Advances in the design and development of SARS-CoV-2 vaccines.

Since the end of 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. The RNA genome of SARS-CoV-2, which is highly infectious and prone to rapid mutation, encodes both structural and nonstructural proteins. Vaccination is currently the only effective method to prevent COVID-19, and structural proteins are critical targets for vaccine development. Currently, many vaccines are in clinical trials or are already on the market. This review highlights ongoing advances in the design of prophylactic or therapeutic vaccines against COVID-19, including viral vector vaccines, DNA vaccines, RNA vaccines, live-attenuated vaccines, inactivated virus vaccines, recombinant protein vaccines and bionic nanoparticle vaccines. In addition to traditional inactivated virus vaccines, some novel vaccines based on viral vectors, nanoscience and synthetic biology also play important roles in combating COVID-19. However, many challenges persist in ongoing clinical trials.

Marine-Derived Collagen as Biomaterials for Human Health.

Collagen is a kind of biocompatible protein material, which is widely used in medical tissue engineering, drug delivery, cosmetics, food and other fields. Because of its wide source, low extraction cost and good physical and chemical properties, it has attracted the attention of many researchers in recent years. However, the application of collagen derived from terrestrial organisms is limited due to the existence of diseases, religious beliefs and other problems. Therefore, exploring a wider range of sources of collagen has become one of the main topics for researchers. Marine-derived collagen (MDC) stands out because it comes from a variety of sources and avoids issues such as religion. On the one hand, this paper summarized the sources, extraction methods and characteristics of MDC, and on the other hand, it summarized the application of MDC in the above fields. And on the basis of the review, we found that MDC can not only be extracted from marine organisms, but also from the wastes of some marine organisms, such as fish scales. This makes further use of seafood resources and increases the application prospect of MDC.

Fenton Reaction Induced by Fe-Based Nanoparticles for Tumor Therapy.

Fenton reaction, a typical inorganic reaction, is broadly utilized in the field of wastewater treatment. Recently In case of its ability to inhibit the growth of cancer cells, it has been frequently reported in cancer treatment. Using the unique tumor microenvironment in cancer cells, many iron-based nanoparticles have been developed to release iron ions in cancer cells to induce Fenton reaction. In this mini review, we outline several different types of iron-based nanoparticles and several main means to enhance Fenton reaction in cancer cells. Finally, we discussed the advantages and disadvantages of iron-based nanoparticles for cancer therapy, prospected the future development of iron-based nanoparticles. It is believed that iron-based nanoparticles can make certain contribution to the cause of human cancer in the future.

3D bioactive cell-free-scaffolds for in-vitro/in-vivo capture and directed osteoinduction of stem cells for bone tissue regeneration.

Hydrophilic bone morphogenetic protein 2 (BMP2) is easily degraded and difficult to load onto hydrophobic carrier materials, which limits the application of polyester materials in bone tissue engineering. Based on soybean-lecithin as an adjuvant biosurfactant, we designed a novel cell-free-scaffold of polymer of poly(ε-caprolactone) and poly(lactide-co-glycolide)-co-polyetherimide with abundant entrapped and continuously released BMP2 for in vivo stem cell-capture and in situ osteogenic induction, avoiding the use of exogenous cells. The optimized bioactive osteo-polyester scaffold (BOPSC), i.e. SBMP-10SC, had a high BMP2 entrapment efficiency of 95.35%. Due to its higher porosity of 83.42%, higher water uptake ratio of 850%, and sustained BMP2 release with polymer degradation, BOPSCs were demonstrated to support excellent in vitro capture, proliferation, migration and osteogenic differentiation of mouse adipose derived mesenchymal stem cells (mADSCs), and performed much better than traditional BMP-10SCs with unmodified BMP2 and single polyester scaffolds (10SCs). Furthermore, in vivo capture and migration of stem cells and differentiation into osteoblasts was observed in mice implanted with BOPSCs without exogenous cells, which enabled allogeneic bone formation with a high bone mineral density and ratios of new bone volume to existing tissue volume after 6 months. The BOPSC is an advanced 3D cell-free platform with sustained BMP2 supply for in situ stem cell capture and osteoinduction in bone tissue engineering with potential for clinical translation.

Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons.

Neurogenesis in the developing neocortex begins with the generation of the preplate, which consists of early-born neurons including Cajal-Retzius (CR) cells and subplate neurons. Here, utilizing the Ebf2-EGFP transgenic mouse in which EGFP initially labels the preplate neurons then persists in CR cells, we reveal the dynamic transcriptome profiles of early neurogenesis and CR cell differentiation. Genome-wide RNA-seq and ChIP-seq analyses at multiple early neurogenic stages have revealed the temporal gene expression dynamics of early neurogenesis and distinct histone modification patterns in early differentiating neurons. We have identified a new set of coding genes and lncRNAs involved in early neuronal differentiation and validated with functional assays in vitro and in vivo. In addition, at E15.5 when Ebf2-EGFP+ cells are mostly CR neurons, single-cell sequencing analysis of purified Ebf2-EGFP+ cells uncovers molecular heterogeneities in CR neurons, but without apparent clustering of cells with distinct regional origins. Along a pseudotemporal trajectory these cells are classified into three different developing states, revealing genetic cascades from early generic neuronal differentiation to late fate specification during the establishment of CR neuron identity and function. Our findings shed light on the molecular mechanisms governing the early differentiation steps during cortical development, especially CR neuron differentiation.

