Heat shock cognate protein 70 is required for rice stripe tenuivirus accumulation and transmission in small brown planthopper.

Rice stripe tenuivirus (RSV) is mainly transmitted by the insect vector small brown planthopper (SBPH, Laodelphax striatellus) in a persistent-propagative manner. Virus transmission is dependent on the interplay between viral proteins and vector factors. Pc2, a nonstructural protein of RSV, plays an important role in virus transmission. However, the vector proteins that interact with Pc2 are unknown. In this study, we identified three SBPH proteins that interact with the N-terminal 381 amino acids of Pc2 (Pc2N) by using a yeast two-hybrid system (Y2H). The interaction of Pc2N with heat shock protein cognate 70 (HSC70) was studied further. HSC70 was verified to interact with RSV Pc2N by biomolecular fluorescence complementation and co-immunoprecipitation assays. HSC70 colocalized with RSV Pc2N in both Sf9 cells and the hemocytes of SBPHs. Inhibition of HSC70 expression via RNA interference reduced virus levels in hemolymph and salivary glands of SBPHs and resulted in decreased virus transmission efficiency. These data provide evidence that a vector protein, HSC70, is employed by RSV to facilitate virus accumulation in the hemolymph and thereby promote virus transmission. These findings are important for a better understanding of the interactions between plant viruses and insect vectors.

Occipital Neuralgia.

PURPOSE OF REVIEW: Occipital neuralgia is a painful condition that affects the posterior aspect of the head and can be difficult to distinguish from other common forms of headaches. This article reviews the anatomy, pathophysiology, clinical presentation, differential diagnosis, diagnostic testing, and management approaches for occipital neuralgia. RECENT FINDINGS: Non-pharmacological treatments aim to alleviate muscle tension and improve posture. Acupuncture shows some promise. The occipital nerve block is considered the first line in a minimally invasive intervention, but the duration of relief may be short term. An onabotulinum toxin A injection may improve the sharp but not the dull component of the pain of occipital neuralgia. Radiofrequency ablation and occipital nerve stimulation may provide effective long-term relief in refractory patients. Surgical decompression, neurotomies, and neurolysis are last-resort treatment options. Occipital neuralgia is a debilitating condition that can be difficult to treat. Studies with larger sample sizes and randomized control trials are needed to further determine the effectiveness and safety of different therapies.

Synergistic antibacterial effects of localized heat and oxidative stress caused by hydroxyl radicals mediated by graphene/iron oxide-based nanocomposites.

This work develops a composite system of reduced graphene oxide (rGO)-iron oxide nanoparticles (rGO-IONP) that can synergistically induce physical and chemical damage to methicillin-resistant Staphylococcus aureus (MRSA) that are present in subcutaneous abscesses. rGO-IONP was synthesized by the chemical deposition of Fe(2+)/Fe(3+) ions on nanosheets of rGO in aqueous ammonia. The antibacterial efficacy of the as-prepared rGO-IONP was evaluated in a mouse model with MRSA-infected subcutaneous abscesses. Upon exposure to a near-infrared laser in vitro, rGO-IONP synergistically generated localized heat and large amounts of hydroxyl radicals, which inactivated MRSA. The in vivo results reveal that combined treatment with localized heat and oxidative stress that is caused by hydroxyl radicals accelerated the healing of wounds associated with MRSA-infected abscesses. The above results demonstrate that an rGO-IONP nanocomposite system that can effectively inactivate multiple-drug-resistant bacteria in subcutaneous infections was successfully developed. FROM THE CLINICAL EDITOR: The emergence of methicillin-resistant S. aureus (MRSA) has posed a significant problem in the clinical setting. Thus, it is imperative to develop new treatment strategies against this. In this study, the authors described the use of reduced graphene oxide (rGO)-iron oxide nanoparticles (rGO-IONP) to induce heat and chemical damage to MRSA. This approach may provide a platform the design of other treatment modalities against multiple-drug-resistant bacteria.

Emerging horizons and prospects of polysaccharide-constructed gels in the realm of wound healing.

