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Undoubtedly, the sensory organs of biological systems have been evolved to accurately detect and locate the external stimuli, even if they are very weak. However, the mechanism underlying this ability is still not fully understood. Previously, it had been shown that stochastic resonance may be a good candidate to explain this ability, by which the response of a system to an external signal is amplified by the presence of noise. Recently, it is pointed out that the initial phase diversity in external signals can be also served as a simple and feasible mechanism for weak signal detection or amplification in excitable neurons. We here make a brief review on this progress. We will show that there are two kinds of effects of initial phase diversity: one is the phase disorder, i.e., the initial phases are different and static, and the other is the phase noise, i.e., the initial phases are time-varying like noise. Both cases show that initial phase diversity in subthreshold periodic signals can indeed play a constructive role in the emergence of sustained spiking activity. As initial phase diversity can mimic different arrival times from source signal to sensory organs, these findings may provide a cue for understanding the hunting behaviors of some biological systems.

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In recent years, exploring the physical mechanisms of brain functions has been a hot topic in the fields of nonlinear dynamics and complex networks, and many important achievements have been made, mainly based on the characteristic features of time series of human brain. To speed up the further study of this problem, herein we make a brief review on these important achievements, which includes the aspects of explaining: (i) the mechanism of brain rhythms by network synchronization, (ii) the mechanism of unihemispheric sleep by chimera states, (iii) the fundamental difference between the structural and functional brain networks by remote synchronization, (iv) the mechanism of stronger detection ability of human brain to weak signals by remote firing propagation, and (v) the mechanism of dementia patterns by eigen‐microstate analysis. As a brief review, we will mainly focus on the aspects of basic ideas, research histories, and key results but ignore the tedious mathematical derivations. Moreover, some outlooks will be discussed for future studies.

The development of cancer vaccines is at the forefront of cancer immunotherapy. Most existing strategies to induce an efficient anti‐tumor immune response rely on molecular adjuvants and the incorporation of complex synthetic vectors into vaccine formulations. In contrast, this study introduces a one‐step engineering technique to assemble the model antigen, Ovalbumin (OVA), into amyloid aggregates, leveraging biomimetic folding and aggregation to create non‐fibrillar OVA globular aggregates and OVA amyloid‐like fibrils as single‐component, adjuvant‐free vaccines. Notably, the OVA amyloid‐like fibrils induced stronger immune responses compared to the native form, as evidenced by robust humoral immune reactions and the establishment of immune memory. These enhanced responses can be attributed to the self‐adjuvant effect of the unique assembled structure, which preserves antigenic epitopes, improves antigen stability, facilitates antigen internalization, prolongs retention at the injection site, enhances antigen trafficking to the lymphoid organs, and promotes increased secretion of antibodies and cytokines. Furthermore, the efficacy of the vaccine was validated in a high OVA‐expressing tumor model, demonstrating the potential of OVA amyloid‐like fibrils as an effective vaccine for cancer immunoprevention. This minimalist self‐adjuvant vaccine strategy holds promising implications for cancer immunotherapy and can inform the design of other protein antigen‐based vaccines. A one‐step engineering method assembles the model antigen OVA into amyloid‐like fibrils, forming a single‐component, adjuvant‐free vaccine. The OVA fibrils effectively enhance immune responses and induce antigen‐specific memory, showing promise as a cancer vaccine. This streamlined, carrier‐free approach opens new avenues for designing protein antigen‐based vaccines.

Tumor vaccine therapy, which can induce tumor antigen-specific cellular immune responses to directly kill tumor cells, is considered to be one of the most promising tumor immunotherapies. How to elicit effective tumor antigen-specific cellular immunity is the key for the development of tumor vaccines. However, current tumor vaccines with conventional antigen delivery systems mainly induce humoral immunity but not effective cellular immunity. In this study, based on pH-sensitive, ordered macro-microporous zeolitic imidazolate framework-8 (SOM-ZIF-8) and hexadecylsulfonylfluoride (HDSF), an intelligent tumor vaccine delivery system SOM-ZIF-8/HDSF was developed to elicit potent cellular immunity. Results demonstrated that the SOM-ZIF-8 particles could efficiently encapsulate antigen into the macropores, promote antigen uptake by antigen-presenting cells, facilitate lysosomal escape, and enhance antigen cross-presentation and cellular immunity. In addition, the introduction of HDSF could up-regulate the lysosomal pH to protect antigens from acid degradation, which further promoted antigen cross-presentation and cellular immunity. The immunization tests showed that the tumor vaccines based on the delivery system improved antigen-specific cellular immune response. Moreover, the tumor vaccines significantly inhibited tumor growth in B16 melanoma-bearing C57BL/6 mice. These results indicate that SOM-ZIF-8/HDSF as an intelligent vaccine delivery system could be used for the development of novel tumor vaccines.

Southern corn rust (SCR) is a destructive maize disease caused by Puccinia polysoraUnderw. To investigate the mechanism of SCR resistance in maize, a highly resistant inbred line, L119A, and a highly susceptible line, Lx9801, were subjected to gene mapping and transcriptome analysis. Bulked-segregant analysis coupled with whole-genome sequencing revealed several quantitative trait loci (QTL) on chromosomes 1, 6, 8, and 10. A set of 25 genes, including two coiled-coil nucleotide-binding site leucine-rich repeat (CC-NBS-LRR) genes, were identified as candidate genes for a major-effect QTL on chromosome 10. To investigate the mechanism of SCR resistance in L119A, RNA-seq of P. polysora-inoculated and non-inoculated plants of L119A and Lx9801 was performed. Unexpectedly, the number of differentially expressed genes in inoculated versus non-inoculated L119A plants was about 10 times that of Lx9801, with only 29 common genes identified in both lines, suggesting extensive gene expression changes in the highly resistant but not in the susceptible line. Based on the transcriptome analysis, one of the CC-NBS-LRR candidate genes was confirmed to be upregulated in L119A relative to Lx9801 independently of P. polysorainoculation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that transcription factors, as well as genes involved in defense responses and metabolic processes, were dominantly enriched, with the phenylpropanoid biosynthesis pathway most specifically activated. Consistently, accumulation of phenylpropanoid-derived lignin, especially S lignin, was drastically increased in L119A after P. polysorainoculation, but remained unchanged in Lx9801, suggesting a critical role of lignin in SCR resistance. A regulatory network of defense activation and metabolic change in SCR-resistant maize upon P. polysorainfection is described.

Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes1,2. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized3–6. Here we define a critical role of IL-27–IL-27Rα signalling in improving thermogenesis, protecting against diet-induced obesity and ameliorating insulin resistance. Mechanistic studies demonstrate that IL-27 directly targets adipocytes, activating p38 MAPK–PGC-1α signalling and stimulating the production of UCP1. Notably, therapeutic administration of IL-27 ameliorated metabolic morbidities in well-established mouse models of obesity. Consistently, individuals with obesity show significantly decreased levels of serum IL-27, which can be restored after bariatric surgery. Collectively, these findings show that IL-27 has an important role in orchestrating metabolic programs, and is a highly promising target for anti-obesity immunotherapy.

Digital holography is a useful tool to image microscopic particles. Reconstructed holograms give high-resolution shape information that can be used to identify the types of particles. However, the process of reconstructing holograms is computationally intensive and cannot easily keep up with the rate of data acquisition on low-power sensor platforms. In this work, we explore the possibility of performing object clustering on holograms that have not been reconstructed, i.e., images of raw interference patterns, using the latent representations of a deep-learning autoencoder and a self-organizing mapping network in a fully unsupervised manner. We demonstrate this concept on synthetically generated holograms of different shapes, where clustering of raw holograms achieves an accuracy of 94.4%. This is comparable to the 97.4% accuracy achieved using the reconstructed holograms of the same targets. Directly clustering raw holograms takes less than 0.1 s per image using a low-power CPU board. This represents a three-order of magnitude reduction in processing time compared to clustering of reconstructed holograms and makes it possible to interpret targets in real time on low-power sensor platforms. Experiments on real holograms demonstrate significant gains in clustering accuracy through the use of synthetic holograms to train models. Clustering accuracy increased from 47.1% when the models were trained only on the real raw holograms, to 64.1% when the models were entirely trained on the synthetic raw holograms, and further increased to 75.9% when models were trained on the both synthetic and real datasets using transfer learning. These results are broadly comparable to those achieved when reconstructed holograms are used, where the highest accuracy of 70% achieved when clustering raw holograms outperforms the highest accuracy achieved when clustering reconstructed holograms by a significant margin for our datasets.

A noncontact method to identify sparsely distributed plastic pellets is proposed by integrating holography and Raman spectroscopy in this study. Polystyrene and poly(methyl methacrylate) resin pellets with a size of 3 mm located in a 20 cm water channel were illuminated using a collimated continuous wave laser beam with a diameter of 4 mm and wavelength of 785 nm. The same laser beam was used to take a holographic image and Raman spectrum of a pellet to identify the shape, size, and composition of material. Using the compact system, the morphological and chemical analysis of pellets in a large volume of water was performed. The reported method demonstrates the potential for noncontact continuous in situ monitoring of microplastics in water without collection and separation.

In past decades, a lot of studies have been carried out on complex networks and heat conduction in regular lattices. However, very little attention has been paid to the heat conduction in complex networks. In this work, we study (both thermal and electric) energy transport in physical networks rewired from 2D regular lattices. It is found that the network can be transferred from a good conductor to a poor conductor, depending on the rewired network structure and coupling scheme. Two interesting phenomena were discovered: (i) the thermal-siphon effect—namely the heat flux can go from a low-temperature node to a higher-temperature node and (ii) there exits an optimal network structure that displays small thermal conductance and large electrical conductance. These discoveries reveal that network-structured materials have great potential in applications in thermal-energy management and thermal-electric-energy conversion.

In clinical diagnosis, accurate and reliable measurement technologies for the detection of disease biomarkers at ultralow concentrations can provide guidance for the initiation of treatment and potentially improve survival for patients. Here, we demonstrate an optical microfiber reader for enhanced analytical sensitivity in enzyme-linked immunosorbent assays (ELISA) that enables the detection of tiny changes of the refractive index (RI) induced by the catalyzed oxidation of substrate, owing to the strong interaction between the evanescent field and surrounding medium. By employing the microfiber reader for the C-reaction protein (CRP) and interleukin-6 (IL-6) assays after the enzymatic signal amplification in ELISA, we experimentally investigate the biosensing capacity of the device. As a result, log–linear relations of CRP and IL-6 detection in PBS and human serum between the concentration and spectral response were obtained at both nanogram and picogram levels, respectively, and anti-CRP/HRP detection as low as 9.75 pg/mL was achieved, which was undetectable by the conventional spectrophotometry. With a stable, accurate, and color-free detection capacity, this optical microfiber reader has a promising prospect in early disease diagnosis and clinical treatment.

In immunotherapy, induction of potent cellular immunity by vaccination is essential to treat intracellular infectious diseases and tumors. In this work, we designed a new synthetic peptide carrier, Cys-Trp-Trp-Arg8-Cys-Arg8-Cys-Arg8-Cys, for vaccine delivery by integrating a redox-responsive disulfide bond cross-linking and cell-penetrating peptide arginine octamer. The carrier peptide bound to the antigen protein ovalbumin (OVA) via electrostatic self-assembly to form peptide/OVA nanocomposites. Then, the spontaneous oxidization of the thiols of the cysteine residues induced interpeptide disulfide bond cross-linking to construct denser peptide/OVA condensates. The cell-penetrating peptides incorporated in the carrier peptide could increase antigen uptake by antigen presenting cells. After being internalized by antigen presenting cells, the antigen could be rapidly released in cytoplasm along with degradation of the disulfide bonds by intracellular glutathione, which could promote potent CD8+T cell immunity. The cross-linked peptide/OVA condensates were used for subcutaneous vaccination. The results showed that the peptide carrier mediated potent antigen-specific immune response by significantly increasing IgG titer; splenocyte proliferation; the secretion level of cytokines INF-γ, IL-12, IL-4, and IL-10; immune memory function, and the activation and maturation of dendritic cells. From the results, the low-molecular weight vaccine-condensing peptide with definite chemical composition could be developed as a novel class of vaccine delivery systems.

