Liquid-phase 3D bioprinting of gelatin alginate hydrogels:influence of printing parameters on hydrogel line width and layer height

Extrusion-based 3D bioprinting is a direct deposition approach used to create three-dimensional(3D)tissue scaffolds typically comprising hydrogels.Hydrogels are hydrated polymer networks that are chemically or physically cross-linked.Often,3D bioprinting is performed in air,despite the hydrated nature of hydrogels and the potential advantage of using a liquid phase to provide cross-linking and otherwise functionalize the hydrogel.In this work,we print gelatin alginate hydrogels directly into a cross-linking solution of calcium chloride and investigate the influence of nozzle diameter,distance between nozzle and surface,calcium chloride concentration,and extrusion rate on the dimensions of the printed hydrogel.The hydrogel layer height was generally found to increase with increasing extrusion rate and nozzle distance,according to the increased volume extruded and the available space,respectively.In addition,the hydrogel width was generally found to increase with decreasing nozzle distance and cross-linking concentration corresponding to confinement-induced spreading and low crosslinking regimes,respectively.Width/height ratios of^1 were generally achieved when the nozzle diameter and distance were comparable above a certain cross-linking concentration.Using these relationships,biocompatible 3D multilayer structures were successfully printed directly into calcium chloride cross-linking solution.

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.

Growth and differentiation of human induced pluripotent stem cell(hiPSC)-derived kidney organoids using fully synthetic peptide hydrogels

Human induced pluripotent stem cell(hiPSC)-derived kidney organoids have prospective applications ranging from basic disease modelling to personalised medicine.However,there remains a necessity to refine the bio-physical and biochemical parameters that govern kidney organoid formation.Differentiation within fully-controllable and physiologically relevant 3D growth environments will be critical to improving organoid reproducibility and maturation.Here,we matured hiPSC-derived kidney organoids within fully synthetic self-assembling peptide hydrogels(SAPHs)of variable stiffness(storage modulus,G′).The resulting organoids con-tained complex structures comparable to those differentiated within the animal-derived matrix,Matrigel.Single-cell RNA sequencing(scRNA-seq)was then used to compare organoids matured within SAPHs to those grown within Matrigel or at the air-liquid interface.A total of 13,179 cells were analysed,revealing 14 distinct clusters.Organoid compositional analysis revealed a larger proportion of nephron cell types within Transwell-derived organoids,while SAPH-derived organoids were enriched for stromal-associated cell populations.Notably,dif-ferentiation within a higher G’SAPH generated podocytes with more mature gene expression profiles.Addi-tionally,maturation within a 3D microenvironment significantly reduced the derivation of off-target cell types,which are a known limitation of current kidney organoid protocols.This work demonstrates the utility of syn-thetic peptide-based hydrogels with a defined stiffness,as a minimally complex microenvironment for the selected differentiation of kidney organoids.

The Yin and Yang of the protein corona on the delivery journey of nanoparticles

Nanoparticles-based drug delivery systems have attracted significant attention in biomedical fields because they can deliver loaded cargoes to the target site in a controlled manner.However,tremendous challenges must still be overcome to reach the expected targeting and therapeutic efficacy in vivo.These challenges mainly arise because the interaction between nanoparticles and biological systems is complex and dynamic and is influenced by the physicochemical properties of the nanoparticles and the heterogeneity of biological systems.Importantly,once the nanoparticles are injected into the blood,a protein corona will inevitably form on the surface.The protein corona creates a new biological identity which plays a vital role in mediating the bio–nano interaction and determining the ultimate results.Thus,it is essential to understand how the protein corona affects the delivery journey of nanoparticles in vivo and what we can do to exploit the protein corona for better delivery efficiency.In this review,we first summarize the fundamental impact of the protein corona on the delivery journey of nanoparticles.Next,we emphasize the strategies that have been developed for tailoring and exploiting the protein corona to improve the transportation behavior of nanoparticles in vivo.Finally,we highlight what we need to do as a next step towards better understanding and exploitation of the protein corona.We hope these insights into the“Yin and Yang”effect of the protein corona will have profound implications for understanding the role of the protein corona in a wide range of nanoparticles.

Prevention and treatment of viral respiratory infections by traditional Chinese herbs

Objective This review focuses on current knowledge of traditional Chinese herbs on prevention and treatment of viral respiratory infections,especially caused by Severe Acute Respiratory Syndromes （SARS） virus,respiratory syncytial virus （RSV） and influenza viruses.Data sources The data used in this review were obtained from PubMed and CNKI up to May 2013.Terms of Chinese herbs and infections of respiratory tract were used in the search.Study selection Articles related that Chinese herbs preventing and treating infections in respiratory tract were retrieved and reviewed.The risk of bias of included studies was assessed by the method in the ＂Cochrane Handbook of Systematic Reveiws of Interventionsand studies＂ with high risk of bias were excluded.Four criteria for selections were set as following：randomized controlled trial,particular effective compound or derivative,reproducible result and animal test.Results Infectious respiratory tract diseases cause most mortality among infectious illnesses around the world.As traditional medicines,Chinese herbs have been widely used to deal with diseases for centuries and have been proved effective in practice.The administration of some Chinese herbs stimulates,suppresses or regulates the activity of immune system,thus protecting the respiratory tract or relieving infections of pathogens.Many herbs have remarkable antiviral effects,therefore they are used as substitutes of antimicrobial drugs.Based on the theory of traditional Chinese medicine,mix-using herbs provide a synergistic benefit on preventing and healing respiratory tract infections.Many commercial herbal medicines containing one or more compounds have been successfully applied to prevent and treat viral infections of respiratory tract clinically.Conclusions Traditional Chinese herbs could directly inhibit pathogens infecting respiratory tract,or coordinate the activity of immune system to avoid or relieve infections.With the emergence of antidrug pathogens or new variants,Chinese herbs.give strong evidence to protect human health.

