meloxicam.

The effect of cephalexin in influencing the pharmacokinetics of a novel drug - 5'-valyl-cytarabine hydrochloride.

The aim of this study is to investigate the pharmacokinetics of 5'-valyl-cytarabine hydrochloride (OPC) when co-administered with cephalexin, which are both the substrates of PepT1. The drugs were administered orally by gavage. Blood samples were collected from the orbital plexus of the rats after oral administration of drug solutions. A new high-performance liquid chromatographic method was validated and used for determination of the two drugs. Pharmacokinetic parameters were calculated using DAS 2.1.1 software with noncompartmental analysis. After oral administration of OPC and co-administration of OPC and cephalexin, there were significant differences in the main pharmacokinetic parameters. The main pharmacokinetic parameters for the OPC group and the co-administrative group were as follows: AUC0-10 (18,168.7 ± 2561.4) ng⋅h/ml and (13,448.5 ± 2544.73) ng⋅h/ml, AUC0-∞ (18,683.1 ± 3066.5) ng⋅h/ml and (13,721.1 ± 2683.0) ng⋅h/ml, C max (6654.8 ± 481.3) ng/ml and (4765.1 ± 928.9) ng/ml, respectively. The results showed that the bioavailability of OPC could be reduced when co-administered with cephalexin, suggesting that the efficacy of a novel drug might be reduced when it came to combination use of ß-lactam antibiotics.