Using nanotechnology for improving the immunotherapy efficiency represents a major research interest in recent years. However, there are paradoxes and obstacles in using a single nanoparticle to ...fulfill all the requirements in the complicated immune activation processes. Herein, a supramolecular assembled programmable immune activation nanomedicine (PIAN) for sequentially finishing multiple steps after intravenous injection and eliciting robust antitumor immunity in situ is reported. The programmable nanomedicine is constructed by supramolecular assembly via host–guest interactions between poly‐(N‐2‐hydroxyethyl)‐aspartamide‐Pt(IV)/β‐cyclodextrin (PPCD), CpG/polyamidoamine‐thioketal‐adamantane (CpG/PAMAM‐TK‐Ad), and methoxy poly(ethylene glycol)‐thioketal‐adamantane (mPEG‐TK‐Ad). After intravenous injection and accumulation at the tumor site, the high level of reactive oxygen species in the tumor microenvironment promotes PIAN dissociation and the release of PPCD (mediating tumor cell killing and antigen release) and CpG/PAMAM (mediating antigen capturing and transferring to the tumor‐draining lymph nodes). This results in antigen‐presenting cell activation, antigen presentation, and robust antitumor immune responses. In combination with anti‐PD‐L1 antibody, the PIAN cures 40% of mice in a colorectal cancer model. This PIAN provides a new framework for designing programmable nanomedicine as in situ cancer vaccine for cancer immunotherapy.
A novel strategy to use programmable nanomedicine for cancer immunotherapy is presented. A programmable immune activation nanomedicine (PIAN) is constructed through supramolecular modular assembly, which automatically transforms after intravenous injection and finishes sequential multiple steps for eliciting robust immune responses in vivo.
Using nanotechnology for cancer vaccine design holds great promise because of the intrinsic feature of nanoparticles in being captured by antigen-presenting cells (APCs). However, there are still ...obstacles in current nanovaccine systems in achieving efficient tumor therapeutic effects, which could partially be attributed to the unsatisfactory vaccine carrier design. Herein, we report a mannan-decorated pathogen-like polymeric nanoparticle as a protein vaccine carrier for eliciting robust anticancer immunity. This nanovaccine was constructed as a core-shell structure with mannan as the shell, polylactic acid-polyethylenimine (PLA-PEI) assembled nanoparticle as the core, and protein antigens and Toll-like receptor 9 (TLR9) agonist CpG absorbed onto the PLA-PEI core via electrostatic interactions. Compared to other hydrophilic materials, mannan decoration could greatly enhance the lymph node draining ability of the nanovaccine and promote the capturing by the CD8+ dendritic cells (DCs) in the lymph node, while PLA-PEI as the inner core could enhance antigen endosome escape thus promoting the antigen cross-presentation. In addition, mannan itself as a TLR4 agonist could synergize with CpG for maximally activating the DCs. Excitingly, we observed in several murine tumor models that using this nanovaccine alone could elicit robust immune response in vivo and result in superior anti-tumor effects with 50% of mice completely cured. This study strongly evidenced that mannan decoration and a rationally designed nanovaccine system could be quite robust in tumor vaccine therapy.
Reconstruction of bone defects, especially the critical-sized defects, with mechanical integrity to the skeleton is important for a patient's rehabilitation, however, it still remains challenge. ...Utilizing biomaterials of human origin bone tissue for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural bone tissue with regard to its properties. However, not only efficacious and safe but also cost-effective and convenient are important for regenerative biomaterials to achieve clinical translation and commercial success. Advances in our understanding of regenerative biomaterials and their roles in new bone formation potentially opened a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multicomponent construction of native extracellular matrix (ECM) for cell accommodation, the ECM-mimicking biomaterials and the naturally decellularized ECM scaffolds were used to create new tissues for bone restoration. On the other hand, with the going deep in understanding of mesenchymal stem cells (MSCs), they have shown great promise to jumpstart and facilitate bone healing even in diseased microenvironments with pharmacology-based endogenous MSCs rescue/mobilization, systemic/local infusion of MSCs for cytotherapy, biomaterials-based approaches, cell-sheets/-aggregates technology and usage of subcellular vesicles of MSCs to achieve scaffolds-free or cell-free delivery system, all of them have been shown can improve MSCs-mediated regeneration in preclinical studies and several clinical trials. Here, following an overview discussed autogenous/allogenic and ECM-based bone biomaterials for reconstructive surgery and applications of MSCs-mediated bone healing and tissue engineering to further offer principles and effective strategies to optimize MSCs-based bone regeneration.
•Focusing on MSCs based bone regeneration.•Discussed cytotherapy, cell-free therapies and cell-aggregates technology in detail.•Stating the approaches of MSCs in diseased microenvironments.