The role of chemokines in acute and chronic hepatitis C infection

Hepatitis C imposes a significant burden on global healthcare. Chronic infection is associated with progressive inflammation of the liver which typically manifests in cirrhosis, organ failure and cancer. By virtue of elaborate evasion strategies, hepatitis C virus （HCV） succeeds as a persistent human virus. It has an extraordinary capacity to subvert the immune response enabling it to establish chronic infections and associated liver disease. Chemokines are low molecular weight chemotactic peptides that mediate the recruitment of inflammatory cells into tissues and back into the lymphatics and peripheral blood. Thus, they are central to the temporal and spatial distribution of effector and regulatory immune cells. The interactions between chemokines and their cognate receptors help shape the immune response and therefore, have a major influence on the outcome of infection. However, chemokines represent a target for modulation by viruses including the HCV. HCV is known to modulate chemokine expression in vitro and may therefore enable its survival by subverting the immune response in vivo through altered leukocyte chemotaxis resulting in impaired viral clearance and the establishment of chronic low-grade inflammation. In this review, the roles of chemokines in acute and chronic HCV infection are described with a particular emphasis placed on chemokine modulation as a means of immune subversion. We provide an in depth discussion of the part played by chemokines in mediating hepatic fibrosis while addressing the potential applications for these chemoattractants in prognostic medicine.

Performance assessment and microbial diversity of two pilot scale multi-stage sub-surface flow constructed wetland systems

This study assessed the performance and diversity of microbial communities in multi-stage sub-surface flow constructed wetland systems（CWs）. Our aim was to assess the impact of configuration on treatment performance and microbial diversity in the systems. Results indicate that at loading rates up to 100 g BOD5/（m2·day）, similar treatment performances can be achieved using either a 3 or 4 stage configuration. In the case of phosphorus（P）, the impact of configuration was less obvious and a minimum of 80% P removal can be expected for loadings up to 10 g P/（m2·day） based on the performance results obtained within the first16 months of operation. Microbial analysis showed an increased bacterial diversity in stage four compared to the first stage. These results indicate that the design and configuration of multi-stage constructed wetland systems may have an impact on the treatment performance and the composition of the microbial community in the systems, and such knowledge can be used to improve their design and performance.

Roles for the VCP co-factors Npl4 and Ufd1 in neuronal function in Drosophila melanogaster

The VCP-Ufd1-Npl4 complex regulates proteasomal processing within cells by delivering ubiquitinated proteins to the proteasome for degradation.Mutations in VCP are associated with two neurodegenerative diseases,amyotrophic lateral sclerosis（ALS） and inclusion body myopathy with Paget＇s disease of the bone and frontotemporal dementia（IBMPFD）,and extensive study has revealed crucial functions of VCP within neurons.By contrast,little is known about the functions of Npl4 or Ufd1 in vivo.Using neuronalspecific knockdown of Npl4 or Ufd1 in Drosophila melanogaster,we infer that Npl4 contributes to microtubule organization within developing motor neurons.Moreover,Npl4 RNAi flies present with neurodegenerative phenotypes including progressive locomotor deficits,reduced lifespan and increased accumulation of TAR DNA-binding protein-43 homolog（TBPH）.Knockdown,but not overexpression,of TBPH also exacerbates Npl4 RNAi-associated adult-onset neurodegenerative phenotypes.In contrast,we find that neuronal knockdown of Ufd1 has little effect on neuromuscular junction（NMJ） organization,TBPH accumulation or adult behaviour.These findings suggest the differing neuronal functions of Npl4 and Ufd1 in vivo.

Innate endogenous adjuvants prime to desirable immune responses via mucosal routes

Vaccination is an effective strategy to prevent infectious or immune related diseases, which has made remarkable contribution in human history. Recently increasing atten- tions have been paid to mucosal vaccination due to its multiple advantages over conventional ways. Subunit or peptide antigens are more reasonable immunogens for mucosal vaccination than live or attenuated pathogens, however adjuvants are required to augment the immune responses. Many mucosal adjuvants have been developed to prime desirable immune responses to different etiologies. Compared with pathogen derived adjuvants, innate endogenous molecules incorporated into mucosal vaccines demonstrate prominent adjuvanticity and safety. Nowadays, cytokines are broadly used as mucosal adjuvants for participation of signal transduction of immune responses, activation of innate immunity and polarization of adaptive immunity. Desired immune responses are promptly and efficaciously primed on basis of specific interactions between cytokines and corresponding receptors. In addition, some other innate molecules are also identified as potent mucosal adjuvants. This review focuses on innate endogenous mucosal adjuvants, hoping to shed light on the development of mucosal vaccines.