Construction of novel Ag(0)-containing silver nanoclusters by regulating auxiliary phosphine ligands.

Controlled synthesis of metal clusters through minor changes in surface ligands holds significant interest because the corresponding entities serve as ideal models for investigating the ligand environment's stereochemical and electronic contributions that impact the corresponding structures and properties of metal clusters. In this work, we obtained two Ag(0)-containing nanoclusters (Ag17 and Ag32) with near-infrared emissions by regulating phosphine auxiliary ligands. Ag17 and Ag32 bear similar shells wherein Ag17 features a trigonal bipyramid Ag5 kernel while Ag32 has a bi-icosahedral interpenetrating an Ag20 kernel. Ag17 and Ag32 showed a near-infrared emission (NIR) of around 830 nm. Benefiting from the rigid structure, Ag17 displayed a more intense near-infrared emission than Ag32. This work provides new insight into the construction of novel superatomic silver nanoclusters by regulating phosphine ligands.

Zika virus RNA structure controls its unique neurotropism by bipartite binding to Musashi-1.

Human RNA binding protein Musashi-1 (MSI1) plays a critical role in neural progenitor cells (NPCs) by binding to various host RNA transcripts. The canonical MSI1 binding site (MBS), A/GU(1-3)AG single-strand motif, is present in many RNA virus genomes, but only Zika virus (ZIKV) genome has been demonstrated to bind MSI1. Herein, we identified the AUAG motif and the AGAA tetraloop in the Xrn1-resistant RNA 2 (xrRNA2) as the canonical and non-canonical MBS, respectively, and both are crucial for ZIKV neurotropism. More importantly, the unique AGNN-type tetraloop is evolutionally conserved, and distinguishes ZIKV from other known viruses with putative MBSs. Integrated structural analysis showed that MSI1 binds to the AUAG motif and AGAA tetraloop of ZIKV in a bipartite fashion. Thus, our results not only identified an unusual viral RNA structure responsible for MSI recognition, but also revealed a role for the highly structured xrRNA in controlling viral neurotropism.

Aerosolized Zika virus infection in Guinea pigs.

Zika virus (ZIKV) is primarily transmitted through mosquito bites and sexual contact, and vertical transmission of ZIKV has also been observed in humans. In addition, ZIKV infection via unknown transmission routes has been frequently reported in clinical settings. However, whether ZIKV can be transmitted via aerosol routes remains unknown. In this study, we demonstrated that aerosolized ZIKV is fully infectious in vitro and in vivo. Remarkably, intratracheal (i.t.) inoculation with aerosolized ZIKV led to rapid viremia and viral secretion in saliva, as well as robust humoral and innate immune responses in guinea pigs. Transcriptome analysis further revealed that the expression of genes related to viral processes, biological regulation and the immune response was significantly changed. Together, our results confirm that aerosolized ZIKV can result in systemic infection and induce both innate and adaptive immune responses in guinea pigs, highlighting the possibility of ZIKV transmission via aerosols.

The infectivity and pathogenicity of hepatitis A virus live-attenuated vaccine strain H2 in type I interferon receptor-deficient mice.

Hepatitis A virus (HAV) live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans. Recently, type I interferon (IFN) receptor-deficient mice were shown to be susceptible to HAV infection. Herein, we sought to determine the infection and replication dynamics of the H2 in Ifnar-/- mice that lack type I IFN receptor. Following intravenous injection, the H2 failed to cause obvious clinical symptoms in Ifnar-/- mice, and no significant upregulation in serum alanine aminotransferase (ALT) levels was observed. Notably, the histopathological examination showed that there were significant focal infiltrations of lymphocytes and neutrophils in the portal area, but no focal necrosis was observed in liver tissues. Viral RNAs sustained in the liver, and the infectious virus could be recovered from the liver tissue until 42 days post-infection. More importantly, H2 infection induced obvious viremia and persistent viral shedding in feces. In addition, robust HAV-specific humoral immune responses were induced in Ifnar-/- mice. Overall, our study revealed the safety profile of H2 in Ifnar-/- mice, which not only helps understand the attenuation mechanism of H2, but also expands the application of the Ifnar-/- mouse model for HAV studies.

Long-term stability and protection efficacy of the RBD-targeting COVID-19 mRNA vaccine in nonhuman primates.

Messenger RNA (mRNA) vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic. Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use. Recently, we have developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor-binding domain (RBD) of SARS-CoV-2 (termed ARCoV), which confers complete protection in mouse model. Herein, we further characterized the protection efficacy of ARCoV in nonhuman primates and the long-term stability under normal refrigerator temperature. Intramuscular immunization of two doses of ARCoV elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques. More importantly, ARCoV vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2, and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of ARCoV. No evidence of antibody-dependent enhancement of infection was observed throughout the study. Finally, extensive stability assays showed that ARCoV can be stored at 2-8 °C for at least 6 months without decrease of immunogenicity. All these promising results strongly support the ongoing clinical trial.

