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The porcine reproductive and respiratory syndrome virus (PRRSV) belongs to the Arteriviridae family and is a single-stranded, positively stranded RNA virus. The currently available PRRSV vaccines are mainly inactivated and attenuated vaccines, yet none of the commercial vaccines can provide comprehensive, long-lasting, and effective protection against PRRSV. SR717 is a pyridazine-3-carboxamide compound, which is commonly used as a non-nucleoside STING agonist with antitumor and antiviral activities. Nevertheless, there is no evidence that SR717 has any antiviral effects against PRRSV. In this study, a dose-dependent inhibitory effect of SR717 was observed against numerous strains of PRRSV using qRT-PCR, IFA, and WB methods. Furthermore, SR717 was found to stimulate the production of anti-viral molecules and trigger the activation of the signaling cascade known as the stimulator of interferon genes (STING) pathway, which contributed to hindering the reproduction of viruses by a certain margin. Collectively, these results indicate that SR717 is capable of inhibiting PRRSV infection in vitro and may have potential as an antiviral drug against PRRSV. [ABSTRACT FROM AUTHOR]

Aim: Type II diabetes (T2D) stems from insulin resistance, with β-cell dysfunction as a hallmark in its progression. Studies reveal that β cells undergo apoptosis or dedifferentiation during T2D development. The transcription factor PAX4 is vital for β differentiation and survival, thus may be a potential enhancer of β-cell function in T2D islets. Materials & methods: Human PAX4 cDNA was delivered into T2D human islets with an adenoviral vector, and its effects on β cells were examined. Results: PAX4 gene delivery significantly improved β-cell survival, and increased β-cell composition in the T2D human islets. Basal insulin and glucose-stimulated insulin secretion in PAX4-expressing islets were substantially higher than untreated or control-treated T2D human islets. Conclusion: Introduced PAX4 expression in T2D human islets improves β-cell function, thus could provide therapeutic benefits for T2D treatment. Type II diabetes (T2D) results from insulin resistance, with β-cell dysfunction playing a pivotal role in its progression. Deficits in β-cell mass and function have been attributed primarily to β-cell death through apoptosis; however, recent studies suggest β-cell failure can also arise from β-cell dedifferentiation – that is, β cells undergo a loss of mature identity, adopting either progenitor-like or glucagon-producing α cell states during T2D development. Therefore, a strategy preventing β-cell dedifferentiation while promoting its survival is beneficial for T2D treatment. In this study, we explored whether PAX4, a critical transcription factor for β differentiation and survival, could alleviate β-cell dysfunction in human islets derived from T2D patients. To accomplish that, human PAX4 cDNA was delivered into human islets isolated from T2D donors by an adenoviral vector-based vector, Ad5.Pax4 and its effects on β-cell function were evaluated. The results showed PAX4 expression significantly improved β-cell survival and increased β-cell composition in the T2D islets. Notably, PAX4-treated T2D islets exhibited significantly higher basal insulin secretion and glucose-stimulated insulin secretion than control-treated islets. The data demonstrate that PAX4 gene delivery into T2D human islets enhances β-cell mass and function, and thus may offer therapeutic benefits in the treatment of T2D. Article highlights Type II diabetes (T2D) arises from insulin resistance, with β-cell dysfunction as a hallmark in its progression, underscoring the need for therapies that enhance β-cell function. The transcription factor PAX4 plays critical roles in β differentiation and survival, making it a potential enhancer of β-cell function in T2D human islets. PAX4 gene delivery mediated by an adenoviral vector, Ad5.Pax4, increases the composition of β cells, enhances their survival, and improves their function in T2D human islets. PAX4 gene delivery may offer therapeutic benefits for T2D treatment by restoring β-cell function through Pax4's effects on β differentiation and survival, thereby improving glucose homeostasis and overall disease management. [ABSTRACT FROM AUTHOR]

Polymers with high thermal conductivity (TC) and dielectric constant (ε) but low dielectric loss show enormously potential applications in electrical power systems. To enhance the ε and TC while significantly suppressing the loss of β‐silicon carbide whisker (β‐SiCw)/polyvinylidene fluoride (PVDF), in this study, SiO2 shells with different morphologies were constructed on the superficies of β‐SiCw via a facile oxidation method in air atmosphere. The SiO2 shell' morphology on the TC and dielectric performances of the β‐SiCw@SiO2/PVDF are systematically explored as a function of the frequency and filler loading. The β‐SiCw@SiO2/PVDF demonstrate astonishingly restricted loss and meliorative TC when compared to the β‐SiCw/PVDF because the SiO2 shell not only suppresses the β‐SiCw from direct contact with one another and impedes the long‐distance charges migration thereby resulting in rather low loss and leakage conductivity, but also restrains the thermal interfacial resistance via increased interfacial compatibility and interactions. The concurrent enhancement effect in the ε and TC but low loss of the composites is more evident in the crystalline SiO2 interlayer with a high TC compared with amorphous one. These results provide insight into the exploration of composite nanodielectrics with large TC and ε but low loss for applications in electrical power systems. Highlights: Core@shell structured β‐SiCw@SiO2/PVDF were obtained by a facile oxidation.The great reduction in both loss and conductivity is attributed to the SiO2 shell.Crystalline SiO2 shell can improve the composites' thermal conductivity.The SiO2 shell prevents long‐range carrier migration. [ABSTRACT FROM AUTHOR]

