Polylipid Nanoparticle, a Novel Lipid-Based Vector for Liver Gene Transfer

The clinical application of non-viral vector-based gene transfer has been hampered by less efficiency, short-term transgene expression and toxicity. Polylipid nanoparticles we have developed have been demonstrated to be highly efficient and non-toxic. The duration of effective transgene expression is long enough for a particular target window in liver disorders, such as drug toxicity, alcoholic liver injury and ischemia/reperfusion-associated donor organ damage. Moreover, a high DNA-packaging capacity, an extremely low binding rate to serum proteins, and amendable synthetic approaches for a large quantity of production confer this formulation of lipid-based transfer of antioxidant genes a great potential of clinical application. This chapter covers our experience in the synthesis, formulation, optimization and validation of the polylipid nanoparticle-mediated antioxidantgene transfer for the development of liver-based gene delivery approaches tailored for particular clinical scenarios. We also share our efforts and challenges faced in moving this potential gene transfer approach towards clinical application.

Photosynthetic Acclimation of Shade-Grown Soybean Seedlings to a High-Light Environment

Soybean in relay intercropping is initially exposed to a shade environment, followed by exposure to full sunlight after the harvesting of primary crops, e.g., maize. Therefore, soybean’s ability to acclimate to this changing light environment determines its growth and yield formation. However, the changes in soybean photosynthesis under such light alternations in relay intercropping are poorly understood. This study compared the photosynthetic acclimation of two soybean varieties with contrasting shade tolerance, i.e., Gongxuan1 (shade-tolerant) and C103 (shade-intolerant). The two soybean genotypes were grown in a greenhouse under full sunlight (HL) and 40% full sunlight (LL) conditions. Subsequently, after the fifth compound leaf expanded, half of the LL plants were transferred to a high-sunlight environment (LL-HL). Morphological traits were measured at 0 and 10 days, while chlorophyll content, gas exchange characteristics and chlorophyll fluorescence were assayed at 0, 2, 4, 7 and 10 days after transfer to an HL environment (LL-HL). Shade-intolerant C103 showed photoinhibition 10 days after transfer, and the net photosynthetic rate (Pn) did not completely recover to that under a high light level. On the day of transfer, the shade-intolerant variety, C103, exhibited a decrease in net photosynthetic rate (Pn), stomatal conductance (Gs) and transpiration rate (E) in the low-light (LL) and low-light-to-high-light (LL-HL) treatments. Additionally, intercellular CO2 concentration (Ci) increased in low light, suggesting that non-stomatal factors were the primary limitations to photosynthesis in C103 following the transfer. In contrast, the shade-tolerant variety, Gongxuan1, displayed a greater increase in Pn 7 days after transfer, with no difference observed between the HL and LL-HL treatments. Ten days after transfer, the shade-tolerant Gongxuan1 exhibited 24.1%, 10.9% and 20.9% higher biomass, leaf area and stem diameter than the intolerant C103. These findings suggest that Gongxuan1 possesses a higher capacity to adapt to variations in light conditions, making it a potential candidate for variety selection in intercropping systems

Syndromic Surveillance Systems for Mass Gatherings: A Scoping Review

Syndromic surveillance involves the near-real-time collection of data from a potential multitude of sources to detect outbreaks of disease or adverse health events earlier than traditional forms of public health surveillance. The purpose of the present study is to elucidate the role of syndromic surveillance during mass gathering scenarios. In the present review, the use of syndromic surveillance for mass gathering scenarios is described, including characteristics such as methodologies of data collection and analysis, degree of preparation and collaboration, and the degree to which prior surveillance infrastructure is utilized. Nineteen publications were included for data extraction. The most common data source for the included syndromic surveillance systems was emergency departments, with first aid stations and event-based clinics also present. Data were often collected using custom reporting forms. While syndromic surveillance can potentially serve as a method of informing public health policy regarding specific mass gatherings based on the profile of syndromes ascertained, the present review does not indicate that this form of surveillance is a reliable method of detecting potentially critical public health events during mass gathering scenarios

The Relationship between Addictive Use of Short-Video Platforms and Marital Satisfaction in Older Chinese Couples: An Asymmetrical Dyadic Process

Increasing evidence indicates that the addictive use of social media can have a detrimental effect on marital satisfaction, due mainly to the decrease in time and focus given to one's spouse. However, the impact of social media use among older couples remains under-investigated, and the research that does exist relies on individual-level data that do not allow the exploration of the dynamics between the dyadic partners. Therefore, the present study focused on older adults' use of short-video platforms, as these have been shown to be particularly addictive for older adults. A sample of 264 older couples was gathered (meanage = 68.02, SD = 8.68), and both spouses completed surveys reporting addictive use of short-video platforms, negative emotions, and marital satisfaction. Using an actor-partner interdependence model, we found an asymmetrical dyadic process in that the addictive use of short-video platforms by the wives was not only related to their own negative emotions, but also those of their spouse, as well as to decreased marital satisfaction. Meanwhile, addictive use by the husbands seemed to relate only to their own increased negative emotions, as well as to decreased marital satisfaction. Together, the findings from this study reveal dyadic dynamics with delineated pathways through which the addictive use of short-video platforms can damage older couples' interactive processes and marital satisfaction

Monocytes engineered with iSNAP inhibit human B-lymphoma progression.

