A biomimetic basementmembrane consisted of hybrid aligned nanofibers andmicrofibers with immobilized collagen IV and laminin for rapid endothelialization

Rapid formation of a continuous endothelial cell(EC)monolayer with healthy endothelium function on the luminal surface of vascular implants is imperative to improve the longtime patency of small-diameter vascular implants.In the present study,we combined the contact guidance effects of aligned nanofibers,which enhance EC adhesion and proliferation because of its similar fiber scale with native vascular basement membranes,and aligned microfibers,which could induce EC elongation effectively and allow ECs infiltration.It was followed by successive immobilization of collagen IV and laminin to fabricate a biomimetic basement membrane(BBM)with structural and compositional biomimicry.The hemolysis assay and platelet adhesion results showed that the BBM exhibited excellent hemocompatibility.Meanwhile,the adhered human umbilical vein endothelial cells(HUVECs)onto theBBMaligned along the orientation of the microfibers with an elongated morphology,and the data demonstrated that the BBM showed favorable effects on EC attachment,proliferation,and viability.The oriented EC monolayer formed on the BBM exhibited improved antithrombotic capability as indicated by higher production of nitric oxide and prostacyclin(PGI2).Furthermore,fluorescence images indicated that HUVECs could infiltrate into the BBM,implying theBBM’s ability to enhance transmural endothelialization.Hence,theBBMpossessed the properties to regulate ECbehaviors and allow transmural ingrowth,demonstrating the potential to be applied as the luminal surface of small-diameter vascular implants for rapid endothelialization.

Cannabidiol-Mediated Sequestration of Alzheimer’s Amyloid-β Peptides in ADDL Oligomers

Cannabidiol (CBD), one of the most studied phytocannabinoids, is non-psychotropic and can induce protective effects on the central nervous system against acute and chronic brain injury. Interestingly, CBD inhibits processes relating to amyloid beta (Aβ)-induced neurotoxicity in mouse models of Alzheimer’s disease, though the detailed molecular mechanism underlying the CBD neurotoxicity modulation is not fully understood. In this study, using atomic force microscopy, we find that CBD promotes the aggregation of Aβ peptides, enhancing the formation of Aβ oligomers, also known as Aβ-derived diffusible ligands (ADDLs). The CBD-mediated sequestration of Aβ monomers in soluble ADDLs could reduce neurotoxicity. This study highlights a possible role of CBD in modulating the formation of ADDL aggregates and provides insight into potentially neuroprotective properties of CBD in Alzheimer’s disease.

化学物理联合微孔发泡成型制备聚己内酯多孔材料

将超临界气体发泡技术与化学发泡技术联合用于制备多孔材料。采用碳酸氢钠作为化学发泡剂,将聚己内酯与碳酸氢钠挤出共混之后,使用传统注射成型和微注射成型,进行了发泡实验对比。结果表明,物理化学联合发泡用于制备多孔材料具有可行性,化学发泡剂的加入不仅改善了整体发泡效果,还能够作为气泡成核剂促进物理发泡的质量。对于所得结构在一定程度上表现的泡孔相互连通性进行了讨论,同时对泡孔壁面上出现的"网"状结构进行了分析。气泡在成核生长过程中,对于泡孔壁产生多方向拉伸的作用,相邻气泡共同作用于公共壁面,最终导致壁面部分形成"网"状结构。

Fabrication of shish-kebab-structured carbon nanotube/poly(ε-caprolactone) composite nanofibers for potential tissue engineering applications

The electrospinning process was applied to fabricate the nanofibers of biodegradable poly(ε-caprolactone)(PCL) in which different contents of multiwalled carbon nanotubes(MWCNTs) were embedded. Afterward,the electrospun nanofibers were successfully decorated with shish-kebab structure via a self-induced crystallization technique. The topographical features and the mechanical properties of the composite scaffolds were characterized,and the biocompatibility of the material was assessed by using human osteogenic sarcoma osteoblasts(MG-63 cells). The carbon nanotube(CNT) concentration is found to affect the fiber diameter and mechanical properties of electrospun nanofibers and the periodic distance of the shish-kebab architecture. Cellular attachment and proliferation assays reveal that 0.5 wt% CNT-embedded PCL scaffold shows enhanced biocompatibility with MG-63 cells than their counterparts made of neat PCL, and the collagen-like nanotopology provided by the shish-kebab structure further facilitates the cell adhesion and proliferation. The superior interactions between cells and scaffolds demonstrate that the shish-kebab-structured CNTs/PCL nanofibers may be promising candidate for tissue engineering scaffold application.

Microcellular injection molding process for producing lightweight thermoplastic polyurethane with customizable properties

A three-stage molding process involving microcellular injection molding with core retraction and an ＂out-of-mold＂ expansion was developed to manufacture thermoplastic polyurethane into lightweight foams of varying local densities, microstructures, and mechanical properties in the same microcellular injection molded part. Two stages of cavity expansion through sequential core retractions and a third expansion in a separate mold at an elevated temperature were carried out. The densities varied from 0.25 to 0.42 g/cm3 （77% to 62% weight reduction）. The mechanical properties varied as well Cyclic com- pressive strengths and hysteresis loss ratios, together with the microstructures, were characterized and reported.

