Tissue Engineering in Neuroscience: Applications and Perspectives

Neurological disorders have always been a threat to human physical and mental health nowadays,which are closely related to the nonregeneration of neurons in the nervous system(NS).The damage to the NS is currently difficult to repair using conventional therapies,such as surgery and medication.Therefore,repairing the damaged NS has always been a vast challenge in the area of neurology.Tissue engineering(TE),which integrates the cell biology and materials science to reconstruct or repair organs and tissues,has widespread applications in bone,periodontal tissue defects,skin repairs,and corneal transplantation.Recently,tremendous advances have been made in TE regarding neuroscience.In this review,we summarize TE’s recent progress in neuroscience,including pathological mechanisms of various neurological disorders,the concepts and classification of TE,and the most recent development of TE in neuroscience.Lastly,we prospect the future directions and unresolved problems of TE in neuroscience.

Literature study on clinical treatment of facial paralysis in the last 20 years using Web of Science Comparison between rehabilitation, physiotherapy and acupuncture

BACKGROUND： Facial paralysis is defined as severe or complete loss of facial muscle motor function. OBJECTIVE： The study was undertaken to explore a bibliometric approach to quantitatively assess the research on clinical treatment of facial paralysis using rehabilitation, physiotherapy and acupuncture using Web of Science from 1992 to 2011. DESIGN： Bibliometric approach. DATA RETRIEVAL： A bibliometric analysis based on the publications on Web of Science was performed using key words such as ＂facial paralysis＂, ＂rehabilitation＂, ＂physiotherapy＂ and ＂acupuncture＂. INCLUSIVE CRITERIA： （1） Research articles on the clinical treatment of facial paralysis using acupuncture or physiotherapy （e.g. exercise, electro-stimulation） and other rehabilitation methods; （2） researches on human and animal fundamentals, clinical trials and case reports; （3） Article types： article, review, proceedings paper, note, letter, editorial material, discussion, book chapter. （4） Publication year： 1992-2011 inclusive. Exclusion criteria： （1）Articles on the causes and diagnosis on facial paralysis; （2） Type of articles： correction; （3） Articles from following databases： all databases related to social science and chemical databases in Web of Science. MAIN OUTCOME MEASURES： （1） Overall number of publications; （2） number of publications annually; （3） number of citations received annually; （4） top cited paper; （5） subject categories of publication; （6） the number of countries in which the article is published; （7） distribution of output in journals. RESULTS： Overall population stands at 3 543 research articles addressing the clinical treatment of facial paralysis in Web of Science during the study period. There is also a markedly increase in the number of publications on the subject ＂facial paralysis treatments using rehabilitation＂ during the first decade of the 21 st century, except in 2004 and 2006 when there are perceptible drops in the number of articles published. The only other year during the study period saw such a drop is 1993. Specifically, there are 192 published articles on facial paralysis treated by rehabilitation in the past two decades, far more than the output of physiotherapy treatment. Physiotherapy treatment scored only 25 articles including acupuncture treatment, with over 80% of these written by Chinese researchers and clinicians. Ranked by regions, USA is by far the most productive country in terms of the number of publications on facial paralysis rehabilitation and physiotherapy research. Seeing from another angle, the journals that focus on otolaryngology published the most number of articles in rehabilitation and physiotherapy studies, whereas most acupuncture studies on facial paralysis were published in the alternative and complementary medicine joumals. CONCLUSION： Study of facial paralysis remains an area of active investigation and innovation. Further clinical studies in humans addressing the use of growth factors or stem cells continue to successful facial nerve regeneration.

Visualization analysis of research frontiers and trends in nerve regeneration and osseoperception in the repair of tooth loss

This study analyzed 85 articles indexed by the Web of Science concerning nerve regeneration and osseoperception during tooth loss repair. Using the Web of Science database and Citespace Ⅲ software, a document co-citation network map was drawn by document co-citation analysis and word frequency analysis methods. Combined with emergent node secondary literature retrieval, subject headings with apparent changing word frequency trends were retrieved so as to identify research frontiers and development trends. Research frontiers and hotspots for neuronal calcium sensor protein were quantitatively explored to forecast future research developments in nerve regeneration and osseoperception during repair of tooth loss.

A MXene-Based Bionic Cascaded-Enzyme Nanoreactor for Tumor Phototherapy/Enzyme Dynamic Therapy and Hypoxia-Activated Chemotherapy