Dietary exposure risk of bisphenol S in vegetables and fruits inHenan Province / 预防医学

Objective@#To monitor the content of bisphenol S ( BPS ) in vegetables and fruits in Henan Province and evaluate the dietary exposure risk of the population, so as to provide the basis for formulating relevant food safety standards.@*Methods@#From 2018 to 2019, 276 samples of vegetables and fruits produced and sold in Henan Province were collected. BPS was determined by isotope dilution ultra performance liquid chromatography triple quadrupole tandem mass spectrometry ( UPLC-MS/MS ) , and the dietary exposure was calculated according to the dietary structure and average body weight of local residents. The risk index of BPS was calculated according to the daily tolerable intake ( TDI ) of bisphenol A ( BPA ). @*Results@#The BPS contents in vegetables and fruits were 0.006-12.600 µg/kg and 0.006-9.380 µg/kg, the medians were 0.053 µg/kg and 0.023 µg/kg, the detection rates were 78.43% and 62.60%, respectively.The detection rate and content of BPS in vegetables were higher than those in fruits ( P<0.05 ). The maximum exposure of BPS from vegetables and fruits was 5.37×10-2 µg/ ( kgbw·d ), and the exposure risk index was 1.07 × 10-3, which was acceptable. @*Conclusions@#BPS was detected from vegetables and fruits in Henan Province. The detection rate and content of BPS in vegetables were higher than those in fruits. The health risk of BPS exposed by vegetables and fruits is small.

A Critical Time-Window for the Selective Induction of Hippocampal Memory Consolidation by a Brief Episode of Slow-Wave Sleep.

Although extensively studied, the exact role of sleep in learning and memory is still not very clear. Sleep deprivation has been most frequently used to explore the effects of sleep on learning and memory, but the results from such studies are inevitably complicated by concurrent stress and distress. Furthermore, it is not clear whether there is a strict time-window between sleep and memory consolidation. In the present study we were able to induce time-locked slow-wave sleep (SWS) in mice by optogenetically stimulating GABAergic neurons in the parafacial zone (PZ), providing a direct approach to analyze the influences of SWS on learning and memory with precise time-windows. We found that SWS induced by light for 30 min immediately or 15 min after the training phase of the object-in-place task significantly prolonged the memory from 30 min to 6 h. However, induction of SWS 30 min after the training phase did not improve memory, suggesting a critical time-window between the induction of a brief episode of SWS and learning for memory consolidation. Application of a gentle touch to the mice during light stimulation to prevent SWS induction also failed to improve memory, indicating the specific role of SWS, but not the activation of PZ GABAergic neurons itself, in memory consolidation. Similar influences of light-induced SWS on memory consolidation also occurred for Y-maze spatial memory and contextual fear memory, but not for cued fear memory. SWS induction immediately before the test phase had no effect on memory performance, indicating that SWS does not affect memory retrieval. Thus, by induction of a brief-episode SWS we have revealed a critical time window for the consolidation of hippocampus-dependent memory.

MicroRNA-96 Regulates Apoptosis by Targeting PDCD4 in Human Glioma Cells.

Glioblastoma multiforme, the most common and aggressive form of primary brain tumor, presents a dismal prognosis. MicroRNAs play a critical role in the initiation, progression, and metastasis of cancer; however, the potential biological role of miRNAs in glioblastoma multiforme remains largely unknown. In our study, we found that microRNA-96 is upregulated in glioma tissues than in normal human brains. Transfection of microRNA-96 mimics into glioma cells significantly decreases apoptosis by suppressing PDCD4, a well-known tumor suppressor that is involved in apoptosis. In contrast, knockdown of microRNA-96 enhanced apoptosis. In vivo, microRNA-96 overexpression inhibits the apoptosis and increases tumor growth. These data suggest that microRNA-96 is a potential molecular target for glioma treatment.

Cadmium(II)-Triazole Framework as a Luminescent Probe for Ca(2+) and Cyano Complexes.