Polysaccharides, with the abundant availability, biodegradability, and inherent safety, offer a vast array of promising applications. Leveraging the remarkable attributes of polysaccharides, biomimetic and multifunctional hydrogels have emerged as a compelling avenue for efficacious wound dressing. The gels emulate the innate extracellular biomatrix as well as foster cellular proliferation. The distinctive structural compositions and profusion of functional groups within polysaccharides confer excellent physical/chemical traits as well as distinct restorative involvements. Gels crafted from polysaccharide matrixes serve as a robust defense against bacterial threats, effectively shielding wounds from harm. This comprehensive review delves into wound physiology, accentuating the significance of numerous polysaccharide-based gels in the wound healing context. The discourse encompasses an exploration of polysaccharide hydrogels tailored for diverse wound types, along with an examination of various therapeutic agents encapsulated within hydrogels to facilitate wound repair, incorporating recent patent developments. Within the scope of this manuscript, the perspective of these captivating gels for promoting optimal healing of wounds is vividly depicted. Nevertheless, the pursuit of knowledge remains ongoing, as further research is warranted to bioengineer progressive polysaccharide gels imbued with adaptable features. Such endeavors hold the promise of unlocking substantial potential within the realm of wound healing, propelling us toward multifaceted and sophisticated solutions.

Immunomodulatory Prodrug Micelles Imitate Mild Heat Effects to Reshape Tumor Microenvironment for Enhanced Cancer Immunotherapy.

Physical stimulation with mild heat possesses the notable ability to induce immunomodulation within the tumor microenvironment (TME). It transforms the immunosuppressive TME into an immune-active state, making tumors more receptive to immune checkpoint inhibitor (ICI) therapy. Transient receptor potential vanilloid 1 (TRPV1), which can be activated by mild heat, holds the potential to induce these alterations in the TME. However, achieving precise temperature control within tumors while protecting neighboring tissues remains a significant challenge when using external heat sources. Taking inspiration from the heat sensation elicited by capsaicin-containing products activating TRPV1, this study employs capsaicin to chemically stimulate TRPV1, imitating immunomodulatory benefits akin to those induced by mild heat. This involves developing a glutathione (GSH)-responsive immunomodulatory prodrug micelle system to deliver capsaicin and an ICI (BMS202) concurrently. Following intravenous administration, the prodrug micelles accumulate at the tumor site through the enhanced permeability and retention effect. Within the GSH-rich TME, the micelles disintegrate and release capsaicin and BMS202. The released capsaicin activates TRPV1 expressed in the TME, enhancing programmed death ligand 1 expression on tumor cell surfaces and promoting T cell recruitment into the TME, rendering it more immunologically active. Meanwhile, the liberated BMS202 blocks immune checkpoints on tumor cells and T cells, activating the recruited T cells and ultimately eradicating the tumors. This innovative strategy represents a comprehensive approach to fine-tune the TME, significantly amplifying the effectiveness of cancer immunotherapy by exploiting the TRPV1 pathway and enabling in situ control of immunomodulation within the TME.

Dual-network carboxymethyl chitosan conductive hydrogels for multifunctional sensors and high-performance triboelectric nanogenerators.

With the development of technology, there is a growing demand for wearable electronics that can fulfill different application scenarios. Hydrogel-based sensors are considered ideal candidates for realizing multifunctional wearable flexible devices. However, there are great challenges in preparing hydrogel-based sensors with both superior mechanical and electrical properties. Herein, we report a composite conductive hydrogel prepared by using a dynamically crosslinked carboxymethyl chitosan network and a covalently crosslinked polymer network, and carboxylated carbon nanotubes as conductive filler. The carboxymethyl chitosan-based hydrogels had excellent mechanical properties and strength (tensile strength of 475.4 kPa, and compressive strength of 1.9 MPa) and ultra-high conductivity (0.19 S·cm-1). Based on the above characteristics, the hydrogel could accurately identify the movement signals of the human body and different writing signals, and achieve encrypted transmission of signals, broadening the application scenarios. In addition, a triboelectric nanogenerator (TENG) was fabricated based on the hydrogel, which had an outstanding output performance with open-circuit voltage of 336 V, short-circuit current of 18 µA, transferred charge of 52 nC and maximum power density of 340 mW·m-2, and could power small devices. This work is expected to provide new ideas for the development of self-powered, multi-functional wearable, and flexible polysaccharide-based devices.

