Hair follicle-targeting drug delivery strategies for the management of hair follicle-associated disorders

The hair follicle is not only a critical penetration route in percutaneous absorption but also has been recognized to be a target for hair follicle-associated disorders,such as androgenetic alopecia(AGA)and acne vulgaris.Hair follicle-targeting drug delivery systems allow for controlled drug release and enhance therapeutic efficacywithminimal side effects,exerting a promising method for themanagement of hair follicle-associated dysfunctions.Therefore,they have obtained much attention in several fields of research in recent years.This review gives an overviewof potential follicle-targeting drug delivery formulations currently applied based on the particularities of the hair follicles,including a comprehensive assessment of their preclinical and clinical performance.

Influence of aging treatment on mechanical properties and wear resistance of medium manganese steel reinforced with Ti(C,N) particles

In this study,the hot rolled medium manganese steel containing titanium was solution treated at 1,000°C and followed by aging treatment at 500,550,and 600°C.The influence of aging treatment on mechanical properties and wear resistance of medium manganese steel reinforced with Ti(C,N)particles was investigated.It was found that the matrix of medium manganese steel was austenite.The austenite grain size was refined,and Ti(C,N)particles were precipitated after aging treatment.Compared to that of the as-hot rolled sample,the initial hardness of 500°C aged sample increased by 9.5%to 312.86 HV,whose impact energy was more than doubled to 148.5 J.As the aging temperature raised to 600°C,the initial hardness changed slightly.However,the impact energy dropped significantly to 8 J due to the aggregation of Mn at the grain boundaries.In addition,the main wear mechanisms of the samples were fatigue wear and abrasive wear.It was worth noting that 500°C aged sample exhibited the best wear resistance under a 300 N applied load,whose wear loss was just half of the as-hot rolled sample.The relationship between wear loss and mechanical properties indicated that the wear resistance of medium manganese steel was independent of the initial hardness.The large difference in the wear resistance was predominately due to the outstanding work hardening ability of 500°C aged sample,whose strengthening mechanisms were contributed from transformation induced plasticity(TRIP)effect,dislocation strengthening,twinning induced plasticity(TWIP)effect,and precipitation strengthening.

A Virulent PEDV Strain FJzz1 with Genomic Mutations and Deletions at the High Passage Level Was Attenuated in Piglets via Serial Passage In Vitro

Highly virulent porcine epidemic diarrhea virus(PEDV)strains re-emerged and circulated in China at the end of 2010,causing significant economic losses in the pork industry worldwide.To understand the genetic dynamics of PEDV during its passage in vitro,the PEDV G2 strain FJzzl was serially propagated in Vero cells for up to 200 passages.The susceptibility and adaptability of the FJzzl strain increased gradually as it was serially passaged in vitro.Sequence analysis revealed that amino acid(aa)changes were mainly concentrated in the S glycoprotein,which accounted for 72.22%-85.71%of all aa changes.A continuous aa deletion(^(55)I^(56)G^(57)E→^(55)K^(56)Δ^(57)Δ)occurred in the N-terminal domain of S1(Sl-NTD).To examine how the aa changes affected its virulence,FJzzl-F20 and FJzzl-F200 were selected to simultaneously evaluate their pathogenicity in suckling piglets.All the piglets in the FJzzl-F20-infected group showed typical diarrhea at 24 h postinfection,and the piglets died successively by 48 h postinfection.However,the clinical signs of the piglets in the FJzzl-F200-infected group were significantly weaker,and no deaths occurred.The FJzzl-F200-infected group also showed a lower level of fecal viral shedding and lower viral loads in the intestinal tissues,and no obvious histopathological lesions.TypeⅠandⅢinterferon were induced in the FJzzl-F200 infection group,together with pro-inflammatory cytokines,such as TNF-α,IL-1βand IL-8.These results indicate that the identified genetic changes may contribute to the attenuation of FJzzl strain,and the attenuated FJzzl-F200 may have the potential for developing PEDV live-attenuated vaccines.

Effects of strain rates on dynamic deformation behavior of Cu-20Ag alloy

Copper alloy is widely used in high-speed railway,aerospace and other fields due to its excellent electrical conductivity and mechanical properties.High speed deformation and dynamic loading under impact load is a complex service condition,which widely exists in the field of national defense,military and industrial application.Therefore,the dynamic deformation behavior of the Cu-20Ag alloy was investigated by Split Hopkinson Pressure Bar(SHPB)with the strain rates of 1000-25000 s^(-1),high-speed hydraulic servo material testing machine with the strain rates of 1-500 s^(-1).The effect of strain rate on flow stress and adiabatic shear sensitivity was analyzed.The results show that the increase of strain rate will increase the flow stress and critical strain,that is to say,the increase of strain rate will reduce the adiabatic shear sensitivity of the Cu-20Ag alloy.The Cu-Ag interface has obvious orientation relationship with;(111)_(Cu)//(111)_(Ag):(^(-)111)_(Cu)//(^(-)111)_(Ag):(^(-)200)_(Cu)//(^(-)200)_(Ag) and [0^(-)11]_(Cu)//[0^(-)11]_(Ag) with the increase of strain rate.The increase of strain rate promotes the precipitation of Ag and increases the number of interfaces in the microstructure,which hinders the movement of dislocations and improves the stress and yield strength of the Cu-20Ag alloy.The concentration and distribution density of dislocations and the precipitation of Ag were the main reasons improve the flow stress and yield strength of the Cu-20Ag alloy.