Micromolded honeycomb scaffold design to support the generation of a bilayered RPE and photoreceptor cell construct

Age-related macular degeneration(AMD)causes blindness due to loss of retinal pigment epithelium(RPE)and photoreceptors(PRs),which comprise the two outermost layers of the retina.Given the small size of the macula and the importance of direct contact between RPE and PRs,the use of scaffolds for targeted reconstruction of the outer retina in later stage AMD and other macular dystrophies is particularly attractive.We developed microfabricated,honeycomb-patterned,biodegradable poly(glycerol sebacate)(PGS)scaffolds to deliver organized,adjacent layers of RPE and PRs to the subretinal space.Furthermore,an optimized process was developed to photocure PGS,shortening scaffold production time from days to minutes.The resulting scaffolds robustly supported the seeding of human pluripotent stem cell-derived RPE and PRs,either separately or as a dual celllayered construct.These advanced,economical,and versatile scaffolds can accelerate retinal cell transplantation efforts and benefit patients with AMD and other retinal degenerative diseases.

Targeted PERK inhibition with biomimetic nanoclusters confers preventative and interventional benefits to elastase-induced abdominal aortic aneurysms

Abdominal aortic aneurysm(AAA)is a progressive aortic dilatation,causing~80%mortality upon rupture.Currently,there is no approved drug therapy for AAA.Surgical repairs are invasive and risky and thus not recommended to patients with small AAAs which,however,account for~90%of the newly diagnosed cases.It is therefore a compelling unmet clinical need to discover effective non-invasive strategies to prevent or slow down AAA progression.We contend that the first AAA drug therapy will only arise through discoveries of both effective drug targets and innovative delivery methods.There is substantial evidence that degenerative smooth muscle cells(SMCs)orchestrate AAA pathogenesis and progression.In this study,we made an exciting finding that PERK,the endoplasmic reticulum(ER)stress Protein Kinase R-like ER Kinase,is a potent driver of SMC degeneration and hence a potential therapeutic target.Indeed,local knockdown of PERK in elastase-challenged aorta significantly attenuated AAA lesions in vivo.In parallel,we also conceived a biomimetic nanocluster(NC)design uniquely tailored to AAA-targeting drug delivery.This NC demonstrated excellent AAA homing via a platelet-derived biomembrane coating;and when loaded with a selective PERK inhibitor(PERKi,GSK2656157),the NC therapy conferred remarkable benefits in both preventing aneurysm development and halting the progression of pre-existing aneurysmal lesions in two distinct rodent models of AAA.In summary,our current study not only establishes a new intervention target for mitigating SMC degeneration and aneurysmal pathogenesis,but also provides a powerful tool to facilitate the development of effective drug therapy of AAA.

Functions and mechanisms of plant histone deacetylases

Lysine acetylation, one of the major types of post-translational modifications, plays critical roles in regulating gene expression and protein function. Histone deacetylases(HDACs) are responsible for removing acetyl groups from lysines of both histone and non-histone proteins. While tremendous progress has been made in understanding the function and mechanism of HDACs in animals in the past two decades, nearly half of the HDAC studies in plants were reported within the past five years. In this review,we summarize the major findings on plant HDACs, with a focus on the model plant Arabidopsis thaliana, and highlight the components, regulatory mechanisms, and biological functions of HDAC complexes.

Fabrication of scaffolds in tissue engineering： A review

Tissue engineering （TE） is an integrated discipline that involves engineering and natural science in the development of biological materials to replace, repair, and improve the function of diseased or missing tissues. Traditional medical and surgical treatments have been reported to have side effects on patients caused by organ necrosis and tissue loss. However, engineered tissues and organs provide a new way to cure specific diseases. Scaffold fabrication is an important step in the TE process. This paper summarizes and reviews the widely used scaffold fabrication methods, including conventional methods, electrospinning, three-dimensional printing, and a combination of molding techniques. Furthermore, the differences among the properties of tissues, such as pore size and distribution, porosity, structure, and mechanical properties, are elucidated and critically reviewed. Some studies that combine two or more methods are also reviewed. Finally, this paper provides some guidance and suggestions for the future of scaffold fabrication.

A Malvaceae mystery: A mallow maelstrom of genome multiplications and maybe misleading methods?

Previous research suggests that Gossypium has undergone a 5-to 6-fold multiplication following its divergence from Theobroma. However, the number of events, or where they occurred in the Malvaceae phylogeny remains unknown. We analyzed transcriptomic and genomic data from representatives of eight of the nine Malvaceae subfamilies. Phylogenetic analysis of nuclear data placed Dombeya(Dombeyoideae) as sister to the rest of Malvadendrina clade, but the plastid DNA tree strongly supported Durio(Helicteroideae) in this position. Intraspecific Ks plots indicated that all sampled taxa, except Theobroma(Byttnerioideae), Corchorus(Grewioideae), and Dombeya(Dombeyoideae), have experienced whole genome multiplications(WGMs). Quartet analysis suggested WGMs were shared by Malvoideae-Bombacoideae and Sterculioideae-Tilioideae, but did not resolve whether these are shared with each other or Helicteroideae(Durio).Gene tree reconciliation and Bayesian concordance analysis suggested a complex history. Alternative hypotheses are suggested, each involving two independent autotetraploid and one allopolyploid event. They differ in that one entails an allopolyploid origin for the Durio lineage,whereas the other invokes an allopolyploid origin for Malvoideae-Bombacoideae. We highlight the need for more genomic information in the Malvaceae and improved methods to resolve complex evolutionary histories that may include allopolyploidy, incomplete lineage sorting, and variable rates of gene and genome evolution.