The enzyme-mediated elevation of reactive oxygen species(ROS)at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment.Herein,we proposed a camouflaged bionic cascaded-enzyme nanoreactor based on Ti_(3)C_(2)nanosheets for combined tumor enzyme dynamic therapy(EDT),phototherapy and deoxygenation-activated chemotherapy.Briefly,glucose oxidase(GOX)and chloroperoxidase(CPO)were chemically conjugated onto Ti_(3)C_(2)nanosheets,where the deoxygenation-activated drug tirapazamine(TPZ)was also loaded,and the Ti_(3)C_(2)-GOX-CPO/TPZ(TGCT)was embedded into nanosized cancer cell-derived membrane vesicles with high-expressed CD47(m_eTGCT).Due to biomimetic membrane camouflage and CD47 overexpression,m_eTGCT exhibited superior immune escape and homologous targeting capacities,which could effectively enhance the tumor preferential targeting and internalization.Once internalized into tumor cells,the cascade reaction of GOX and CPO could generate HClO for efficient EDT.Simultaneously,additional laser irradiation could accelerate the enzymic-catalytic reaction rate and increase the generation of singlet oxygen(~1O_(2)).Furthermore,local hypoxia environment with the oxygen depletion by EDT would activate deoxygenation-sensitive prodrug for additional chemotherapy.Consequently,m_eTGCT exhibits amplified synergistic therapeutic effects of tumor phototherapy,EDT and chemotherapy for efficient tumor inhibition.This intelligent cascaded-enzyme nanoreactor provides a promising approach to achieve concurrent and significant antitumor therapy.

A Survey on Heliumspeech Communications in Saturation Diving

With the development of society and the progress of technology,more and more ocean activities are carried out.It results in booming of deep-sea diving.The use of helium-oxygen mixture(as a kind of breathing gas)solves the physiological problems of divers in saturated diving,but it brings about the Heliumspeech voice communication problem,the drop of speech intelligibility.There is no doubt that the effective speech communication must be provided for supporting the life and work of divers in deep-sea.This paper describes the mechanism of forming heliumspeech,discusses the effects of pressure and helium environment on the speech spectrum,compares the pros and cons of the time-domain and frequency-domain unscrambling techniques,shows the challenges in heliumspeech communications.Finally,it briefly introduces the deep learning,and points out that deep learning/machine learning may be a perfectly unscrambling technique.

Joint Beamforming and Time Switching Designs for Energy-Constrained Cognitive Two-Way Relay Networks

In this paper, we investigate a joint beamforming and time switching(TS) design for an energy-constrained cognitive two-way relay(TWR) network. In the network, the energy-constrained secondary user(SU) relay employs TS protocol to harvest energy from the signals sent by the circuit-powered primary user(PU) transmitter, and then exploits the harvested energy to perform information forwarding. Our aim is to maximize the sum rate of SUs under the constraints of the data rate of PU, the energy harvesting and the transmit power of the SU relay. To determine the beamforming matrix and TS ratio, we decouple the original non-convex problem into two subproblems which can be solved by semidefinite relaxation and successive convex optimization methods. Furthermore, we derive closed form expressions of the optimal solutions for each subproblem, which facilitates the design of a suboptimal iterative algorithm to handle the original sum rate maximization problem. Simulation results are presented to illustrate the effectiveness and superior performance of the proposed joint design against other conventional schemes in the literature.

Fuzzy Service Aware Adaptive Cooperative Spectrum Sensing Algorithm

Based on the service characteristics and the sensing ability for secondary users, a joint optimization scheme of spectrum detection and allocation is investigated to expand the available sensing region and allocate the Qo S-specified channels. On the aspect of spectrum detection, due to the available detection index with the global detection metrics, cooperation thresholds are adaptively adjusted to select the cooperative model for maximizing the available sensing region. On the aspect of spectrum allocation, for different service category, the idle channels are efficiently allocated that depend on their stability and available bandwidth. Meanwhile, based on the requested rates defined by fuzzy theory, the secondary users can be divided into two categories, i.e.,delay sensitive service and reliability sensitive service. Finally, the Qo S-specified channels from the targeted spectrum subset are allocated to secondary users. Simulation results show that our proposed algorithm can not only expand the available sensing region,but also decrease the outage probability of delay sensitive services. Additionally, it enables stable power consumption in the time-variation channel.

A novel two-dimensional nanoheterojunction via facilitating electron–hole pairs separation for synergistic tumor phototherapy and immunotherapy

Nanomaterial-mediated phototherapy in tumor treatment has been developed rapidly in the past few years due to its noninvasive character.However,the low energy conversion efficiency and high recombination rate of the photo-triggered electron–hole pairs of single nano-agent limit the phototherapy efficiency.Herein,we constructed a novel two-dimensional nanoheterojunction MoS_(2)-Ti_(3)C_(2)(MT),which allowed a high photothermal conversion efficiency(59.1%)as well as an effective separation of photo-triggered electron–hole pairs for reactive oxygen species(ROS)generation under single 808 nm laser irradiation.Upon the modification of the mitochondrial targeted molecule(3-proxycarboxylic)triphenyl phosphine bromide(TPP)and 4T1 cell membrane,m@MoS_(2)-Ti_(3)C_(2)/TPP(m@MTT)could effectively target to the tumor cell and further locate to the mitochondria to amplify tumor-specific oxidative stress,which not merely effectively inhibits the local tumor growth but also induces tumor immunogenic cell death(ICD)for activating antitumor immune response.Additionally,cytosine guanine dinucleotide(CPG),as a Toll-like receptor 9(TLR9)agonist,was further introduced to the system to boost adaptive immune responses,resulting in improved level of cytotoxic T cells as well as a decrease in the number of regulatory T cells.In vivo antitumor mechanism studies demonstrated that not only the primary and distant tumors in 4T1 bearing-tumor mice model were significantly inhibited,but also the lung metastasis of tumor was effectively suppressed.Therefore,this work revealed the ROS generation mechanism of MT nanoheterojunction and provided a novel strategy to fabricate a biomedically applicable MT nanoheterojunction for tumor treatment.