Liquid-free ionic conductive elastomers with high mechanical properties and ionic conductivity for multifunctional sensors and triboelectric nanogenerators.

Liquid-free ionic conductive elastomers (ICEs) are ideal materials for constructing flexible electronic devices by avoiding the limitations of liquid components. However, developing all-solid-state ionic conductors with high mechanical strength, high ionic conductivity, excellent healing, and recyclability remains a great challenge. Herein, a series of liquid-free polyurethane-based ICEs with a double dynamic crosslinked structure are reported. As a result of interactions between multiple dynamic bonds (multi-level hydrogen bonds, disulfide bonds, and dynamic D-A bonds) and lithium-oxygen bonds, the optimal ICE exhibited a high mechanical strength (1.18 MPa), excellent ionic conductivity (0.14 mS cm-1), desirable healing capacity (healing efficiency >95%), and recyclability. A multi-functional wearable sensor based on the novel ICE enabled real-time and rapid detection of various human activities and enabled recognizing writing signals and encrypted information transmission. A triboelectric nanogenerator based on the novel ICE exhibited an excellent open-circuit voltage of 464 V, a short-circuit current of 16 µA, a transferred charge of 50 nC, and a power density of 720 mW m-2, enabling powering of small-scale electronic products. This study provides a feasible strategy for designing flexible sensor products and healing, self-powered devices, with promising prospects for application in soft ionic electronics.

Cancer immunotherapy using a membrane-bound interleukin-12 with B7-1 transmembrane and cytoplasmic domains.

Interleukin-12 (IL-12) has potent antitumor activity, but its clinical application is limited by severe systemic toxicity, which might be alleviated by the use of membrane-anchored IL-12. In the present study, a new membrane-bound IL-12 containing murine single-chain IL-12 and B7-1 transmembrane and cytoplasmic domains (scIL-12-B7TM) was constructed and its efficacy in cancer treatment examined and its protective antitumor mechanism investigated. Surface expression of scIL-12-B7TM on colon adenocarcinoma cells significantly inhibited the growth of subcutaneous tumors, suppressed lung metastasis, and resulted in local and systemic suppression of unmodified tumors. Intratumoral injection of an adenoviral vector encoding scIL-12-B7TM not only resulted in complete regression of a majority of local tumors, but also significantly suppressed the growth of distant, untreated tumors. Moreover, mice that had been treated with scIL-12-B7TM developed memory responses against subsequent tumor challenge. Immunohistochemical staining and in vivo depletion of lymphocyte subpopulations demonstrated that both CD8(+) T cells and CD4(+) T cells contributed to the antitumor activity of scIL-12-B7TM. Importantly, the potent antitumor activities of scIL-12-B7TM were achieved with only negligible amounts of IL-12 in the circulation. Our data demonstrate that cancer immunotherapy using membrane-bound IL-12 has the advantage of minimizing systemic IL-12 levels without compromising its antitumor efficacy.

Twinning Behavior, Microstructure Evolution and Mechanical Property of Random-Orientated ZK60 Mg Alloy Compressed at Room Temperature.

In this study, the uniaxial compression of random orientation ZK60 Mg alloy to different strains was performed at room temperature. The microstructure evolution was characterized mainly using electron backscattered diffraction (EBSD), and the mechanical property was evaluated by the Vickers hardness test. During compression, extension twins nucleated, grew, and engulfed the grain. Twins form a texture with the c-axis parallel to the compression direction. With the massive nucleation and expansion of extension twins during compression, the twin boundary (TB) brought the grain refinement, and the twin boundary-dislocation interaction significantly increased the strain hardening rate of ZK60 Mg alloy, both leading to its significantly increasement of the hardness.

Biomimetic Platelet Nanomotors for Site-Specific Thrombolysis and Ischemic Injury Alleviation.