Coordinated grain boundary deformation governed nanograin annihilation in shear cycling

Grain growth and shrinkage are essential to the thermal and mechanical stability of nanocrystalline metals,which are assumed to be governed by the coordinated deformation between neighboring grain boundaries(GBs)in the nanosized grains.However,the dynamics of such coordination has rarely been reported,especially in experiments.In this work,we systematically investigate the atomistic mechanism of coordinated GB deformation during grain shrinkage in an Au nanocrystal film through combined stateof-the-art in situ shear testing and atomistic simulations.We demonstrate that an embedded nanograin experiences shrinkage and eventually annihilation during a typical shear loading cycle.The continuous grain shrinkage is accommodated by the coordinated evolution of the surrounding GB network via dislocation-mediated migration,while the final grain annihilation proceeds through the sequential dislocation-annihilation-induced grain rotation and merging of opposite GBs.Both experiments and simulations show that stress distribution and GB structure play important roles in the coordinated deformation of different GBs and control the grain shrinkage/annihilation under shear loading.Our findings establish a mechanistic relation between coordinated GB deformation and grain shrinkage,which reveals a general deformation phenomenon in nanocrystalline metals and enriches our understanding on the atomistic origin of structural stability in nanocrystalline metals under mechanical loading.

Cu-10Sn-4Ni-3Pb Alloy Prepared by Crystallization Under Pressure: An Experimental Study

The wear-resistant tin bronze （Cu-10Sn-4Ni-3Pb） with tin content above 8 wt.% prepared by traditional melting and casting process usually defects such as low density, poor properties and segregations. The crystallization under pressure processing of Cu-10Sn-4Ni-3Pb alloy was investigated. The microstructures were observed and analyzed and compared with that by traditional melting and casting process. The results show that the dendrite has obviously disappeared and the dendritic segregation alleviated by using the crystallization under 680 MPa pressure process, in comparison with the remarkably dendrite microstructure and severe as-cast defects of alloy prepared by traditional melting and casting technology. Based on the experimental study, the properties and microstructures of Cu-10Sn-4Ni-3Pb tin bronze prepared by crystallization under pressure have been improved significantly.

The Novel PRRSV Strain HBap4-2018 with a Unique Recombinant Pattern Is Highly Pathogenic to Piglets

Currently, various porcine reproductive and respiratory syndrome virus(PRRSV) variants emerged worldwide with different genetic characteristics and pathogenicity, increasing the difficulty of PRRS control. In this study, a PRRSV strain named HBap4-2018 was isolated from swine herds suffering severe respiratory disease with high morbidity in Hebei Province of China in 2018. The genome of HBap4-2018 is 15,003 nucleotides in length, and compared with NADC30-like PRRSV, nsp2 of HBap4-2018 has an additional continuous deletion of five amino acids. Phylogenetic analysis based on complete genome and ORF5 showed that HBap4-2018 belonged to lineage 8 of PRRSV-2, which was characterized by highly variable genome. However, HBap4-2018 was classified into lineage 1 based on phylogenetic analysis of nsp2,sharing higher amino acid homology(85.3%–85.5%) with NADC30-like PRRSV. Further analysis suggested that HBap4-2018 was a novel natural recombinant PRRSV with three recombinant fragments in the genome, of which highly pathogenic PRRSV(HP-PRRSV) served as the major parental strains, while NADC30-like PRRSV served as the minor parental strains. Five recombination break points were identified in nsp2, nsp3, nsp5, nsp9 and ORF6, respectively,presenting a novel recombinant pattern in the genome. Piglets inoculated with HBap4-2018 presented typical clinical signs with a mortality rate of 60%. High levels of viremia and obvious macroscopic and histopathological lesions in the lungs were observed, revealing the high pathogenicity of HBap4-2018 in piglets.

Arc Erosion Behavior of Cu–0.23Be–0.84Co Alloy after Heat Treatment: An Experimental Study

The arc erosion behavior of Cu-0.23Be-0.84Co alloy after heat treatment was investigated experimentally by a JF04C electric contact test system. The arc duration, arc energy, contact resistance and contact pressure of Cu-0.23Be- 0.84Co alloy after solution treatment and aging treatment were analyzed. The arc erosion morphologies were contrastively observed by a three-dimensional measuring system and scanning electron microscopy. For the Cu-0.23Be-0.84Co alloy in solution state and aging state, the maximum values of arc duration are 90 and 110 ms, and the arc energies are 15,000 and 18,000 mJ, respectively. The maximum value of the contact resistance of Cu-0.23Be-0.84Co alloy in different states is about 33 mΩ The contact pressure of Cu-0.23Be-0.84Co alloy in solution state generally changes between 50 and 60 cN during whole make-and-break contacts, while in aging state, it has a larger fluctuation range. Moreover, the quality of moving contact （anode） decreases, while static contact （cathode） increases. The materials transfer from anode to cathode during make-and-break contacts. The total mass losses of Cu-0.23Be-0.84Co alloy in solution state and aging state are 3 and 1.2 mg, respectively. In addition, a number of discrete corrosion pits, molten droplet, porosity and cavity distribute on the surface of moving contact and static contact. The arc erosion model of Cu-0.23Be-0.84Co alloy in make-and-break contact was built. The arc erosion resistance of Cu-0.23Be-0.84Co alloy after heat treatment is closely related to the microstructure and the properties of contact materials. This experimental study is important to evaluate the anode or cathode electrocorrosion fatigue life.

Genetic characterization and pathogenicity of a reassortant Eurasian avian-like H1N1 swine influenza virus containing an internal gene cassette from 2009 pandemic H1N1 virus

Dear editor,Swine influenza virus(SIV)is a member of the Orthomyxoviridae family,influenza A virus genus,which can cause the swine influenza—an acute and highly contagious respiratory disease in pigs(Brown,2000;Kothalawala et al.,2006).The SIV was first observed in 1918 in the United States and the progenitor of the SIV was the H1N1 influenza virus which caused the Spanish influenza pandemic of 1918(Shope,1931).