Objective
The aim is to evaluate the global, regional, and national trends in the burden of children and adolescents under 14 from 1990 to 2019, as well as future trend predictions.
Methods
In Global ...Burden of Disease (GBD), we reported the incidence, prevalence rate and the years lived with disability (YLDs), the incidence per 100,000 people, and the average annual percentage change (AAPC). We further analyzed these global trends by age, gender, and social development index (SDI). We use joinpoint regression analysis to determine the year with the largest global trend change. Bayesian age-period-cohort (BAPC) was used for predictions.
Results
From 1990 to 2019, the incidence rate, prevalence and YLDs of AD under 14 years old showed a downward trend. The incidence rate of AD among people under 5 years old has the largest decline AAPC: -0.13 (95% CI: -0.15 to -0.11),
P
< 0.001. The incidence rate, prevalence and YLDs of AD in women were higher than those in men regardless of age group. Regional, Asia has the highest AD incidence rate in 2019. National, Mongolia has the highest AD incidence rate in 2019. The largest drop in AD incidence rate, prevalence and YLDs between 1990 and 2019 was in the United States.
Conclusion
From 1990 to 2019, the global incidence rate of children and adolescents under 14 declined. With the emergence of therapeutic drugs, the prevalence and YLDs rate declined significantly. From 2020 to 2030, there is still a downward trend.
Ion channels modulate the flow of ions into and out of a cell or intracellular organelle, leading to generation of electrical or chemical signals and regulating ion homeostasis. The abundance of ion ...channels in the plasma and intracellular membranes are subject to physiological and pathological regulations. Abnormal and dysregulated expressions of many ion channels are found to be linked to cancer and cancer chemo-resistance. Here, we will summarize ion channels distribution in multiple tumors. And the involvement of ion channels in cancer chemo-resistance will be highlighted.
There are some problems that the bit error rate is high but generation rate is low in existing physical layer secret key generation schemes, so we propose a highly consistent and high-speed secret ...key generation scheme in this paper. This scheme not only can achieve high consistency and high generation rate, but also can ensure randomness of secret key. First, the scheme conducts channel pre-detection to calculate weighted vectors to smooth the noise. Then, a modified level crossing algorithm is proposed to improve key consistency greatly. Furthermore, we put forward cyclic interleaving quantization method that can linearly improve key generation rate and enhance randomness of secret key. Simulation results show that the scheme can achieve zero bit disagreement, and key generation rate can reach at least 495% when SNR is 20 dB.
An "exosome" is a nanoscale membrane vesicle derived from cell endocytosis that functions as an important intercellular communication mediator regulating the exchange of proteins and genetic ...materials between donor and surrounding cells. Exosomes secreted by normal and cancer cells participate in tumor initiation, progression, invasion, and metastasis. Furthermore, immune cells and cancer cells exert a two-way bidirectional regulatory effect on tumor immunity by exchanging exosomes. Current studies on exosomes have further expanded their known functions in physiological and pathological processes. The purpose of this review is to describe their discovery and biological functions in the context of their enormous potential in the clinical diagnosis, prevention, and treatment of cancer as well as bacterial and viral infectious diseases.
The public health issue of glucolipid metabolic disorders (GLMD) has grown significantly, posing a grave threat to human wellness. Its prevalence is rising yearly and tends to affect younger people. ...Metaflammation is an important mechanism regulating body metabolism. Through a complicated multi-organ crosstalk network involving numerous signaling pathways such as NLRP3/caspase-1/IL-1, NF-B, p38 MAPK, IL-6/STAT3, and PI3K/AKT, it influences systemic metabolic regulation. Numerous inflammatory mediators are essential for preserving metabolic balance, but more research is needed to determine how they contribute to the co-morbidities of numerous metabolic diseases. Whether controlling the inflammatory response can influence the progression of GLMD determines the therapeutic strategy for such diseases. This review thoroughly examines the role of metaflammation in GLMD and combs the research progress of related therapeutic approaches, including inflammatory factor-targeting drugs, traditional Chinese medicine (TCM), and exercise therapy. Multiple metabolic diseases, including diabetes, non-alcoholic fatty liver disease (NAFLD), cardiovascular disease, and others, respond therapeutically to anti-inflammatory therapy on the whole. Moreover, we emphasize the value and open question of anti-inflammatory-based means for treating GLMD.
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•Metaflammation has a crucial role in regulating Glucolipid metabolic disorders (GLMD).•Inflammation-associated signaling pathways influence the development of multiple metabolic diseases.•The role of inflammatory mediators in the co-morbidity of multiple metabolic diseases needs to be further investigated.•Anti-inflammatory treatment shows an overall therapeutic effect on multiple metabolic diseases simultaneously.
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