Due to the mortality associated with thrombosis and its high recurrence rate, there is a need to investigate antithrombotic approaches. Noninvasive site-specific thrombolysis is a current approach being used; however, its usage is characterized by the following limitations: low targeting efficiency, poor ability to penetrate clots, rapid half-life, lack of vascular restoration mechanisms, and risk of thrombus recurrence that is comparable to that of traditional pharmacological thrombolysis agents. Therefore, it is vital to develop an alternative technique that can overcome the aforementioned limitations. To this end, a cotton-ball-shaped platelet (PLT)-mimetic self-assembly framework engineered with a phototherapeutic poly(3,4-ethylenedioxythiophene) (PEDOT) platform has been developed. This platform is capable of delivering a synthetic peptide derived from hirudin P6 (P6) to thrombus lesions, forming P6@PEDOT@PLT nanomotors for noninvasive site-specific thrombolysis, effective anticoagulation, and vascular restoration. Regulated by P-selectin mediation, the P6@PEDOT@PLT nanomotors target the thrombus site and subsequently rupture under near-infrared (NIR) irradiation, achieving desirable sequential drug delivery. Furthermore, the movement ability of the P6@PEDOT@PLT nanomotors under NIR irradiation enables effective penetration deep into thrombus lesions, enhancing bioavailability. Biodistribution analyses have shown that the administered P6@PEDOT@PLT nanomotors exhibit extended circulation time and metabolic capabilities. In addition, the photothermal therapy/photoelectric therapy combination can significantly augment the effectiveness (ca. 72%) of thrombolysis. Consequently, the precisely delivered drug and the resultant phototherapeutic-driven heat-shock protein, immunomodulatory, anti-inflammatory, and inhibitory plasminogen activator inhibitor-1 (PAI-1) activities can restore vessels and effectively prevent rethrombosis. The described biomimetic P6@PEDOT@PLT nanomotors represent a promising option for improving the efficacy of antithrombotic therapy in thrombus-related illnesses.

Hydrogel-delivered GM-CSF overcomes nonresponsiveness to hepatitis B vaccine through the recruitment and activation of dendritic cells.

The standard hepatitis B surface Ag (HBsAg) vaccine fails to induce anti-hepatitis B surface Abs in 5-10% of healthy subjects, a phenomenon known as HBsAg nonresponsiveness, which is closely related to HLA class II alleles and impaired Th cell responses to HBsAg in these subjects. We hypothesized that GM-CSF, a potent adjuvant in enhancing the Ag-presentation activity of APCs, might help to generate Th cell responses in nonresponders, subsequently providing help for B cells to produce anti-hepatitis B surface Abs. We used a thermosensitive biodegradable copolymer (hydrogel) system to codeliver HBsAg and GM-CSF to achieve maximal local cytokine activity at the injection site. In responder mouse strains, hydrogel-formulated HBsAg plus GM-CSF (Gel/HBs+GM) vaccine elicited much greater anti-hepatitis B surface Ab titers and Th cell proliferative responses than a commercial aluminum-formulated HBsAg vaccine or free HBsAg. The adjuvant effect of the Gel/HBs+GM vaccine was dependent upon the local release of GM-CSF. More importantly, the Gel/HBs+GM vaccine elicited high HBsAg-specific Ab titers and Th cell responses in B10.M mice, a mouse strain that does not respond to the current HBsAg vaccine because of its H-2 haplotype. Analysis of the draining lymph nodes of Gel/HBs+GM vaccine-treated mice revealed an elevated number of CD11c(+) dendritic cells showing enhanced expression of MHC class II and a variety of costimulatory molecules. These results demonstrate that hydrogel-formulated GM-CSF might represent a simple and effective method to generate next-generation hepatitis B virus vaccines for inducing anti-hepatitis B surface Abs in nonresponders.

Molecularly Targeted Photothermal Ablation of Epidermal Growth Factor Receptor-Expressing Cancer Cells with a Polypyrrole-Iron Oxide-Afatinib Nanocomposite.