Osteogenic differentiation system based on biopolymer nanoparticles for stem cells in simulated microgravity.

An efficient long-term intracellular growth factor release system in simulated microgravity for osteogenic differentiation was prepared based on polylactic acid (PLA) and polyhydroxyalkanoate (PHA) nanoparticles (NPs) for loading of bone morphogenetic protein 2 (BMP2) and bone morphogenetic protein 7 (BMP7) (defined as sB2-PLA-NPs and sB7-PHA-NPs), respectively, associated with osteogenic differentiation of human adipose derived stem cells (hADSCs). On account of soybean lecithin (SL) as biosurfactants, sB2-PLA-NPs and sB7-PHA-NPs had a high encapsulation efficiency (>80%) of BMPs and uniform small size (<100 nm), and showed a different slow-release to provide BMP2 in early stage and BMP7 in late stages of osteogenic differentiation within 20 d, due to degradation rate of PLA and PHA in cells. After uptake into hADSCs, by comparison with single sB2-PLA-NPs or sB7-PHA-NPs, the Mixture NPs compound of sB2-PLA-NP and sB7-PHA-NP with a mass ratio of 1:1, can well-promote ALP activity, expression of OPN and upregulated related osteo-genes. Directed osteo-differentiation of mixture NPs was similar to result of sustained free-BMP2 and BMP7-supplying (sFree-B2&B7) in simulated microgravity, which demonstrated the reliability and stability of Mixture NPs as a long-term osteogenic differentiation system in space medicine and biology in future.

Surgical treatment for rabbits' femoral arteries subjected to gunshot wounds combining with seawater immersion.

OBJECTIVE: To investigate the surgical treatment methods and evaluate the outcome of gunshot wounds combining with seawater immersion in rabbits' femoral arteries. METHODS: One hundred healthy New Zealand white rabbits (either sex, 3.14 kg+/-0.61 kg in weight) were randomly divided into a seawater immersion group (n=50) and a simple injury group (n=50). The unilateral femoral arteries of all the rabbits were injured by 0.38 g steel spheres with velocity of 600-800 m/s fired by a 7.62 mm rifle. The rabbits in the seawater immersion group were immersed in seawater (saline content of 2.54%, pH 8.2-8.4, and at 21 degrees C) for 60 minutes but those in the simple injury group were not. After the injured segment (observed by naked eyes) of the femoral artery was excised, the blood flow restoration was reconstructed by direct end-to-end anastomosis, reversed autogenous venous grafting or cryopreserved arterial allografting, according to the length of the arterial defects. At 24 hours, and 7, 14 and 21 days after operation, the blood flow was examined. Operative exploration was performed for the animals with partly or fully obstructed blood flow. The tissues around the anastomosis sites and the grafts were harvested for pathological observation under a light microscope and an electron microscope. RESULTS: In the rabbits with completely transected injury, the unobstructed rates in the first 3 weeks after operation were 80.00% in the seawater immersion group and 86.67% in the single injury group, and no significant difference was found between the two groups (P>0.1). In the rabbits with arterial contusion injury, the unobstructed rates in the first 3 weeks after operation were 86.67% in the seawater immersion group and 82.35% in the single injury group, and no significant difference was found between the two groups (P>0.1). Most thrombosis occurred in the first operative week. Atypical endothelial cells were detected at the anastomosis sites at the first operative week, and the anastomosis sites were lined with endothelial cells in 3 weeks postoperatively. CONCLUSIONS: During the surgical treatment for gunshot wounds combining with seawater immersion, resection of the grossly-injured artery and routine artery reconstruction can obtain satisfactory outcome. Homologous artery is a kind of vascular graft with certain applied value.

Pathological study of rabbits' femoral arteries subjected to gunshot wounds combining with seawater immersion.

OBJECTIVE: To investigate pathological characteristics of gunshot wounds concomitant seawater immersion in rabbits' femoral arteries. METHODS: Thirty rabbits were divided randomly into 3 groups: simple gunshot-wound group (Group I, n = 10), gunshot wound with seawater immersion for 30 mins (Group II, n = 10), and 60 mins group (Group III, n = 10). Femoral arteries were impacted by 0.38 g steel spheres fired with a 7.62 mm rifle. After being wounded, rabbits in Groups II and III were immersed in seawater for 30 or 60 mins, but those in Group I were not. At 2, 4, 6, 8, 12 hours following injury, a 40 mm segment of the artery on each side of the gunshot point were excised and observed by light and electron microscopy. RESULTS: The patterns of arterial injuries were mainly contusion and transection. Completely transected artery was classified as primary-wound-tract area, contused area and shocked area. Compared with those in Group I, the primary-wound-tract and contused areas in Group II manifested obvious swelling in the arterial wall especially at the outside 2/3 of the media. Vacuolar structures were often seen in smooth muscle cells of the media. Intercellular space among the smooth muscle cells were filled with homogeneous acidophilic substances. Deep rugae among endothelial cells flattened or rugal folds lost their longitudinal orientation, and marked fibrin and platelet deposition were noticed. No significant difference was detected between Group II and III. The pathological changes in the shocked area were similar in 3 groups. CONCLUSIONS: For gunshot wounds concomitant seawater immersion in rabbits' femoral arteries, there was a marked swelling of cells and intercellular space in primary-wound-tract area and contusion area. The influence of these pathological changes on surgical reparation deservers further study.