Flyback converter has advantages of simple circuit configuration and easy control. However, it suffers two problems. One is the active switch is hard switching. The other is a very high voltage spike ...when the active switch is turned off. In order to solve these problems, this paper presents a novel dc-to-dc converter that mainly consists of two interleaved flyback converters. Both active switches can achieve zero-voltage switching on without the use of any active clamp circuit or snubber circuit. In addition, the leakage flux energy can be delivered to the output by using two added diodes. It helps to reduce the voltage spikes on the active switches and improve circuit efficiency. The steady-state analyses at different operation modes and the mathematical equations for parameters design are provided. Finally, a 200-W prototype circuit for driving high-brightness light-emitting diodes (LEDs) is built and tested to verify the feasibility of the proposed circuit. The LEDs are dimmed from 100% to 10% full power. Satisfactory performances are obtained from the experimental results.
Alphaviruses are arboviruses transmitted by mosquitoes and are pathogenic to humans and livestock, causing a substantial public health burden. So far, several receptors have been identified for ...alphavirus entry; however, they cannot explain the broad host range and tissue tropism of certain alphaviruses, such as Getah virus (GETV), indicating the existence of additional receptors. Here we identify the evolutionarily conserved low-density lipoprotein receptor (LDLR) as a new cell entry factor for GETV, Semliki Forest virus (SFV), Ross River virus (RRV) and Bebaru virus (BEBV). Ectopic expression of LDLR facilitates cellular binding and internalization of GETV, which is mediated by the interaction between the E2-E1 spike of GETV and the ligand-binding domain (LBD) of LDLR. Antibodies against LBD block GETV infection in cultured cells. In addition, the GST-LBD fusion protein inhibits GETV infection both in vitro and in vivo. Notably, we identify the key amino acids in LDLR-LBD that played a crucial role in viral entry; specific mutations in the CR4 and CR5 domain of LDLR-LBD reduce viral entry to cells by more than 20-fold. These findings suggest that targeting the LDLR-LBD could be a potential strategy for the development of antivirals against multiple alphaviruses.
Abstract Various low-density lipoprotein receptors (LPRs) have been identified as entry factors for alphaviruses, and structures of the corresponding virion-receptor complexes have been determined. ...Here, we analyze the similarities and differences in the receptor binding modes of multiple alphaviruses to understand their ability to infect a wide range of hosts. We further discuss the challenges associated with the development of broad-spectrum treatment strategies against a diverse range of alphaviruses.
Rabies virus (RABV) causes fatal neurological encephalitis and results in approximately 6000 human death cases worldwide every year. The large (L) protein of RABV, possessing conserved domains, is ...considered as the target for detection. In this study, three monoclonal antibodies (mAbs), designated as 3F3, 3A6 and L-C, against L protein were generated by using the recombinant truncated L protein (aa 1431-1754) and the epitopes were also identified using a series of overlapping truncated polypeptides for testing the reactivity of mAbs with different RABV strains. The
EIFSIP
,
RALSK
and
VFNSL
were identified as the minimal linear epitopes recognized by mAbs 3F3, 3A6 and L-C, respectively. Amino acid alignment showed epitope
VFNSL
recognized by mAb L-C is completely conserved among RABV strains, indicating that mAb L-C could be used to detect all of the RABV strains. Epitope
EIFSIP
is highly conserved among RABV strains except for a P1484S substitution in a China I sub-lineage strain of Asian lineage, which eliminated the reactivity of the epitope with mAb 3F3. However, the epitope
RALSK
was only completely conserved in the Africa-2 and Indian lineages, and a single A1660T substitution, mainly appeared in strains of the China I belonging to Asian lineage and a Cosmopolitan lineage strain, still retained the reactivity of the epitope with mAb 3A6. While both A1660T and K1663R substitutions in a China I lineage strain, single K1663R/Q substitution in some China II strains of Asian lineage and some Arctic-like lineage strains and R1659Q mutation in a strain of Africa-3 lineage eliminated the reactivity of the epitope with mAb 3A6, suggesting mAb 3A6 could be used for differentiation of variable epitopes of some strains in different lineages. Thus, variability and conservation of the three epitopes of L protein showed the reactive difference of mAbs among RABV strains of different lineages. These results may facilitate future studies in development of detection methods for RABV infection, the structure and function of RABV L protein.
Canine parvovirus (CPV) type 2 emerged in 1978 in the USA and quickly spread among dog populations all over the world with high morbidity. Although CPV is a DNA virus, its genomic substitution rate ...is similar to some RNA viruses. Therefore, it is important to trace the evolution of CPV to monitor the appearance of mutations that might affect vaccine effectiveness.
Our analysis shows that the VP2 genes of CPV isolated from 1979 to 2016 are divided into six groups: GI, GII, GIII, GIV, GV, and GVI. Amino acid mutation analysis revealed several undiscovered important mutation sites: F267Y, Y324I, and T440A. Of note, the evolutionary rate of the CPV VP2 gene from Asia and Europe decreased. Codon usage analysis showed that the VP2 gene of CPV exhibits high bias with an ENC ranging from 34.93 to 36.7. Furthermore, we demonstrate that natural selection plays a major role compared to mutation pressure driving CPV evolution.
There are few studies on the codon usage of CPV. Here, we comprehensively studied the genetic evolution, codon usage pattern, and evolutionary characterization of the VP2 gene of CPV. The novel findings revealing the evolutionary process of CPV will greatly serve future CPV research.