Biosafety and the targeting ability of gene delivery systems are critical aspects for gene therapy of cancer. In this study, we report the synthesis and use of redox-responsive poly(amido amine) (PAA) with good biocompatibility and biodegradation as a gene carrier material. A tumor-specific tissue penetration peptide, internalizing-RGD (iRGD) was then conjugated to PAA with an amidation reaction. In experiments using H1299 cells, PAA-iRGD was found to have a lower cytotoxicity and higher cellular uptake efficiency compared to PAA. An siRNA, specific to epidermal growth factor receptor (EGFR) that is overexpressed on the lung cancer cell surface and often targeted in lung cancer treatment, was designed to silence EGFR (i.e., siEGFR) for delivery by the gene carrier PAA-iRGD. EGFRgene silencing, apoptosis, antiproliferation, and antitumor effects of PAA-iRGD/siEGFR were evaluated in vitroand in vivo. PAA-iRGD/siEGFR displayed a much higher gene silencing ability compared to PAA and polyethylenimine (25 kDa), significantly inhibited the proliferation and migration of H1299 cells, and elicited significant cell apoptosis. Moreover, intravenously injected PAA-iRGD/siEGFR inhibited lung tumor growth in vivo. These results suggest that PAA-iRGD with good biocompatibility, biodegradation, and targeting ability could be a promising gene delivery system for gene therapy of cancers.

In the treatment of cancers, molybdenum disulfide (MoS2) has shown great potential as a photo absorbing agent in photothermal therapy and meanwhile as an anti-tumor drug delivery system in chemotherapy. However, the poor dispersibility and stability of MoS2 in aqueous solutions limit its applications in cancer therapy. To overcome the shortcomings, MoS2 was modified mainly by surface adsorption of linear polymers, such as chitosan and polyethylene glycol. As reported, the linear polymers could be more rapidly cleared from blood circulation than their branched counterparts. Herein, we developed hyperbranched polyglycidyl (HPG)-modified MoS2 (MoS2-HPG) by absorbing HPG on the MoS2 surface. The MoS2-HPG as a novel photo absorbing agent was also used as a nano-scaled carrier to load anti-tumor drug doxorubicin hydrochloride (DOX) (MoS2-HPG-DOX) for combined chemo-photothermal therapy. The physicochemical and photothermal properties of MoS2-HPG were measured, and the results indicate that MoS2-HPG had good dispersion and stability in aqueous solutions, and also high photothermal conversion efficiency. MoS2-HPG displayed good biocompatibility in hemocompatibility and cytotoxicity evaluations in vitro. Furthermore, the combined chemo-photothermal therapy by using MoS2-HPG-DOX demonstrated better anti-cancer effect than the individual chemotherapy or photothermal therapy alone. From the results, MoS2-HPG with combined chemo-photothermal therapy could be developed as a promising therapeutic formulation for clinical cancer treatment.

Fluorescent carbon dots (CDs) as a luminescent nanomaterial have obtained much attention in the biomedical field. To make good use of their luminescent property and nanoscaled size, we developed CDs as a vaccine delivery system for intranasal immunization in this work. To this aim, polyethylenimine-modified CDs were prepared via a simple microwave method. Intranasal immunization was performed by using the CDs as an antigen carrier to deliver model protein antigen ovalbumin. The results showed that the CDs as an intranasal vaccine delivery system enhanced the immunization efficacy by significantly increasing IgG titer, IgA induction in the local and distant mucous membrane sites, splenocyte proliferation, cytokine IFN-γ secretion by splenocytes, and memory T cells. From the results, the CDs could be used as vaccine delivery systems with the advantage of tracing the antigen transportation from administration site to the lymph organs.

Polycations such as polyethylenimine and chitosan have been widely used as mucosal vaccine delivery systems due to their permeation enhancement effect. Preferably, environmentally responding biodegradable polycations would be better carrier materials for mucosal vaccine delivery. Disulfide bond-based redox-sensitive polycations could respond to the higher intracellular glutathione concentration and degrade in the cytoplasm via the breakage of the disulfide bonds, which are particularly suitable for antigen delivery. In this work, we evaluated the potential of redox-sensitive, biodegradable polycation poly(amido amine) (PAA) as mucosal vaccine carriers. From the primary studies with ovalbumin used as a model protein antigen, it is found that PAA could complex with and encapsulate protein antigen via electrostatic attraction, enhance the cellular uptake of antigen by dendritic cell line DC2.4, prolong antigen residence in nasal cavity, and promote antigen permeation into nasal submucosal layer. Further, Balb/c mice were intranasally immunized with PAA-delivered recombinant hemagglutinin (HA) antigen protein of H7N9 influenza virus. The PAA/HA formulations induced significantly more potent systemic IgG response and mucosal IgA response, higher splenocyte proliferation activity, higher secretion levels of cytokines IFN-γ and IL-4 by splenocytes, more memory CD4+and CD8+T cells, and more DCs expressing MHC II molecule. From the results, the redox-responsive polycation PAA as vaccine carriers helped elicit more potent cellular and humoral immune responses. Particularly, PAA induced much higher cellular immune response compared with previously reported carrier materials. The intelligent PAA could be developed as efficient mucosal vaccine delivery systems for clinical applications.

As a potential method for tumor treatment, tumor vaccine immunization induces a tumor-specific cellular immune response via immunization with tumor antigens. The delivery of exogenous antigen proteins into the cytoplasm of antigen-presenting cells is well known to induce an intensive cellular immune response for tumor treatment. In this work, we fluorinated a redox-responsive hyperbranched poly(amidoamine) (HPAA) with heptafluorobutyric anhydride to prepare a fluorinated HPAA (HPAA-F7) for use as a vaccine delivery system for antitumor therapy. The immunization results show that HPAA-F7 as a vaccine carrier could effectively promote the intracellular uptake and cytoplasmatic delivery of antigen proteins and induce potent antitumor cellular immunity. The novel vaccine carrier HPAA-F7 could be further developed for antitumor immunotherapy.