A targeting black phosphorus nanoparticle based immune cells nanoregulator for photodynamic/photothermal and photo-immunotherapy

Photo-immunotherapy is a novel therapeutic approach against malignant tumors with minimal invasiveness.Herein,a targeting multifunctional black phosphorus(BP)nanoparticle,modified by PEGylated hyaluronic acid(HA),was designed for photothermal/photodynamic/photo-immunotherapy.In vitro and in vivo assays indicated that HA-BP nanoparticles possess excellent biocompatibility,stability,and sufficient therapeutic efficacy in the combined therapy of photothermal therapy(PTT)and photodynamic therapy(PDT)for cancer therapy.Moreover,the results of in vitro showed that HA-BP down-regulated the expression of CD206(M2 macrophage marker)by 42.3%and up-regulated the ratio of CD86(M1 macrophage marker)by 59.6%,indicating that HABP nanoparticles have functions in remodeling tumor associated macrophages(TAMs)phenotype(from protumor M2 TAMs to anti-tumor M1 macrophages).Fluorescence(FL)and photoacoustic(PA)multimodal imaging confirmed the selective accumulation of HA-BP in tumor site via both CD44^+mediated active targeting and passive EPR effect.In vitro and in vivo studies suggested that the combined therapy of PDT,PTT and immunotherapy using HA-BP could not only significantly inhibit original tumor but also induce immunogenic cell death(ICD)and release Damage-associated molecular patterns(DAMPs),which could induce maturation of dendritic cells(DCs)and activate effector cells that robustly evoke the antitumor immune responses for cancer treatment.This study expands the biomedical application of BP nanoparticles and displays the potential of modified BP as a multifunctional therapeutic platform for the future cancer therapy.

SciFinder-guided rational design of fluorescent carbon dots for ratiometric monitoring intracellular pH fluctuations under heat shock

Intracellular pH plays a significant role in various biological processes, including cell proliferation,apoptosis, metabolism, enzyme activity and homeostasis. In this work, a novel design strategy for the preparation of pH responsive carbon dots(CDs-pH) for ratiometric intracellular imaging was reported. By using SciFinder database, fluorescent CDs-pH with the required p Kavalue of 6.84 were rationally designed, which is vital important for precise sensing of intracellular pH. As a result, the synthesized CDspH demonstrated robust ability to test pH fluctuations within the physiological range of 5.4-7.4. The CDspH was further utilized for fluorescent ratiometric imaging of pH in living HeLa cells, effectively avoided the influence of autofluorescence from native cellular species. Moreover, real-time monitoring of intracellular pH fluctuation under heat shock was successfully realized. This SciFinder-guided design strategy is simple and flexible, which has a great potential to be used for the development of other types of CDs for various applications.

Multiple stimuli-responsive nanosystem for potent,ROS-amplifying,chemo-sonodynamic antitumor therapy

Although sonodynamic therapy(SDT)is a promising non-invasive tumor treatment strategy due to its safety,tissue penetration depth and low cost,the hypoxic tumor microenvironment limits its therapeutic effects.Herein,we have designed and developed an oxygen-independent,ROS-amplifying chemo-sonodynamic antitumor therapy based on novel pH/GSH/ROS triple-responsive PEG-PPMDT nanoparticles.The formulated artemether(ART)/Fe_(3)O_(4)-loaded PEG-PPMDT NPs can rapidly release drug under the synergistic effect of acidic endoplasmic pH and high intracellular GSH/ROS levels to inhibit cancer cell growth.Besides,the ROS level in the NPs-treated tumor cells is magnified by ART via interactions with both Fe^(2+)ions formed in situ at acidic pH and external ultrasound irradiation,which is not affected by hypoxia tumor microenvironment.Consequently,the enriched intracellular ROS level can cause direct necrosis of ROS-stressed tumor cells and further accelerate the drug release from the ROS-responsive PEG-PPMDT NPs,achieving an incredible antitumor potency.Specifically,upon the chemo-sonodynamic therapy by ART/Fe_(3)O_(4)-loaded PEG-PPMDT NPs,all xenotransplants of human hepatocellular carcinoma(HepG2)in nude mice shrank significantly,and 40% of the tumors were completely eliminated.Importantly,the Fe3O4 encapsulated in the NPs is an efficient MRI contrast agent and can be used to guide the therapeutic procedures.Further,biosafety analyses show that the PEG-PPMDT NPs possess minimal toxicity to main organs.Thus,our combined chemo-sonodynamic therapeutic method is promising for potent antitumor treatment by controlled release of drug and facile exogenous generation of abundant ROS at target tumor sites.