Near-infrared-photothermal therapy (NIR-PTT) is a potential modality for cancer treatment. Directing photothermal effects specifically to cancer cells may enhance the therapeutic index for the best treatment outcome. While epithelial growth factor receptor (EGFR) is commonly overexpressed/genetically altered in human malignancy, it remains unknown whether targeting EGFR with tyrosine kinase inhibitor (TKI)-conjugated nanoparticles may direct NIR-PTT to cancers with cellular precision. In the present study, we tested this possibility through the fabrication of a polypyrrole-iron oxide-afatinib nanocomposite (PIA-NC). In the PIA-NC, a biocompatible and photothermally conductive polymer (polypyrrole) was conjugated to a TKI (afatinib) that binds to overexpressed wild-type EGFR without overt cytotoxicity. A Fenton catalyst (iron oxide) was further encapsulated in the NC to drive the intracellular ROS surge upon heat activation. Diverse physical and chemical characterization experiments were conducted. Particle internalization, cytotoxicity, ROS production, and apoptosis in EGFR-positive and -negative cell lines were investigated in the presence and absence of NIR. We found that the PIA-NCs were stable with a size of 243 nm and a zeta potential of +35 mV. These PIA-NCs were readily internalized close to the cell membrane by all types of cells used in the study. The Fourier transform infrared spectra showed 3295 cm-1 peaks; substantial O-H stretching was seen, with significant C=C stretching at 1637 cm-1; and a modest appearance of C-O-H bending at 1444 cm-1 confirmed the chemical conjugation of afatinib but not iron oxide to the NC. At a NIR-PTT energy level that has a minimal cytotoxic effect, PIA-NC significantly sensitizes EGFR-overexpressing A549 lung cancer cells to NIR-PTT-induced cytotoxicity at a rate of 70%, but in EGFR-negative 3T3 fibroblasts the rate was 30%. Within 1 min of NIR-PTT, a surge of intracellular ROS was found in PIA-NC-treated A549 cells. This was followed by early induction of cellular apoptosis for 54 ± 0.081% of A549 cells. The number of viable cells was less than a quarter of a percent. Viability levels of A549 cells that had been treated with NIR or PIA were only 50 ± 0.216% and 80 ± 0.216%, respectively. Only 10 ± 0.816% of NIH3T3 cells had undergone necrosis, meaning that 90 ± 0.124% were alive. Viability levels were 65 ± 0.081% and 81 ± 0.2%, respectively, when only NIR and PIA were used. PIA binding was effective against A549 cells but not against NIH3T3 cells. The outcome revealed that higher levels of NC + NIR exposure caused cancer cells to produce more ROS. In summary, our findings proved that a molecularly targeted NC provides an orchestrated platform for cancer cell-specific delivery of NIR-PTT. The geometric proximity design indicates a novel approach to minimizing the off-target biological effects of NIR-PTT. The potential of PIA-NC to be further developed into real-world application warrants further investigation.

[Design of high performance DSP-based gradient calculation module for MRI].

A gradient calculation module based on high performance DSP was designed to meet the needs of digital MRI spectrometer. According to the requirements of users, this apparatus can achieve rotation transformation, pre-emphasis, shimming and other gradient calculation functions in a single chip of DSP. It then outputs gradient waveform data of channel X, Y, Z and shimming data of channel B0. Experiments show that the design has good versatility and can satisfy the functional, speed and accuracy requirements of MRI gradient calculation. It provides a practical gradient calculation solution for the development of digital spectrometer.

Pollen-Mimetic Metal-Organic Frameworks with Tunable Spike-Like Nanostructures That Promote Cell Interactions to Improve Antigen-Specific Humoral Immunity.

The exine capsules of pollen particles exhibit a variety of characteristic surface morphologies that promote their cell interactions; their use as antigen carriers for vaccination has been proposed. However, the allergy-causing substances in pollen particles may not all be removed, even by vigorous chemical treatments. To resolve this issue, this work develops systemic approaches for synthesizing pollen-mimetic metal-organic frameworks (MOFs), which comprise aluminum (Al) ions and an organic linker (2-aminoterephthalic acid), with tunable spike-like nanostructures on their surfaces. The as-synthesized MOFs act not only as a delivery vehicle that carries a model antigen (ovalbumin, OVA) but also as an adjuvant (Al). Scanning and transmission electron microscopies images reveal that the aspect ratio of the nanospikes that are grown on the MOFs can be controlled. A higher aspect ratio of the nanospikes on the MOFs is associated with greater cell attachment and faster and more efficient phagocytosis in cells, which results in greater expressions of pro-inflammatory cytokines. Consequently, a more robust immune response against the antigen of interest is elicited. These findings have broad implications for the rational design of the future antigen/adjuvant-presenting particles for vaccination.