Cerebral small vessel disease (CSVD), as the most common, chronic and progressive vascular disease on the brain, is a serious neurological disease, whose pathogenesis remains unclear. The disease is ...a leading cause of stroke and vascular cognitive impairment and dementia, and contributes to about 20% of strokes, including 25% of ischemic strokes and 45% of dementias. Undoubtedly, the high incidence and poor prognosis of CSVD have brought a heavy economic and medical burden to society. The present treatment of CSVD focuses on the management of vascular risk factors. Although vascular risk factors may be important causes or accelerators of CSVD and should always be treated in accordance with best clinical practice, controlling risk factors alone could not curb the progression of CSVD brain injury. Therefore, developing safer and more effective treatment strategies for CSVD is urgently needed. Recently, mesenchymal stem cells (MSCs) therapy has become an emerging therapeutic modality for the treatment of central nervous system disease, given their paracrine properties and immunoregulatory. Herein, we discussed the therapeutic potential of MSCs for CSVD, aiming to enable clinicians and researchers to understand of recent progress and future directions in the field.
•Cerebral small vessel disease contributes to aging, stroke, and dementia.•Currently, no treatment could be used to delay cerebral small vessel disease progressing.•Mesenchymal stem cells can protect neurons, cerebral microvessels and white matter.•Stem cell therapy may have a good therapeutic effect on cerebral small vessel disease.
We have demonstrated that nanoporous gold (AuNPore) is an efficient catalyst to promote the selective diboration of methylenecyclopropanes (MCPs) in a heterogeneous manner. Notably, the diboration ...takes place via a regioselective cleavage of the distal bond of the cyclopropane ring exclusively by AuNPore without using any additives. The experimental results and computational studies of the mechanism indicate that the present diboration proceeds through the formation of a relatively stable trimethylenemethane intermediate on the AuNPore surface with increased negative charges on trimethylene carbons, giving rise to the subsequent diboration selectively.
The torque teno sus virus (TTSuV) is an emerging virus threating the
species of unclear pathogenicity, although it was previously reported as a worsening factor of other porcine diseases, in ...particular, porcine circovirus associated disease (PCVAD). Here, a comprehensive codon usage analysis of the open reading frame 1 (ORF1), which encodes the viral capsid protein, was undertaken for the first time to reveal its evolutionary history. We revealed independent phylogenetic processes for the two genera during TTSuV evolution, which was confirmed by principal component analysis (PCA). A low codon usage bias was observed in different genera and different species, with Kappatorquevirus a (TTSuVk2a) displaying the highest, which was mainly driven by mutation pressure and natural selection, especially natural selection. Overall, ATs were more abundant than GCs, along with more A-ended synonymous codons in relative synonymous codon usage (RSCU) analysis. To further confirm the role of natural selection and TTSuV adaptation to the
species, codon adaptation index (CAI), relative codon deoptimization index (RCDI), and similarity index (SiD) analyses were performed, which showed different adaptations for different TTSuVs. Importantly, we identified a more dominant role of
in the evolution of
(TTSuV1), with the highest CAI values and lowest RCDI values compared to
. However, in TTSuVk2, the roles of
and
were the same, regarding codon usage, with similar CAI and RCDI values. Our study provides a new perspective of the evolution of TTSuV and valuable information to develop control measures against TTSuV.
Based to the first-principles calculations, we study the electronic properties of graphene/MoS2 heterostructure by modulating the vertical strains and applying external electric field. Graphene/MoS2 ...heterostructure is a van der Waals heterostructure (vdWH) with the interlayer spacing is 3.2 Å for the equilibrium state, and the contact property of the interface is n-type Schottky contact. The Schottky barrier height (SBH) changes with vertical strains which induces a change of charge transfer between graphene and MoS2 layer. In addition, with strain or without strain, the applied positive electric field can effectively promote the charge transfer from graphene to MoS2, while the negative electric field has the opposite effect. These findings support for the design of field effect transistors based on graphene vdWHs.
Display omitted .The interface contact properties of graphene/MoS2 heterostructure are modulated by strains and applied electric field, which contributes to the development of new nano electronic devices.
•The electronic properties of graphene/MoS2 can be modulated via strain and electric field.•Schottky barrier height is determined by charge transfer between graphene and MoS2 layers.•These findings support for the design of field-effect transistors based on graphene vdWHs.
Porcine circovirus 3 (PCV3) was found to be associated with reproductive disease in pigs, and since its first identification in the United States, it subsequently spread worldwide, especially in ...China, where it might pose a potential threat to the porcine industry. However, no exhaustive analysis was performed to understand its evolution in the prospect of codon usage pattern. Here, we performed a deep codon usage analysis of PCV3. PCV3 sequences were classified into two clades: PCV3a and PCV3b, confirmed by principal component analysis. Additionally, the degree of codon usage bias of PCV3 was slightly low as inferred from the analysis of the effective number of codons. The codon usage pattern was mainly affected by natural selection, but there was a co-effect of mutation pressure and dinucleotide frequency. Moreover, based on similarity index analysis, codon adaptation index analysis and relative codon deoptimization index analysis, we found that PCV3 might pose a potential risk to public health though with unknow pathogenicity. In conclusion, this work reinforces the systematic understanding of the evolution of PCV3, which was reflected by the codon usage patterns and fitness of this novel emergent virus.
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