A bidentate ligand, 1-{4-[4-(1H-1,2,4-triazol-1-yl)phenoxy]phenyl}-1H-1,2,4-triazole (TPPT), has been designed and synthesized. By using TPPT as a building block for self-assembly with Cd(NO3 )2 ⋅4 H2 O and CdCl2 ⋅10.5 H2 O, novel 1D double-chain {[Cd(TPPT)(NO3 )2 ]⋅3 H2 O}n (1) and 2D (4,4) layer [Cd(TPPT)Cl2 (H2 O)]n (2) have been constructed. When 1 was employed as a precursor and exposed to DMF or N,N'-dimethylacetamide (DMAC), the crystals of 1 dissolved and reassembled into two types of brown block-shaped crystals of 1D double chains: {[Cd(TPPT)2 (NO3 )2 ]⋅DMF}n (1 a) and {[Cd(TPPT)2 (NO3 )2 ]⋅DMAC}n (1 b). The anion-exchange reactions of complex 2 have also been investigated. After gently stirring crystals of 2 in CHCl3 /C2 H5 OH/H2 O containing NaBr, NaI⋅2 H2 O, or NaOAc⋅3 H2 O, the crystals retained their crystalline appearances. A remarkable single crystal to single crystal transformation was observed and 1D double chains of {[Cd(TPPT)Br2 ]⋅C2 H5 OH}n (2 a) and {[Cd(TPPT)2 I2 ]⋅CHCl3 }n (2 b), and 1D single chains of [Cd(TPPT)(H2 O)2 (CH3 COO)2 ]n (2 c), can be obtained. Luminescent properties indicate that 1 shows excellent selectivity for Ca(2+) and cyano complexes. To the best of our knowledge, this is the first example of a luminescent probe for Ca(2+) based on triazole derivatives.

Solvent-Induced Single Crystal-Single Crystal Transformation of an Interpenetrated Three-Dimensional Copper Triazole Catalytic Framework.

The 2-fold interpenetrated 3D framework 1 can be solvent-induced to noninterpenetrated framework 1' in a reversible single crystal-single crystal transformation fashion. In addition, 1' represents the first catalyst based on triazole to catalyze the aerobic homocoupling of various substituted arylboronic acids.

Effect of CXCR4 pretreated with ultrasound-exposed microbubbles on accelerating homing of bone marrow mesenchymal stem cells to ischemic myocardium in AMI rats.

OBJECTIVE: To investigate the role and potential mechanism of CXCR4 in promoting targeted homing of bone marrow mesenchymal stem cells (BMSCs) with ultrasound-exposed microbubbles (UM) pretreatment. METHODS: Third generation BMSCs were divided into four groups control group, ultrasound (US) group, UM group and ultrasound-exposed microbubbles plus catalase group. RT-PCR and western blot were performed to determine the levels of CXCR4 mRNA transcription and protein expression, respectively. Third generation BMSCs were labeled with Fluo-α/AM and divided into three groups: control group, US group and UM group, and fluorescence intensities in the cells were observed immediately, 5 min and 15 min after intervention under fluorescence microscope. The calcium iron levels in the cells were analyzed. BMSCs were divided into five group: group A without calcium in the medium, group B, group C, group D and group E containing calcium chloride with concentration of l mol, 2 mol, 4 mol, anti-calcium-sensing receptor antibody, respectively. RT-PCR and western blot were performed to determine the levels of CXCR4 mRNA transcription and proteins expression of the third generation BMSCs of each group, respectively. RESULTS: The levels of CXCR4 mRNA transcription and protein expression between US group and control group had no statistically significant difference (P > 0.05) shown by RT-PCR and western blot; the transcription level in the UM group was significantly higher than that in US group and control group (P < 0.05); and in the ultrasound-exposed microbubbles plus catalase group, the transcription level was much lower than that in UM group. Fluorescence intensify in the cells of US group had no significant difference compared with that in the cells of the control group (P > 0.05), which in the cells of UM group was significantly higher than that in the cells of both US group and control group (P < 0.05). Compared to group A, expressions of CXCR4 of group B to D were significantly increased in concentration-dependent manner showed by RT-PCR and western blot (P < 0.05). Compared to group C, expressions of CXCR4 of group E were significantly decreased (P < 0.05). CONCLUSIONS: UM can promote the influx of calcium in BMSCs and increase mRNA transcription and protein expression of CXCR4. The latter may partly be caused by influx of calcium.

Genetic structure in dwarf bamboo (Bashania fangiana) clonal populations with different genet ages.

Amplified fragment length polymorphism (AFLP) fingerprints were used to reveal genotypic diversity of dwarf bamboo (Bashania fangiana) clonal populations with two different genet ages (≤30 years versus >70 years) at Wolong National Natural Reserve, Sichuan province, China. We generated AFLP fingerprints for 96 leaf samples, collected at 30 m intervals in the two populations, using ten selective primer pairs. A total of 92 genotypes were identified from the both populations. The mean proportion of distinguishable genotypes (G/N) was 0.9583 (0.9375 to 0.9792) and Simpson's index of diversity (D) was 0.9982 (0.9973 to 0.9991). So, two B. fangiana populations were multiclonal and highly diverse. The largest single clone may occur over a distance of about 30 m. Our results demonstrated that the genotypic diversity and genet density of B. fangiana clonal population did not change significantly (47 versus 45) with genet aging and low partitioned genetic differentiation was between the two populations (Gst = 0.0571). The analysis of molecular variance consistently showed that a large proportion of the genetic variation (87.79%) existed among the individuals within populations, whereas only 12.21% were found among populations. In addition, the high level of genotypic diversity in the two populations implies that the further works were needed to investigate the reasons for the poor seed set in B. fangiana after flowering.