Utilizing nanoparticles to deliver subunit vaccines can be viewed as a promising strategy for enhancing the immune response, especially with regard to cellular immunity to fight against infectious viruses and malignant cancer. Nevertheless, its applications are still far from practicality because of some limitations such as high cost, non-biocompatibility, non-biodegradability, and the inefficient stimulation of cytotoxic T lymphocyte (CTL) response. In this study, we use metal–organic framework (MOF) MIL-101-Fe-NH2nanoparticles as carriers to fabricate an innovative reduction-responsive antigen delivery system for cotransporting the antigen model ovalbumin (OVA) and an immune adjuvant, unmethylated cytosine–phosphate–guanine (CpG) oligonucleotide. In vitro cellular tests show that the MOF nanoparticles can not only greatly improve the uptake of OVA by the antigen-presenting cells but also smartly deliver both OVA and CpG into the same cell. By feat of the reductively controllable release of OVA and the promoting function of CpG, the delivery system can elicit strong cellular immunity and CTL response in mice. Moreover, the increased frequencies of effector memory T cells inspired by the delivery system indicate that it can induce a potent immune memory response. These results demonstrate that MOF nanoparticles are excellent vehicles for codelivering antigen and immune adjuvant and may find wider applications in biomedical fields.

Immune responses and neuroinflammation are critically involved in spinal cord injury (SCI). γδ T cells, a small subset of T cells, regulate the inflammation process in many diseases, yet their function in SCI is still poorly understood. In this paper, we demonstrate that mice deficient in γδ T cells (TCRδ−/−) showed improved functional recovery after SCI. γδ T cells are detected at the lesion sites within 24 hours after injury and are predominantly of the Vγ4 subtype and express the inflammatory cytokine IFN-γ. Inactivating IFN-γ signaling in macrophages results in a significantly reduced production of proinflammatory cytokines in the cerebrospinal fluid (CSF) of mice with SCIs and improves functional recovery. Furthermore, treatment of SCI with anti-Vγ4 antibodies has a beneficial effect, similar to that obtained with anti–TNF-α. In SCI patients, γδ T cells are detected in the CSF, and most of them are IFN-γ positive. In conclusion, manipulation of γδ T cell functions may be a potential approach for future SCI treatment.

Limited cellular uptake and inefficient intracellular drug release severely hamper the landscape of polymer drug nanocarriers in cancer chemotherapy. Herein, to address these urgent challenges in tumor treatment simultaneously, we integrated the multivalent choline phosphate (CP) and bioreducible linker into a single polymer chain, designed and synthesized a neoteric bioreducible polymer nanocarrier. The excellent hydrophility of these zwitterionic CP groups endowed high drug loading content and drug loading efficiency of doxorubicin to this drug delivery system (∼22.1 wt %, ∼95.9%). Meanwhile, we found that the multivalent choline phosphate can effectively enhance the internalization efficiency of this drug-loaded nanocarrier over few seconds, and the degree of improvement depended on the CP density in a single polymer chain. In addition, after these nanocarriers entered into the tumor cells, the accelerated cleavage of bioreducible linker made it possible for more cargo escape from the delivery system to cytoplasm to exert their cytostatic effects more efficiently. The enhanced therapeutic efficacy in various cell lines indicated the great potential of this system in anticancer drug delivery applications.

Understanding the mechanisms of brain functions is currently a hot topic but most studies have been focused on the aspects of synchronization and various partial synchronization. We here study this problem from a new angle of signal propagation, where the local (global) propagation may be related to the status of health (mental disorder). We make a case study on the neural network of C. elegans by presenting a framework where one node is chosen as the source node to generate signals and all the other nodes are chosen as the target nodes. We interestingly find that the existence of the unidirectional links is the key element to generate the local firing propagation and the configuration of the unidirectional links will seriously influence the range of firing propagation. In details, our findings include: (i) The unidirectional links prefer the local firing propagation, while the bidirectional links prefer the global firing propagation. (ii) Multiple source nodes will enhance the firing propagation, where the range of firing propagation for choosing the multiple source nodes from different communities is slightly larger than that from the same community. And (iii) a resonance effect of the range of firing propagation on coupling strength is observed, i.e. there is an optimal coupling strength. Moreover, a brief theoretical analysis is provided to explain these results. • A framework is presented to study the firing propagation in real brain networks. • We find that the unidirectional links take the key role in firing propagation. • A resonance effect of the range of firing propagation on coupling strength is discovered. • A theoretical analysis is provided to explain the numerical results. [ABSTRACT FROM AUTHOR]

Post‐injury infection and wound healing are recurrent daily life problems. Therefore, the necessity of developing a biomaterial with antibacterial and wound‐healing properties is paramount. Based on the special porous structure of hydrogel, this work modifies recombinant collagen and quaternary ammonium chitosan and fused them with silver nanoparticles (Ag@mental‐organic framework (Ag@MOF)) with antibacterial properties, and asiaticoside‐loaded liposomes (Lip@AS) with anti‐inflammatory/vascularization effects to form the rColMA/QCSG/LIP@AS/Ag@MOF (RQLAg) hydrogel. The prepared hydrogel possesses good sustainable release capabilities of Ag+and AS and exhibits concentration‐dependent swelling properties, pore size, and compressive strength. Cellular experiments show that the hydrogel exhibits good cell compatibility and promote cell migration, angiogenesis, and M1 macrophage polarization. Additionally, the hydrogels exhibit excellent antibacterial activity against Escherichia coliand Staphylococcus aureusin vitro. In vivo, Sprague Dawley rats burn‐wound infection model showed that the RQLAg hydrogel could efficiently promote wound healing and has stronger healing promoting abilities than those of Aquacel Ag. In summary, the RQLAg hydrogel is expected to be an excellent material for accelerating open wound healing and preventing bacterial infections. The hydrogel composed of recombinant collagen and quaternary ammonium chitosan provides a good platform for biocompatibility. Ag@MOF significantly improves the antibacterial properties of hydrogels. Hydrogels containing asiaticoside‐loaded liposomes (Lip@AS) can effectively promote angiogenesis and macrophage polarization.

Amino acid (aa) metabolism is closely correlated with the pathogenesis of psoriasis; however, details on aa transportation during this process are barely known. Here, we find that SLC38A5, a sodium-dependent neutral aa transporter that counter-transports protons, is markedly upregulated in the psoriatic skin of both human patients and mouse models. SLC38A5 deficiency significantly ameliorates the pathogenesis of psoriasis, indicating a pathogenic role of SLC38A5. Surprisingly, SLC38A5 is almost exclusively expressed in dendritic cells (DCs) when analyzing the psoriatic lesion and mainly locates on the lysosome. Mechanistically, SLC38A5 potentiates lysosomal acidification, which dictates the cleavage and activation of TLR7 with ensuing production of pro-inflammatory cytokines such as interleukin-23 (IL-23) and IL-1β from DCs and eventually aggravates psoriatic inflammation. In summary, this work uncovers an auxiliary mechanism in driving lysosomal acidification, provides inspiring insights for DC biology and psoriasis etiology, and reveals SLC38A5 as a promising therapeutic target for treating psoriasis.

