Open Design and 3D Printing of Face Shields: The Case Study of a UK-China Initiative

At the start of the COVID-19 outbreak, many countries lacked personal protective equipment (PPE) to protect healthcare workers. To address this problem, open design and 3D printing technologies were adopted to provide much-in-need PPEs for key workers. This paper reports an initiative by designers and engineers in the UK and China. The case study approach and content analysis method were used to study the stakeholders, the design process, and other relevant issues such as regulation. Good practice and lessons were summarised, and suggestions for using distributed 3D printing to supply PPEs were made. It concludes that 3D printing has played an important role in producing PPEs when there was a shortage of supply, and distributed manufacturing has the potential to quickly respond to local small-bench production needs. In the future, clearer specification, better match of demands and supply, and quicker evaluation against relevant regulations will provide efficiency and quality assurance for 3D printed PPE supplies

Self‐Assembly of Therapeutic Peptide into Stimuli‐Responsive Clustered Nanohybrids for Cancer‐Targeted Therapy

Clinical translation of therapeutic peptides, particularly those targeting intracellular protein–protein interactions (PPIs), has been hampered by their inefficacious cellular internalization in diseased tissue. Therapeutic peptides engineered into nanostructures with stable spatial architectures and smart disease targeting ability may provide a viable strategy to overcome the pharmaceutical obstacles of peptides. This study describes a strategy to assemble therapeutic peptides into a stable peptide–Au nanohybrid, followed by further self‐assembling into higher‐order nanoclusters with responsiveness to tumor microenvironment. As a proof of concept, an anticancer peptide termed β‐catenin/Bcl9 inhibitors is copolymerized with gold ion and assembled into a cluster of nanohybrids (pCluster). Through a battery of in vitro and in vivo tests, it is demonstrated that pClusters potently inhibit tumor growth and metastasis in several animal models through the impairment of the Wnt/β‐catenin pathway, while maintaining a highly favorable biosafety profile. In addition, it is also found that pClusters synergize with the PD1/PD‐L1 checkpoint blockade immunotherapy. This new strategy of peptide delivery will likely have a broad impact on the development of peptide‐derived therapeutic nanomedicine and reinvigorate efforts to discover peptide drugs that target intracellular PPIs in a great variety of human diseases, including cancer.A strategy for clinical translation of therapeutic peptides by assembling them into a stable peptide–Au nanohybrid, followed by further self‐assembling into higher‐order nanoclusters with responsiveness to the tumor microenvironment, is presented. An anticancer peptide termed β‐catenin/Bcl9 inhibitor is assembled into a cluster of nanohybrids termed pCluster, which potently inhibits tumor growth as well as metastasis, and synergizes with immunotherapy, while maintaining a highly favorable biosafety profile.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148246/1/adfm201807736.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148246/2/adfm201807736-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148246/3/adfm201807736_am.pd

Promotion of angiogenesis and suppression of inflammatory response in skin wound healing using exosome-loaded collagen sponge

Effectively promoting skin wound healing remains a significant challenge in the medical field. Although stem cell-derived exosomes show potential in tissue regeneration, their local delivery and sustained release face challenges. To address these issues, we developed a collagen sponge based on type I and recombinant humanized type III collagen. Our study confirmed that exosomes were successfully loaded onto the sponge (sponge-Exo) and the sponge-Exo gradually released exosomes into the local milieu. The sponge-Exo played a crucial role in promoting the transition of macrophages from an inflammatory M1 phenotype to a regenerative M2 phenotype. Moreover, it enhanced the migration and proliferation of HDFs and promoted angiogenesis in HUVECs. Additionally, our findings revealed that the sponge-Exo accelerated wound healing by suppressing inflammatory response and stimulating angiogenesis in a rat full-thickness skin wounds model. Next generation sequencing (NGS) was used to explore the underlying mechanism of wound healing, and the results showed that the miRNAs (hsa-miR-21-5p and hsa-miR-29a-5p) associated with wound healing in exosomes were significantly up-regulated. These results highlight the remarkable effects of sponge-Exo on macrophage transformation, cell migration, proliferation and angiogenesis, which provide a potential prospect for the application in the field of skin wound healing

Hypertension moderates the relationship between plasma beta-amyloid and cognitive impairment: a cross-sectional study in Xi’an, China