Genomic Context Differs Between Human Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy.

Background Inherited cardiomyopathies display variable penetrance and expression, and a component of phenotypic variation is genetically determined. To evaluate the genetic contribution to this variable expression, we compared protein coding variation in the genomes of those with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Methods and Results Nonsynonymous single-nucleotide variants (nsSNVs) were ascertained using whole genome sequencing from familial cases of HCM (n=56) or DCM (n=70) and correlated with echocardiographic information. Focusing on nsSNVs in 102 genes linked to inherited cardiomyopathies, we correlated the number of nsSNVs per person with left ventricular measurements. Principal component analysis and generalized linear models were applied to identify the probability of cardiomyopathy type as it related to the number of nsSNVs in cardiomyopathy genes. The probability of having DCM significantly increased as the number of cardiomyopathy gene nsSNVs per person increased. The increase in nsSNVs in cardiomyopathy genes significantly associated with reduced left ventricular ejection fraction and increased left ventricular diameter for individuals carrying a DCM diagnosis, but not for those with HCM. Resampling was used to identify genes with aberrant cumulative allele frequencies, identifying potential modifier genes for cardiomyopathy. Conclusions Participants with DCM had more nsSNVs per person in cardiomyopathy genes than participants with HCM. The nsSNV burden in cardiomyopathy genes did not correlate with the probability or manifestation of left ventricular measures in HCM. These findings support the concept that increased variation in cardiomyopathy genes creates a genetic background that predisposes to DCM and increased disease severity.

Differential antitumor effect of interleukin-12 family cytokines on orthotopic hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most difficult cancers to treat. The interleukin (IL)-12 family cytokines, including IL-12, IL-23 and IL-27, display overlapping, but not redundant, roles in regulating lymphocyte subpopulations. IL-12 is known as a potent antitumor cytokine, whereas the results of the antitumor effect of IL-23 and IL-27 are inconsistent. The present study aimed to directly compare the relative antitumor efficacy of these three IL-12 family cytokines on HCC. METHODS: A murine orthotopic BNL HCC model, in which the tumor is located in an environment heavily populated with different lymphocyte subsets, was established. The hepatotropic adeno-associated virus serotype 8 (AAV8) vector was used to deliver the cytokine genes aiming to achieve sustained cytokine expression in the liver. RESULTS: AAV8/IL-12 treatment significantly reduced hepatic metastases and prolonged survival time, whereas treatment with AAV8/IL-23 or AAV8/IL-27 had only moderate antitumor effects at a high dose. The antitumor efficacy of these cytokines was positively correlated with their ability to regulate hepatic T cells, natural killer cells and natural killer T cells, with IL-12 greatly increasing the number and activation status of these cells, whereas IL-27 had no effect and IL-23 had a negative effect. AAV8/IL-12 treatment also resulted in a marked decrease in tumor vessel density, which was not observed with AAV8/IL-23 and AAV8/IL-27 treatment. CONCLUSIONS: The data obtained in the present study highlight the importance of local lymphocytes and anti-angiogenesis for influencing the antitumor activity of these three IL-12 family cytokines and suggest that IL-12 is the best candidate for treating HCC.

Modulation of tumor microenvironment using a TLR-7/8 agonist-loaded nanoparticle system that exerts low-temperature hyperthermia and immunotherapy for in situ cancer vaccination.

Most cancer vaccines under development are associated with defined tumor antigens rather than with all antigens of whole tumor cells, limiting the anti-tumor immune responses that they elicit. This work proposes an immunomodulator (R848)-loaded nanoparticle system (R848@NPs) that can absorb near-infrared light (+NIR) to cause low-temperature hyperthermia that interacts synergistically with its loaded R848 to relieve the tumor-mediated immunosuppressive microenvironment, generating robust anti-tumor memory immunity. In vitro results reveal that the R848@NPs could be effectively internalized by dendritic cells, causing their maturation and the subsequent regulation of their anti-tumor immune responses. Post-treatment observations in mice in which tumors were heat-treated at high temperatures reveal that tumor growth was significantly inhibited initially but not in the longer term, while low-temperature hyperthermia or immunotherapy alone simply delayed tumor growth. In contrast, a combined therapy that involved low-temperature hyperthermia and immunotherapy using R848@NPs/+NIR induced a long-lasting immunologic memory and consequently inhibited tumor growth and prevented cancer recurrence and metastasis. These results suggest that the method that is proposed herein is promising for generating cancer vaccines in situ, by using the tumor itself as the antigen source and the introduced R848@NPs/+NIR to generate a long-term anti-tumor immunity, for personalized immunotherapy.