Strategy to improve γδ T cells based cancer immunotherapy by suppressing mTOR signaling. γδ T cells play a critical role in early anti‐tumor immunity and perform cytotoxicity via NKG2D for recognition and multiple cytotoxic factors for tumor killing. Recent studies have demonstrated pivotal roles of mTOR‐mediated metabolism in the maturation, differentiation, and effector function of diverse immune cells, including DCs, NK cells, CD4+T cell subsets, and CD8+T cells, but the role of mTOR signaling in γδ T cells is barely known. Here, we showed that suppressing mTOR signaling in in vitro‐expanded Vγ4 γδ T cells via the mechanistic inhibitor rapamycin enhanced their cytotoxicity against multiple tumor cell lines, and these cells performed better tumor‐suppressing effects upon adoptive therapy. Further investigation revealed that elevated cytotoxicity was a result of up‐regulation of NKG2D and TNF‐α. Moreover, rapamycin treatment significantly decreased the expression of CISH and increased pSTAT5. The inhibition of STAT5 pathways via siRNA interference or a specific inhibitor eliminated the up‐regulation of NKG2D and TNF‐α in rapamycin‐treated Vγ4 γδ T cells. These results uncovered an important role of mTOR signaling in the cytotoxic effector function of γδ T cells and provided a potential strategy to improve γδ T cell‐based cancer immunotherapy.

Mitochondrial protein translation that is essential for aerobic energy production includes four essential steps of the mitochondrial ribosome cycle, namely, initiation, elongation, termination of the polypeptide, and ribosome recycling. Translation termination initiates when a stop codon enters the A site of the mitochondrial ribosome where it is recognized by a dedicated peptide release factor (RF). However, RFs and mechanisms involved in translation in plant mitochondria, especially in monocotyledons, remain largely unknown. Here, we identified a crumpled kernel(crk5allele) mutant, with significantly decreased kernel size, 100-kernel weight, and an embryo-lethal phenotype. The Crk5allele was isolated using map-based cloning and found to encode a mitochondrial localization RF2a. As it is an ortholog of Arabidopsis mitochondrial RF2a, we named the gene ZmmtRF2a. ZmmtRF2ais missing the 5th–7th exons in the crk5resulting in deletion of domains containing motifs GGQ and SPF that are essential for release activity of RF, mitochondrial ribosome binding, and stop codon recognition. Western blot and qRT-PCR analyses indicate that the crk5mutation results in abnormal mitochondrion structure and function. Intriguingly, we observed a feedback loop in the crk5with up-regulated transcript levels detected for several mitochondrial ribosome and mitochondrial-related components, in particular mitochondrial complexes CI, CIV, and a ribosome assembly related PPR. Together, our data support a crucial role for ZmmtRF2ain regulation of mitochondrial structure and function in maize.

γδ T cells make key contributions to tissue physiology and immunosurveillance through two main functional distinct subsets, γδ T1 and γδ T17. m6A methylation plays critical roles in controlling numerous aspects of mRNA metabolism that governs mRNA turnover, gene expression and cellular functional specialization, however, its role in γδ T cells remains less well understood. Here we find that m6A methylation controls the functional specification of γδ T17 vs γδ T1 cells. Mechanistically, m6A methylation prevents the formation of endogenous double-strand RNAs and promotes the degradation of Stat1transcripts, which converge to prevent over-activation of STAT1 signaling and ensuing inhibition of γδ T17. Deleting Mettl3, the key enzyme in m6A methyltransferases complex, in γδ T cells reduces IL-17 production and ameliorates γδ T17-mediated psoriasis. In summary, our work shows that METTL3 mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells.

Seed aging decreases the quality and vigor of crop seeds, thereby causing substantial agricultural and economic losses in crops. To identify genetic differences in seed aging between homozygotes and heterozygotes in maize, the seeds of a set of recombinant inbred lines (RILs) and an immortalized F2(IF2) population were subjected to artificial aging treatments for 0, 2, 3, and 4days under 45ºC and 85% relative humidity and seed vigor was then evaluated in a field experiment. Seed vigor of all entries tested decreased sharply with longer aging treatment and seed vigor decreased more slowly in heterozygotes than in homozygotes. Forty-nine QTL were detected for four measured seed vigor traits in the RIL (28 QTL) and IF2(21 QTL) populations. Only one QTL, qGP5, was detected in both populations, indicating that the genes involved in anti-aging mechanisms differed between inbred lines and hybrids. Several QTL were identified to be responsible for multiple seed vigor traits simultaneously in the RIL and IF2populations under artificial aging conditions. These QTL may include major genes for seed vigor or seed aging. QTL qVI4band qGE3adetected in the RIL population coincided with genes ZmLOX1and ZmPLD1in the same respective chromosomal regions. These QTL would be useful for screening for anti-aging genes in maize breeding.

Because of their unique advantages, fluorescent carbon dots are gaining popularity in various biomedical applications. For these applications, good biosafety is a prerequisite for their use in vivo. Studies have reported the preliminary biocompatibility evaluations of fluorescent carbon dots (mainly cytotoxicity); however, to date, little information is available about their hemocompatibility, which could impede their development from laboratory to bedside. In this work, we evaluated the hemocompatibility of fluorescent carbon dots, which we prepared by hydrothermal carbonization of α-cyclodextrin. The effects of the carbon dots on the structure and function of key blood components were investigated at cellular and molecular levels. In particular, we considered the morphology and lysis of human red blood cells, the structure and conformation of the plasma protein fibrinogen, the complement activation, platelet activation, and in vitro and in vivo blood coagulation. We found that the carbon dots have obvious concentration-dependent effects on the blood components. Overall, concentrations of the fluorescent carbon dots at ≤0.1 mg/mL had few adverse effects on the blood components, but at higher doses, the carbon dots impair the structure and function of the blood components, causing morphological disruptions and lysis of red blood cells, interference in the local microenvironments of fibrinogen, activation of the complement system, and disturbances in the plasma and whole blood coagulation function in vitro. However, the carbon dots tend to activate platelets only at low concentrations. Intravenous administration of the carbon dots at doses up to 50 mg/kg did not impair the blood coagulation function. These results provide valuable information for the clinical application of fluorescent carbon dots.