BackgroundPlasma beta-amyloid (Aβ) are important biomarkers for Alzheimer’s disease and cognitive impairment (CI), but results are controversial. It remains unclear whether hypertension modulates their relationship. This cross-sectional study investigates whether hypertension moderates the relationship between plasma Aβ and cognitive impairment (CI).MethodsThis cross-sectional study included 1488 subjects ≥ 40 years from rural areas of northwestern China. CI was defined as a Mini-Mental State Examination score lower than the cutoff. Firstly, plasma Aβ40, Aβ42, Aβ42/Aβ40 were analyzed as restricted cubic spline. Then, categories of combined plasma Aβ were created by making bisection of plasma Aβ according to average and combining them as L-Aβ40 and L-Aβ42, H-Aβ40 and L-Aβ42, L-Aβ40 and H-Aβ42, H-Aβ40 and H-Aβ42. Decreased plasma Aβ40 was defined as < 25th percentile. Multivariate logistic regression examined the relationship between plasma Aβ and CI in total population, the hypertension subgroup and the non-hypertension subgroup.Results737 participants (49.5%) had hypertension and 189 participants (12.7%) had CI. Simultaneously elevated plasma Aβ40 and Aβ42 was associated with CI in hypertension (H-Aβ40 and H-Aβ42 vs. L-Aβ40 and L-Aβ42, 21.1% vs.10.7%, P = 0.033; OR = 1.984 [95% CI, 1.067–3.691], P = 0.030) but not in the non-hypertension. Decreased plasma Aβ40 was associated with CI in the non-hypertension (14.9% vs. 9.2%, P = 0.026; OR = 1.728 [95% CI, 1.018–2.931], P = 0.043) but not in the hypertension.ConclusionHypertension is an important modulator in the relationship between plasma Aβ and CI. Simultaneously elevated plasma Aβ40 and Aβ42 in the hypertension, and decreased plasma Aβ40 in the non-hypertension, may be risk factors for CI. These findings emphasize the need to consider hypertension in CI detection

The Valuation and Analysis of Apple Inc

In order to define a reasonable value of Apple’s stocks, a number of valuation models can be considered, including FCFF model, DDM, VC method, FCFE model and multiples valuation model. In the research, we use WACC and DCF calculation to evaluate the Apple company’s further value, and judging whether it is undervalued or overvalued based on historical data and market direction. As different models and data provide various results, they have different limitations and uses. For DCF, although some of the data used in its calculations are based on people's subjective analysis of the future, its valuation serves as a baseline for the target price, making its results relatively conservative and reasonable. Based on the results generated by valuation models, we think Apple still has a great potential to develop, and we advise customers to buy or hold the stock.</jats:p

Analysis of clinical manifestations and MRI features in multiple sclerosis involved with spinal cord

Objective To analyse the significance of clinical manifestations and magnetic resonance imaging (MRI) features in clinical diagnosis of multiple sclerosis (MS) involved with spinal cord. Methods The clinical data and MRI features of 46 inpatients with spinal cord involvement of multiple sclerosis from January 2006 to December 2009 were analysed retrospectively. Results The main onset type of the patients was acute (58.70% , 27/46) or sub ⁃ acute (34.78% , 16/46). The main clinical manifestations were acroparalysis (95.65%, 44/46), sensory disturbance (84.78%, 39/46) and retention of urine (67.39%, 31/46). MRI showed that cervical involvement was most common (45.65%, 21/46) which was followed by thoracic involvement (28.26% , 13/46). Single or multiple scattered long T1 and T2 abnormal signal patches were seen, and the lesion often involved 2 or less than 2 vertebrae (84.78%, 39/46) and might involve more than 2 vertebral segments (15.22%, 7/46). Different signal intensity was seen on enhanced scanning. Conclusion The clinical manifestations of patients with multiple sclerosis involved spinal cord are diverse. MRI shows that spinal cord involvement presents single or multiple lesions which usually do not involve more than 2 vertebral segments. Even if the lesion segment is extended, multiple sclerosis can not be excluded. MRI is the most sensitive and most specific imaging method to diagnose multiple sclerosis involved spinal cord. DOI：10.3969/j.issn.1672-6731.2011.01.02