To efficaciously decrease dielectric loss while still synchronously harvesting a high dielectric constant (ε′) and breakdown strength (Eb), as well as good mechanical properties in silicon (Si)/poly(vinylidene fluoride) (PVDF), in this work, the core@shell structured Si@silicon dioxide (SiO2) particles were first prepared via a high temperature oxidation, and subsequently incorporated into the PVDF to generate morphology‐dependent composites with a high‐ε′ and Eb but low loss. The SiO2 shell effects on the morphology, dielectric, and mechanical properties of PVDF composites were explored. In comparison to pristine Si/PVDF, the Si@SiO2/PVDF presents significantly suppressed loss and boosted Eb because the SiO2 interlayer not only efficiently blocks the connection between the raw Si and greatly impedes the long‐range charges migration even at high filler loadings, but also obviously improves the compatibility between Si and PVDF at the interfaces which promotes fillers' uniform dispersion in host matrix, thus leading to enhanced dielectric and mechanical properties. The fitting result by the Havriliak–Negami equation theoretically elucidates the SiO2 interlayer's suppression effect on charge migration behavior in the composites. More importantly, dielectric properties can be efficiently turned via tailoring the SiO2 shell thickness. The Si@SiO2/PVDF with simultaneously enhanced dielectric and mechanical performances shows promising uses in the electrical and microelectronics industries. [ABSTRACT FROM AUTHOR]

The problems of underdeveloped pores and high electrochemical impedance of oxygen reduction reaction (ORR) catalysts need to be urgently addressed. Heteroatoms F and N are doped on precursor Fe‐zeolitic imidazolate framework (ZIF)‐8 to increase the activity of Fe‐ZIF‐8‐derived porous carbon materials and a noble metal‐free high‐activity ORR catalyst F–N/FeNC with 3D interconnected porous structure and high conductivity is successfully prepared. Experiments show that the synergistic effect of CF ionic bonds, pyridinic‐N, pyrrolic‐N, graphitic‐N, FeNx sites, and CF semi‐ionic bonds in F–N/FeNC can improve the ORR activity of the F–N/FeNC. The developed F–N/FeNC is advantageous with excellent specific surface area, ultra‐high electrical conductivity, and extremely high ORR mass transfer efficiency. As such, the F–N/FeNC has a high onset potential of 0.95 V (vs RHE) and a half‐wave potential of 0.84 V (vs RHE), implying excellent ORR performance even better than commercially available Pt/C catalyst. In addition, the carefully prepared F–N/FeNC demonstrated higher long‐term durability and excellent resistance to methanol influence compared with commercially available Pt/C catalyst. The developed strategy provides new insights into heteroatom‐doped metal–organic frameworks as a precursor of ORR catalysts. [ABSTRACT FROM AUTHOR]

In order to synchronously improve dielectric permittivity (ε′), breakdown strength (Eb), and thermal conductivity (TC) while inhibiting dissipation factor (tan δ) of raw Zn (Zinc)/PVDF (poly[vinylidene fluoride]) composites, two kinds of core‐shell structured particles of Zn@ZnO (zinc oxide) and Zn@ZnO@PS (polystyrene) were synthesized by high‐temperature oxidation followed by suspension polymerization, then they were composited with PVDF to elaborately generate morphology‐controllable high‐ε′ but low loss, and high TC composites. The results confirm that both the Zn@ZnO/PVDF and Zn@ZnO@PS/PVDF composites show markedly improved ε′, suppressed tan δ and conductivity over the original Zn/PVDF because of the induced multiple polarizations in the Zn@ZnO and Zn@ZnO@PS configurations and the barrier effect of constructed shells on direct contact of Zn particles. The second organic PS shell inhibits the loss and conductivity due to its high‐electrical resistivity, and further boosts the Eb and TC of the composites owing to enhanced interfacial compatibility between the Zn@ZnO and PVDF, which lessens the local electric field distortion and concentration, and therefore, promotes phonon transport across the interfaces through suppressing the thermal interfacial resistance. The prepared Zn@ZnO@PS/PVDF with a high Eb and ε′ but low tan δ, as well as enhanced TC, exhibit appealing potential applications in microelectronic devices and power equipment. [ABSTRACT FROM AUTHOR]

