Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

Motor neuron replacement therapy for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a motor neuron degenerative disease that is also known as Lou Gehrig’s disease in the United States,Charcot’s disease in France,and motor neuron disease in the UK.The loss of motor neurons causes muscle wasting,paralysis,and eventually death,which is commonly related to respiratory failure,within 3-5 years after onset of the disease.Although there are a limited number of drugs approved for amyotrophic lateral sclerosis,they have had little success at treating the associated symptoms,and they cannot reverse the course of motor neuron degeneration.Thus,there is still a lack of effective treatment for this debilitating neurodegenerative disorder.Stem cell therapy for amyotrophic lateral sclerosis is a very attractive strategy for both basic and clinical researchers,particularly as transplanted stem cells and stem cell-derived neural progenitor/precursor cells can protect endogenous motor neurons and directly replace the lost or dying motor neurons.Stem cell therapies may also be able to re-establish the motor control of voluntary muscles.Here,we review the recent progress in the use of neural stem cells and neural progenitor cells for the treatment of amyotrophic lateral sclerosis.We focus on MN progenitor cells derived from fetal central nervous system tissue,embryonic stem cells,and induced pluripotent stem cells.In our recent studies,we found that transplanted human induced pluripotent stem cell-derived motor neuron progenitors survive well,differentiate into motor neurons,and extend axons into the host white matter,not only in the rostrocaudal direction,but also along motor axon tracts towards the ventral roots in the immunodeficient rat spinal cord.Furthermore,the significant motor axonal extension after neural progenitor cell transplantation in amyotrophic lateral sclerosis models demonstrates that motor neuron replacement therapy could be a promising therapeutic strategy for amyotrophic lateral sclerosis,particularly as a variety of stem cell derivatives,including induced pluripotent stem cells,are being considered for clinical trials for various diseases.

Development of an integrated process for the production of high-purityγ-aminobutyric acid from fermentation broth

γ-Aminobutyric acid(GABA),a natural non-protein amino acid,plays an irreplaceable role in regulating the life activities of organisms.Nowadays,the separation and purification of food-grade GABA from fermentation broth is still a great challenge.This research utilized monosodium glutamate as a substrate for the production of high-purity GABA via an integrated process incorporating fermentation,purification,and crystallization.Firstly,147 g·L^(-1) GABA with a yield of 99.8%was achieved through fed-batch fermentation by Lactobacillus brevis CE701.Secondly,three integrated purification methods by ethanol precipitation were compared,and crude GABA with a purity of 89,85%was obtained by the optimized method.Thirdly,GABA crystals with a purity of 98.69%and a yield of 60%were further obtained through a designed crystallization process.Furthermore,the GABA industrial production process model was established by Superproper Designer V10 software,and material balance and economic analysis were carried out.Ethanol used in the process was recovered with a recovery of 98.79%through Aspen simulated extractive distillation.Then the fixed investment(equipment purchase and installation costs)for an annual production of 80 t GABA will be about 833000 USD;the total annual production cost(raw material cost and utility cost)will be about 641000 USD.The annual sale of GABA may be at the range of 2400000-4000000 USD and the payback period will be about 1-2 year.This integrated process provides a potential way for the industrial-scale production of food-grade GABA.

Image Fusion Real-time System Based on FPGA and Multi-DSP

In order to solve complex algorithm that is difficult to achieve real-time processing of Multiband image fusion within large amount of data, a real-time image fusion system based on FPGA and multi-DSP is designed. Five-band image acquisition, image registration, image fusion and display output can be done within the system which uses FPGA as the main processor and the other three DSP as an algorithm processor. Making full use of Flexible and high-speed characteristics of FPGA, while an image fusion algorithm based on multi-wavelet transform is optimized and applied to the system. The final experimental results show that the frame rate of 15 Hz, with a resolution of 1392 × 1040 of the five-band image can be used by the system to complete processing within 41ms.

A Self-Biomineralized Novel Adenovirus Vectored COVID-19 Vaccine for Boosting Immunization of Mice

SARS-CoV-2 has caused more than 3.8 million deaths worldwide,and several types of COVID-19 vaccines are urgently approved for use,including adenovirus vectored vaccines.However,the thermal instability and pre-existing immunity have limited its wide applications.To circumvent these obstacles,we constructed a self-biomineralized adenovirus vectored COVID-19 vaccine(Sad23L-n Co V-S-Ca P)by generating a calcium phosphate mineral exterior(Ca P)based on Sad23L vector carrying the full-length gene of SARS-Co V-2 spike protein(S)under physiological condition.This Sad23L-n Co V-S-Ca P vaccine was examined for its characteristics of structure,thermostability,immunogenicity and avoiding the problem of preexisting immunity.In thermostability test,Sad23L-n Co V-S-Ca P could be stored at 4°C for over 45 days,26°C for more than 8 days and 37°C for approximately 2 days.Furthermore,Sad23L-n Co V-S-Ca P induced higher level of S-specific antibody and T cell responses,and was not affected by the pre-existing anti-Sad23L immunity,suggesting it could be used as boosting immunization on Sad23L-n Co V-S priming vaccination.The boosting with Sad23L-n Co V-S-Ca P vaccine induced high titers of 10^(5.01)anti-S1,10^(4.77)anti-S2 binding antibody,10^(3.04) pseudovirus neutralizing antibody(IC_(50)),and robust T-cell response of IFN-c(1466.16 SFCs/10^(6)cells)to S peptides,respectively.In summary,the selfbiomineralization of the COVID-19 vaccine Sad23L-n Co V-S-Ca P improved vaccine efficacy,which could be used in prime-boost regimen for prevention of SARS-Co V-2 infection in humans.