Monocytes are important regulators for the maintenance of homeostasis in innate and adaptive immune system and have been reported to play important role in cancer progression. CD47-SIRPα recognition is a coinhibitory immune signal to inhibit phagocytosis in monocytes and macrophages and has been well-known as the "Don't eat me" signal. By using an approach of integrated sensing and activating proteins (iSNAPs), we have rewired the CD47-SIRPα axis to create iSNAP-M which activates pathways in engineered human monocytes (iSNAP-MC). The mRNA expression levels of the monocyte/macrophage markers CD11b, CD14, and CD31 are upregulated in iSNAP-monocytes (iSNAP-MC). With PMA induction, the iSNAP-MC-derived macrophages (iSNAP-MΦ) showed upregelation in CD86 and CD80, but not CD206. TNFα expression and secretion were also increased in iSNAP-MΦ. Furthermore, the injection of iSNAP-MC into mice bearing human B-lymphoma tumors led to the suppression of tumor progression. Therefore, the engineered monocytes, via blockage of coinhibitory immune signals by rewiring CD47-SIRPα axis, can be applied to suppress target tumors for cancer immunotherapy

Control of the activity of CAR-T cells within tumours via focused ultrasound.

Focused ultrasound can deliver energy safely and non-invasively into tissues at depths of centimetres. Here we show that the genetics and cellular functions of chimeric antigen receptor T cells (CAR-T cells) within tumours can be reversibly controlled by the heat generated by short pulses of focused ultrasound via a CAR cassette under the control of a promoter for the heat-shock protein. In mice with subcutaneous tumours, locally injected T cells with the inducible CAR and activated via focused ultrasound guided by magnetic resonance imaging mitigated on-target off-tumour activity and enhanced the suppression of tumour growth, compared with the performance of non-inducible CAR-T cells. Acoustogenetic control of the activation of engineered T cells may facilitate the design of safer cell therapies

Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression

Intra-articular injection of mesenchymal stem cells (MSCs) is a promising strategy for osteoarthritis (OA) treatment. However, more and more studies reveal that the injected MSCs have poor adhesion, migration, and survival in the joint cavity. A recent study shows that tropoelastin (TE) regulates adhesion, proliferation and phenotypic maintenance of MSCs as a soluble additive, indicating that TE could promote MSCs-homing in regenerative medicine. In this study, we used TE as injection medium, and compared it with classic media in MSCs intra-articular injection such as normal saline (NS), hyaluronic acid (HA), and platelet-rich plasma (PRP). We found that TE could effectively improve adhesion, migration, chondrogenic differentiation of infrapatellar fat pad MSCs (IPFP-MSCs) and enhance matrix synthesis of osteoarthritic chondrocytes (OACs) in indirect-coculture system. Moreover, TE could significantly enhance IPFP-MSCs adhesion via activation of integrin β1, ERK1/2 and vinculin (VCL) in vitro. In addition, intra-articular injection of TE-IPFP MSCs suspension resulted in a short-term increase in survival rate of IPFP-MSCs and better histology scores of rat joint tissues. Inhibition of integrin β1 or ERK1/2 attenuated the protective effect of TE-IPFP MSCs suspension in vivo. In conclusion, TE promotes performance of IPFP-MSCs and protects knee cartilage from damage in OA through enhancement of cell adhesion and activation of integrin β1/ERK/VCL pathway. Our findings may provide new insights in MSCs intra-articular injection for OA treatment

Expert recommendation on collection, storage, annotation, and management of data related to medical artificial intelligence

Medical artificial intelligence (AI) and big data technology have rapidly advanced in recent years, and they are now routinely used for image-based diagnosis. China has a massive amount of medical data. However, a uniform criteria for medical data quality have yet to be established. Therefore, this review aimed to develop a standardized and detailed set of quality criteria for medical data collection, storage, annotation, and management related to medical AI. This would greatly improve the process of medical data resource sharing and the use of AI in clinical medicine

Endothelial deletion of PTBP1 disrupts ventricular chamber development

Alternative splicing crucially affects various biological processes, however, its function in heart development is largely unknown. Here, the authors show an essential role of alternative splicing factor PTBP1 in ventricular chamber development