Polymer dielectrics have received increasing attention owing to their wide applications in electrical, microelectronic and energy storage fields. However, it remains a challenging to prepare polymer dielectrics with a high dielectric constant (ε) but low dissipation factor (tanδ). In this work, conductive molybdenum (Mo) particles were encapsulated by a thin layer of semi-conductive molybdenum trioxide (MoO3) with a wide bandgap of 3.28 eV via a facile thermal calcination way under air, and the gained core–shell structured Mo@MoO3 particles were composited with poly(vinylidene fluoride) (PVDF) to generate morphology-controllable high-ε but low loss composites. The large ε can be realized in the PVDF composites with the Mo@MoO3, and both the electric conductivity and tanδ of the composites are significantly restrained to rather low levels even at high filler loadings, and apparently decrease with increasing the MoO3' shell thickness. The significantly ameliorated dielectric performances can be ascribed to the presence of MoO3 interlayer preventing the Mo particles from direct contact with each other and simultaneously hindering the long-range electron migration. The developed Mo@MoO3/PVDF composites with a high ε but low loss are great potential applications for electrical industries and microelectronic industries. [ABSTRACT FROM AUTHOR]

Exploring polymer composites with a high dielectric constant (ε′) and breakdown strength (Eb), low dissipation factor (tanδ), as well as a high thermal conductivity (TC) is of crucially important thanks to their potential applications in modern electronics. Herein, in this paper, two kinds of core–shell-structured Si particles, i.e., Si@SiO2, Si@SiO2@PS, were prepared by high temperature oxidation and polystyrene (PS) coating and incorporated into PVDF (poly(vinylidene fluoride)). The results indicate that both the fillers' kinds and loading have obvious influences on dielectric and thermal properties of the composites. The SiO2 interlayer between the Si and PVDF matrix remarkably suppresses the loss and reduces leakage conductivity, whereas encapsulation of Si@SiO2 with a PS shell further inhibits the loss and conductivity, and the organic PS interlayer enhances the interfacial compatibility and promotes the fillers' homogeneous dispersion in PVDF, therefore improving the Eb of the composites. More importantly, the PVDF composites with 50 wt.% of Si@SiO2@PS show good comprehensive performances: ε′ of 66.6 but tanδ of 0.04 at 100 Hz, Eb of 2.48 kV/mm as well as a high TC of 1.0 W/m K. The prepared Si@SiO2@PS/PVDF composites show promising potential applications in microelectronics and electrical industries. [ABSTRACT FROM AUTHOR]

Abstract Despite the many potential advantages of Ad vectors for vaccine application, the full utility of current Ad vaccines may be limited by the host anti-vector immune response. Direct incorporation of antigens into the adenovirus capsid offers a new and exciting approach for vaccination strategies; this strategy exploits the inherent antigenicity of the Ad vector. Critical to exploiting Ad in this new context is the placement of antigenic epitopes within the major Ad capsid protein, hexon. In our current study we illustrate that we have the capability to place a range of antigenic epitopes within Ad5 capsid protein hexon hypervariable regions (HVRs) 2 or 5, thus producing viable Ad virions. Our data define the maximal incorporation size at HVR2 or HVR5 as it relates to identical antigenic epitopes. In addition, this data suggests that Ad5 HVR5 is more permissive to a range of insertions. Most importantly, repeated administration of our hexon-modified viruses resulted in a secondary anti-antigen response, whereas minimal secondary effect was present after administration of Ad5 control. Our study describes antigen placement and optimization within the context of the capsid incorporation approach of Ad vaccine employment, thereby broadening this new methodology.

Abstract Background Human adenovirus serotype 5 (Ad5) has been widely explored as a gene delivery vector for a variety of diseases. Many target cells, however, express low levels of Ad5 native receptor, the Coxsackie-Adenovirus Receptor (CAR), and thus are resistant to Ad5 infection. The Protein Transduction Domain of the HIV Tat protein, namely PTDtat, has been shown to mediate protein transduction in a wide range of cells. We hypothesize that re-targeting Ad5 vector via the PTDtat motif would improve the efficacy of Ad5-mediated gene delivery. Results In this study, we genetically incorporated the PTDtat motif into the knob domain of Ad5 fiber, and rescued the resultant viral vector, Ad5.PTDtat. Our data showed the modification did not interfere with Ad5 binding to its native receptor CAR, suggesting Ad5 infection via the CAR pathway is retained. In addition, we found that Ad5.PTDtat exhibited enhanced gene transfer efficacy in all of the cell lines that we have tested, which included both low-CAR and high-CAR decorated cells. Competitive inhibition assays suggested the enhanced infectivity of Ad5.PTDtat was mediated by binding of the positively charged PTDtat peptide to the negatively charged epitopes on the cells' surface. Furthermore, we investigated in vivo gene delivery efficacy of Ad5.PTDtat using subcutaneous tumor models established with U118MG glioma cells, and found that Ad5.PTDtat exhibited enhanced gene transfer efficacy compared to unmodified Ad5 vector as analyzed by a non-invasive fluorescence imaging technique. Conclusion Genetic incorporation of the PTDtat motif into Ad5 fiber allowed Ad5 vectors to infect cells via an alternative PTDtat targeting motif while retaining the native CAR-mediated infection pathway. The enhanced infectivity was demonstrated in both cultured cells and in in vivo tumor models. Taken together, our study identifies a novel tropism expanded Ad5 vector that may be useful for clinical gene therapy applications.