In practical applications, biomedical materials introduced in vivo may interact with various host cells and/or biomacromolecules and alter their physiological characteristics. Biomaterial-altered cells and/or biomacromolecules may be recognized as “non-self” by the host immune system and may consequently cause further immune responses. In the present work, the gene carrier material branched polyethylenimine (1.8 kDa) (BPEI-1.8k) induced a series of alterations of human red blood cells (RBCs), such as a morphological transition from biconcave disks to spheroechinocytes, vesiculation, a size decrease, a change in surface charge from negative to positive, a cell density reduction, membrane oxidation, and PS externalization. Furthermore, BPEI-1.8k-treated RBCs caused autologous complement activation and were recognized by autologous macrophages. This implies that the biomedical material BPEI-1.8k changed the identity of the RBCs, leading to their recognition by the autologous immune system. This study provides novel insights for the biocompatibility evaluation and clinical application of biomedical materials.

Echo behavior has been found in many systems and takes roles in different aspects. By checking the time series of terminating processes of dynamics events, we find that echo behavior may also exist in brain networks but its mechanism remains unclear. We here study the echo effect on real brain networks by presenting a new framework, which replaces the two perturbations in previous studies by only one perturbation and is thus convenient for theoretical analysis. We interestingly find that echo effect depends on both the phase-resetting parameter and coupling strength, and there is an optimal area of echo effect in phase diagram where the optimal phase-resetting parameter and weak coupling strength are the two necessary conditions. We further reveal that echo comes from a new mechanism of perturbation selected correlation , i.e. a reverse deduced correlation, which explains a more fundamental aspect of echo. Moreover, a theoretical analysis is provided to explain the echo effect, based on the uncoupled brain network. These findings uncover the underlying mechanism why the echoes in brain networks can only happen during the terminating processes, i.e. the condition of optimal phase-resetting or the needed perturbations is provided right before the terminating process while the condition of weak coupling is provided by the terminating process. • Echo behavior was an important topic in various fields of physics and is currently an important topic in the fields of nonlinear dynamics and complex networks. • While the brain network is a unique but typical complex network, its echo effect is undoubtedly important as it may have applications in clinical diagnosis. • Our work focuses on this problem. • In particular, we find the evidence of echo in EEG data of brain dynamics. • Establishing a novel approach for understanding the echo effect in brain dynamics, this paper (1) pioneers a framework of echo by incorporating the first stimulus into the initial conditions , (2) reproduces echo patterns observed in real brain network and reveal an optimal parameter region of echo effect , and (3) introduces an analytical framework that presents a deeper mechanistic insight into the echo effect. • At the same time, our work figures out the two necessary conditions for the echo-like behaviors in EEG Databases. [ABSTRACT FROM AUTHOR]

The ability to transmit and amplify weak signals is fundamental to signal processing of artificial devices in engineering. Using a multilayer feedforward network of coupled double-well oscillators as well as Fitzhugh-Nagumo oscillators, we here investigate the conditions under which a weak signal received by the first layer can be transmitted through the network with or without amplitude attenuation. We find that the coupling strength and the nodes' states of the first layer act as two-state switches, which determine whether the transmission is significantly enhanced or exponentially decreased. We hope this finding is useful for designing artificial signal amplifiers.

Firstly, biodegradable crosslinking agents (BCA) were synthesized by ring‐opening polymerization reaction of lactide, four kinds of which with different molecular weights were got by means of changing the ratio of DL‐lactide(LA) and glycerol(GL). Then a series of poly(N‐vinyl pyrrolidone) (PVP) hydrogels were prepared successfully by radical polymerization of BCA and N‐vinyl pyrrolidone(NVP). Both the ratio of NVP/BCA and the molecular weight of BCA were used to control the performance of PVP hydrogels, which were measured in terms of the ratio of swelling, contact angle, mechanical properties, and biodegradability in vitro. This study showed that increasing both the ratio of NVP/BCA and the molecular weight of BCA resulted in a low crosslinking density of the hydrogels. The crosslinking density played an important role in determining the properties of biodegradable PVP hydrogels. Both the ratio of NVP/BCA and the molecular weight of BCA contributed to high ratio of swelling. A smaller amount of crosslinking agent caused a lower contact angle, while the molecular weight of BCA had little effect on it. In terms of mechanics of hydrogels on both dry and wet conditions, tensile modulus decreased along with decreasing BCA, while the extension at break increased at the beginning and decreased at the end. In the end, measured by mass loss, biodegradability in vitro of hydrogels had two stages: an initial stage with approximately constant loss of mass (stage 1) followed by a stage with rapid mass loss (stage 2). Both increased content and molecular weight of BCA improved the degradation rate of the hydrogels. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1515–1521, 2006

The ideal vaccine delivery systems can not only deliver antigens in intelligent manners but also act as adjuvants. Recently found that Mn2+can effectively stimulate anti-tumor immune responses, and Ca2+can regulate autophagy to promote the cross-presentation of antigens. Thus, we constructed such a manganese-containing multimode vaccine delivery system by using calcium-doped manganese carbonate microspheres (Ca@MnCO3) and perforin-listeria hemolysin (LLO), as termed as Ca@MnCO3/LLO. The two components Ca@MnCO3and LLO, not only act as vaccine adjuvants by themselves, but also contribute to achieve cellular immunity. Among them, Ca@MnCO3microspheres as an excellent Mn2+and Ca2+reservoir, can continuously release adjuvants Mn2+and Ca2+to enhance immune response in dendritic cells, while LLO can contribute to induce lysosomal escape. Particularly, Ca2+was added firstly to MnCO3microspheres to improve the stability and load capacity of the microspheres. Along with the degradation of intracellular Ca@MnCO3microspheres, and the lysosomal membrane-lytic effects of perforin LLO, the Mn2+, Ca2+and OVA were released to the cytoplasm. These outcomes cooperatively promote antigen cross-presentation, elicit CD8+T cell proliferation, and finally achieve prominent anti-tumor effects. The results indicate that the manganese-containing vaccine delivery system Ca@MnCO3/LLO provides a promising platform for the construction of tumor vaccines.