Single-injecting, bioinspired nanocomposite hydrogel that can recruit host immune cells in situ to elicit potent and long-lasting humoral immune responses.

Vaccination is an effective medical intervention for preventing disease. However, without an adjuvant, most subunit vaccines are poorly immunogenic. This work develops a bioinspired nanocomposite hyaluronic acid hydrogel system that incorporates N-trimethyl chitosan nanoparticles (TMC/NPs) that carry a model subunit vaccine ovalbumin (OVA) that can elicit a potent and prolonged antigen-specific humoral response. Experimental results indicate that the nanocomposite hydrogel system (NPs-Gel) can retain a large proportion of its TMC/NPs that are bonded by covalent/electrostatic interactions and extend the release of the encapsulated OVA, enabling their localization at the site of hydrogel injection. The positively charged TMC/NPs can be effectively internalized by dendritic cells, significantly augmenting their maturation, suggesting that TMC can function as an adjuvant-based OVA delivery system. Upon subcutaneous implantation in mice, the NPs-Gel acts as an in situ depot that recruits and concentrates immune cells. The TMC/NPs that do not have any specific interactions with the hydrogel network are released rapidly and internalized by the neighboring immune cells, providing a priming dose, while those retained inside the NPs-Gel are ingested by the recruited and concentrated immune cells over time, acting as a booster dose, eliciting high titers of OVA-specific antibody responses. These experimental results suggest particulate vaccines that are integrated in such a bioinspired hydrogel system may be used as single-injection prime-boost vaccines, enabling effective and persistent humoral immune responses.

[Algorithm of digital demodulation and filtering in MRI spectrometers].

In the design of RF receiver of the digital MRI spectrometer console, a digital demodulation and filtering algorithm is presented in this thesis. The MR signals are firstly converted to digital signals by the A/D converter, and then quadrature-demodulated from high frequency carrier wave. The CIC filter, half-band filter and linear phase FIR filter are designed to process the cascaded filtering and decimation of the demodulated signals. This method achieves a satisfying processing speed and filtering effect, and also reduces the data size obviously. The experiment based on the permanent magnetism resonance imaging system proves its effectiveness and practicability.

In situ self-spray coating system that can uniformly disperse a poorly water-soluble H2S donor on the colorectal surface to treat inflammatory bowel diseases.

Inflammatory bowel disease (IBD) is an intestinal inflammatory disorder. Exogenous hydrogen sulfide (H2S) donors such as diallyl trisulfide (DATS) have been used as anti-inflammatory mediators. However, an ideal method of administering DATS has yet to be established owing to its poor water solubility. Herein, a self-spray coating system that is derived from a DATS-loaded capsule with foaming capability (CAP-w-FC) is proposed for treating colitis. Following the rectal administration of CAP-w-FC into rats bearing colitis and its subsequent dissolution in the intestinal fluid, a spray coating system is self-assembled in situ. This system greatly promotes the dissolution of the poorly water-soluble DATS by producing nano-scaled micellar particles that are sprayed onto the large luminal surface of the colorectal tract. Following the internalization of the micellar particles by colon epithelial cells, their loaded DATS reacts with intracellular glutathione to yield H2S. This exogenous H2S then diffuses through plasma membranes to carry out its biological functions, including suppressing the overproduction of pro-inflammatory cytokines, inhibiting the adhesion of macrophages on the vascular endothelium, and repairing colonic inflamed tissues. Analytical results demonstrate that this self-spray coating system may be used as a unique drug delivery technique for covering the large colorectal surface to treat IBD.