Human cerebral cortex displays various dynamics patterns under different states, however the mechanism how such diverse patterns can be supported by the underlying brain network is still not well understood. Human brain has a unique network structure with different regions of interesting to perform cognitive tasks. Using coupled neural mass oscillators on human cortical network and paying attention to both global and local regions, we observe a new feature of chimera states with multiple spatial scales and a positive correlation between the synchronization preference of local region and the degree of symmetry of the connectivity of the region in the network. Further, we use the concept of effective symmetry in the network to build structural and dynamical hierarchical trees and find close matching between them. These results help to explain the multiple brain rhythms observed in experiments and suggest a generic principle for complex brain network as a structure substrate to support diverse functional patterns.Using the neural mass model on human cortical network, we reveal a new chimera state with multiple spatial scales and provide a way to explain the multiple brain rhythms observed in experiments.

Remote synchronization (RS) is currently a hot topic in the fields of nonlinear dynamics and complex networks, aiming to understand how the distant connections of brain functional network come from its brain structural network. So far, most studies of RS assume the same coupling for all nodes. However, a brain network consists of communities and rich-club where their nodes take different roles. To study their influence to RS, herein we present a model of multiple connected star graphs where the bridge nodes are assumed to represent the rich-club and thus their links are assumed to have different couplings from the non-bridge links. We find that this setup of couplings will seriously influence RS and results in two new phases: (i) the leaf nodes are synchronized each other but they do not synchronize with either the bridge or hub nodes; and (ii) both the leaf and hub nodes are synchronized each other but they do not synchronize with the bridge nodes, i.e. the bridge nodes take the role of new hubs while the hubs become part of leaf nodes, thus named as bridge induced RS. This finding clarifies a misunderstanding in previous studies that RS can be only induced by the hub of star graph and makes us realize that RS is in fact induced by the node taking the role of relay node, no matter it is the hub, bridge, or other node. Further, we show that the bridge induced RS exists for both symmetric and asymmetric couplings of bridge links and can be extended to the case of multiple connected star graphs, thus providing new insights to understand the distant connections of brain functional networks. Finally, a brief theoretical analysis is provided to explain these results. • A model of multiple connected star graphs is proposed for remote synchronization. • Two new states are revealed and one of them is named as " bridge induced RS". • This finding clarifies a misunderstanding that RS can be only induced by the hub. • The findings have been extended to the case of asymmetric couplings of bridge links. • A theoretical analysis is provided to explain the numerical results. [ABSTRACT FROM AUTHOR]

The implications of neural synchronization extend beyond brain function, and can impact the development of artificial neural networks. This paper explores the synchronization of multiple fractional-order fuzzy complex-valued spatiotemporal neural networks (MFOFCVSNNs), which is novel and characterized using fuzzy logic and fractional-order partial differential equations, making it more adaptable and versatile. We first establish a new fractional-order complex-valued partial differential inequality, an integer-order complex-valued partial differential inequality, and an equation. Then, by combining the Lyapunov method with fuzzy set theory, employing newly established inequalities and equations, along with a newly designed fuzzy pinning controller, we derive two linear matrix inequality (LMI) formulations of synchronization criteria for MFOFCVSNNs using a direct non-complex decomposition approach. These criteria exhibit different dependencies on the membership function, with one being independent and the other dependent. Importantly, the criterion based on the membership function demonstrates reduced conservatism compared to its independent counterpart. By leveraging M -matrix theory, we present the synchronization criteria in a concise low-dimensional form. Moreover, this paper extends and enhances previous findings, resulting in reduced conservatism. Finally, we validate our theoretical analysis through numerical simulations. • A new model is proposed-multiple fractional-order fuzzy complex-valued spatiotemporal neural networks, which is novel and characterized using fuzzy logic and fractional-order partial differential equations, making it more adaptable and versatile. • Proposing a novel fuzzy pinning controller for large-scale networks, it streamlines implementation complexity and enhances design flexibility by not requiring identical fuzzy parameters as the model. • Exploring synchronization among multiple fractional-order fuzzy complex-valued delayed spatiotemporal neural networks without utilizing the complex-valued decomposition method. • The membership-function-independent synchronization criterion and the membership-function-dependent synchronization criterion are established. [ABSTRACT FROM AUTHOR]

Remote synchronization (RS) is referred to as the weak synchronization between indirectly coupled nodes (among leaf nodes) while asynchronous between the directed coupled nodes (i.e., hub and leaf nodes). The underlying mechanisms are related to (i) coupling terms indirectly connecting two nearly identical oscillators while having a much different mediator in between, (ii) non-isochronicity of the oscillators. Here we show the effects of uncommon non-isochronicity values of oscillators on the occurrence of RS. In addition, we show clear difference of using either the first order phase approximations of the Stuart–Landau oscillators or Kuramoto–Sakaguchi (KS) models to study RS. By both theoretical and numerical analysis, we show that the critical coupling for synchronization between the directly connected nodes is inversely proportional to the difference value of non-isochronicity. On the contrary, the critical coupling for RS between indirectly connected leaf nodes is determined by the sum of non-isochronicity. In addition, RS may experience fading out after the first appearance when the coupling is progressively increased, which is indeed time delayed phase synchronization. • We show the effects of uncommon non-isochronicity values of oscillators on the occurrence of remote synchronization. • The critical coupling for direct synchronization is inversely proportional to the difference of non-isochronicity. • The critical coupling for indirect synchronization is determined by the sum of non-isochronicity. • Remote synchronization may experience fading out after the first appearance when the coupling is progressively increased. [ABSTRACT FROM AUTHOR]

Traditionally, phase oscillators on a frequency-degree correlated star network provides a building motif for understanding explosive transitions to synchronization and the associated hysteresis behavior. Here we show that a transition from explosive to continuous synchronization is resulted from the frustration term when implementing α c = π / 4 in the Kuramoto-Sakaguchi models on a star. Interestingly, the existence condition for phase locking manifold does not coincide with the backward critical threshold for desynchronization. In addition, the nonlinear effects of the phase shifts are derived analytically, showing a maximal hysteresis range when the frequency-degree correlation is strong enough, i.e., β > β c . On the other hand, the hysteresis range decreases monotonically when β < β c . The maximal hysteresis ranges are not found in other models. Furthermore, numerical results precisely confirm the theoretical predictions. Therefore, the phase shift provides a natural way to control explosive synchronization. • The Kuramoto model on a star graph shows a transition from explosive to continuous synchronization. • The existence condition for phase locking manifold does not coincide with the threshold for desynchronization. • The phase shift shows a maximal hysteresis range when the frequency-degree correlation is strong enough. • The hysteresis range decreases monotonically when β < β c , which is not found in other models. [ABSTRACT FROM AUTHOR]

Remote synchronization (RS) is currently a hot topic in the fields of nonlinear science and complex network and has a close relationship with signal propagation in brain networks. So far, most studies of RS are focused on star graphs. However, realistic networks with RS are much more complicated than a purely star graph, such as various cognitive networks in human brain. Thus, we here present a model of multi-layered community network to extend the study of RS from star graphs to star-like community topologies, i.e. each node of star graph becoming a community. We find that RS may appear in this multi-layered network model, provided that the hub community has a stronger coupling while the leaf communities have a weaker coupling. A measure of RS is introduced to investigate the influence of key parameters such as the frequency distributions, network size, and natural frequency difference between the hub and leaf layers. Moreover, these results have been confirmed in the sub-networks from a real brain network. And a brief theoretical analysis is provided to explain the mechanism of RS in multi-layered community networks. • Remote synchronization (RS) is a characteristic feature of functional brain network but its mechanism is still unclear. • Previous studies on RS are only focused on star graphs and are thus a little far away from the real brain networks. • We construct a multi-layered network model of RS and discuss its parameters dependence. • We confirm RS in the sub-networks from a real brain network. • A theoretical analysis is provided to predict RS, which are agreement with the numerical simulations. [ABSTRACT FROM AUTHOR]

A fundamental observation in nonlinear dynamics is that the asymptotic chaotic invariant sets in many high-dimensional systems are low-dimensional. We argue that such a behavior is typically associated with chaos synchronism. Numerical support using coupled chaotic systems including a class derived from a nonlinear partial differential equation is provided. [Copyright &y& Elsevier]

• We develop a theoretical framework to depict our network model with inter-layer travelers and it works well. • Intense hopping can lead to simultaneous epidemic outbreak in both layers. • Inter-layer hopping plays a "double-sword" role in epidemic spreading in that they can either enhance or suppress the process. • Recurrent outbreaks can occur as a result of inter-layer hopping. Hopping of individuals among distinct layers can induce inter-layer coupling and consequently affect the spreading process in each layer of real world multilayer networks. We articulate a two-layer network model where a fraction of nodes are inter-layer travelers that can hop between layers. We develop a theoretical framework based on the quenched mean-field approximation to accurately predict the epidemic thresholds and final states in both layers. Extensive numerical simulations on synthetic and empirical networks demonstrate that, in the general setting where the structures of the two network layers are asymmetric, intense hopping can lead to simultaneous epidemic outbreak in both layers. In general, the impacts of hopping on the spreading dynamics in the two layers can be quite distinct. As the inter-layer coupling strength is increased, the epidemic threshold of the denser layer increases monotonically, while for the sparser layer, a surprising non-monotonic behavior of the threshold with a minimize value arises. Another finding is that, as a result of hopping, recurrent outbreaks can occur in the sparser layer, providing a plausible explanation for the phenomenon of multiple outbreaks observed from real health data. [ABSTRACT FROM AUTHOR]

• Kuramoto model under an asymmetric and bimodal distribution of initial frequencies has been studied. • Both the Ott–Antonsen analysis and direct numerical simulations are presented. • The system exhibits four different transition routes towards synchronization. • Two types of travelling wave states and the Bellerophon state are characterized. We report on the setting of synchronization in ensembles of phase oscillators under an asymmetric and bimodal distribution of initial frequencies. In particular, by both the Ott–Antonsen reduction and direct numerical simulations we give evidence that the system exhibits four different transition routes towards synchronization, including continuous, discontinuous, and hybrid transitions, depending on the choice of the parameters of the frequency distribution. As the coupling strength increases, several coherent states emerge, such as two types of travelling wave states and the Bellerophon state, which are carefully characterized. [ABSTRACT FROM AUTHOR]

How weak external signals are detected in cognitive subnetworks is one of the key problems to understand how brain functions work. So far, most studies on signal responses are focused on artificial complex networks and it is found that a topological resonance can be induced by the feature of scale-free networks, but little attention has been paid to real brain networks, especially the cognitive subnetworks responsible for signal responses. Herein we address this problem in real brain networks but do not find such a topological resonance, indicating that scale-free is not the key feature of brain networks. Surprisingly, we find a novel resonance effect of signal response induced by heterogeneously mixed positive and negative couplings and thus name it as coupling resonance of signal responses , which explains the mechanism of how brain networks, especially the cognitive subnetworks, detects weak signals. We investigate this coupling resonance in the cases of both heterogeneous couplings and heterogeneous oscillators and find that there is an optimal phenomenon on both the average and standard deviation of coupling strengths. Further, we confirm this coupling resonance in real cognitive subnetworks with weighted links. Finally, we provide a theoretical analysis to show that this coupling resonant comes from the coexistence of the two different local states of neighboring nodes. • A novel effect of coupling resonance of signal responses is revealed. • The key point is the coexistence of mixed positive and negative couplings. • This effect of coupling resonance is confirmed in empirical brain networks. • A theoretical analysis is provided to explain the numerical results. [ABSTRACT FROM AUTHOR]

The study of epidemic spreading on populations of networked individuals has seen recently a great deal of significant progresses. A common point in many of past studies is, however, that there is only one peak of infected density in each single epidemic spreading episode. At variance, real data from different cities over the world suggest that, besides a major single peak trait of infected density, a finite probability exists for a pattern made of two (or multiple) peaks. We show that such a latter feature is distinctive of a multilayered network of interactions, and reveal that a two peaks pattern may emerge from different time delays at which the epidemic spreads in between the two layers. Further, we show that the essential ingredient is a weak coupling condition between the layers themselves, while different degree distributions in the two layers are also helpful. Moreover, an edge-based theory is developed which fully explains all numerical results. Our findings may therefore be of significance for protecting secondary disasters of epidemics, which are definitely undesired in real life. [ABSTRACT FROM AUTHOR]