Search

Autologous tumor cell membrane antigen-based vaccines (TMVs) have garnered extensive attention as personalized immunotherapy. However, patients who take TMVs therapy usually undergo various treatments prior to surgery, and these processes modulate the immunogenicity of the tumor membrane and the tumor immune microenvironment. Herein, we investigate the impact of preoperative chemotherapy on the efficacy of TMVs. Liposomal doxorubicin ameliorates the immunosuppressive tumor microenvironment and enhances immunological molecule expression on the tumor membrane. This has driven TMVs to elicit a more robust immune response than doxorubicin, resulting in more effective immune protection. The TMVs formulated from liposomal doxorubicin-treated tumors induce superior dendritic cell maturation and T cell activation compared to doxorubicin, thus demonstrating better efficacy in preventing recurrence and metastasis in the postoperative murine model. Collectively, our study suggests that chemotherapy can induce immunomodulatory changes that augment the therapeutic potential of immunotherapy and provides valuable insights into the clinical utilization of TMVs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the frailty status of inpatients with chronic heart failure (CHF) and analyse its influencing factors, so as to provide evidence for the early identification of high-risk groups and frailty management., Background: Early identification of frailty can guide the development and implementation of holistic and individualized treatment plans. However, at present, the frailty of patients with CHF has not attracted enough attention., Design: A cross-sectional study., Methods: From June 2022 to June 2023, a convenience sample of 256 participants were recruited at a hospital in China. Multivariate logistic regression analysis was used to explore the influencing factors of frailty in patients with CHF, and an ROC curve was drawn to determine the cut-off values for each influencing factor. STROBE checklist guides the reporting of the manuscript., Results: A total of 270 questionnaires were sent out during the survey, and 256 valid questionnaires were ultimately recovered, resulting in an effective recovery rate of 94.8%. The incidence of frailty in hospitalized patients with CHF was 68.75%. Multivariable logistic regression analysis showed that age, self-care ability, nutritional risk, Kinesiophobia and NT-proBNP were risk factors for frailty, while albumin and LVEF were protective factors., Conclusion: Multidimensional frailty was prevalent in hospitalized patients with CHF. Medical staff should take measures as early as possible from the aspects of exercise, nutrition, psychology and disease to delay the occurrence and development of frailty and reduce the occurrence of clinical adverse events caused by frailty., Relevance to Clinical Practice: This study emphasizes the importance of the early identification of multidimensional frailty and measures can be taken to delay the occurrence and development of frailty through exercise, nutrition, psychology and disease treatment., Patient or Public Contribution: Patients contributed through sharing their information required for the case report form and filling out questionnaires., (© 2024 John Wiley & Sons Ltd.)

The potential for mitigating intestinal inflammation through the gut-bone axis in the treatment of osteoporosis is significant. While various gut-derived postbiotics or bacterial metabolites have been created as dietary supplements to prevent or reverse bone loss, their efficacy and safety still need improvement. Herein, a colon-targeted drug delivery system is developed using surface engineering of polyvinyl butyrate nanoparticles by shellac resin to achieve sustained release of postbiotics butyric acid at the colorectal site. These engineered postbiotics nanoparticles can effectively suppress macrophage inflammatory activation, modulate the redox balance, and regulate the composition of the gut microbiota, thereby restoring epithelial barriers, inhibiting bacterial invasion, and down-regulating pro-inflammatory responses. As a result, the remission of systemic inflammation is accompanied by a rebalancing of osteoblast and osteoclast activity, alleviating inflammatory bowel disease-related and post-menopausal bone loss. Specifically, the treatment of engineered postbiotics nanoparticles can also improve the quality and quantity of bone with restoration of deteriorative mechanical properties, which indicating a therapeutic potential on fracture prevention. This study provides valuable insights into the gut-bone axis and establishes a promising and safe therapeutic strategy for osteoporosis., Competing Interests: Competing interests: T.Y., R.B., Z.W., Y.Q., R.Z., B.H., and G.N. are inventors on a filed provisional application for China patent No. 2024115617826 (“A composite butyrate nanoparticle and its synthesis strategy and application”) submitted by Peking University School of Stomatology and the National Center for Nanoscience and Technology that covers the synthesis strategy and potential therapeutic use of BuNP@Shellac for inflammatory bowel disease and osteoporosis treatment. T.Y., R.B., Z.W., Y.Q., R.Z., B.H., and G.N. declare no other competing interests. J.W. and Y.W. declare no competing interests., (© 2024. The Author(s).)

The development of prophylactic cancer vaccines typically involves the selection of combinations of tumour-associated antigens, tumour-specific antigens and neoantigens. Here we show that membranes from induced pluripotent stem cells can serve as a tumour-antigen pool, and that a nanoparticle vaccine consisting of self-assembled commercial adjuvants wrapped by such membranes robustly stimulated innate immunity, evaded antigen-specific tolerance and activated B-cell and T-cell responses, which were mediated by epitopes from the abundant number of antigens shared between the membranes of tumour cells and pluripotent stem cells. In mice, the vaccine elicited systemic antitumour memory T-cell and B-cell responses as well as tumour-specific immune responses after a tumour challenge, and inhibited the progression of melanoma, colon cancer, breast cancer and post-operative lung metastases. Harnessing antigens shared by pluripotent stem cell membranes and tumour membranes may facilitate the development of universal cancer vaccines., Competing Interests: Competing interests: The authors G.N., R.Z. and N.L. are inventors on a filed provisional application for China patent no. CN2024103159244 (An immune composition and its application) and no. CN2024113741833 (Tumour-shared surface antigen epitope peptide and its screening method), submitted by the National Center for Nanoscience and Technology, covering the potential application of tumour prevention of iPM nanovax. The authors declare no other competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Pyro-phototronic effect (PPE) can significantly boost the performance of hybrid perovskite (HPs) photodetectors due to the effective modulation of photogenerated charge carrier separations, transportation, and extraction. However, there are few reports on the application of PPE in lead-free HPs. Herein, a polar lead-free HP (1,3-BMACH)BiBr 5 [1,3-BMACH = 1,3- bis (aminomethyl)cyclohexane] is synthesized and realized broadband self-powered photoresponse from X-rays to near-infrared (NIR) through the PPE. Particularly, this light-induced PPE in lead-free HPs breaks the limitation of the optical band gap, making them suitable for broadband self-powered photodetection. Under 405 nm illumination, compared with a purely photovoltaic system, I photo+pyro is boosted by 3100%, and R and D * are both enhanced by 260% after coupled PPE. It is particularly interesting that an obvious X-ray-induced PPE phenomenon is also observed, which endows (1,3-BMACH)BiBr 5 with a high sensitivity of 154 μC Gy -1 cm -2 and a low detection limit of 307 nGy s -1 under the self-powered mode. The implementation of light-induced PPE from X-rays to NIR in lead-free HPs provides a new approach for constructing environmentally friendly, broadband, and self-powered optoelectronic devices in the future.

Cultivated peanut (Arachis hypogaea L.) is a widely grown oilseed crop worldwide; however, the events leading to its origin and diversification are not fully understood. Here by combining chloroplast and whole-genome sequence data from a large germplasm collection, we show that the two subspecies of A. hypogaea (hypogaea and fastigiata) likely arose from distinct allopolyploidization and domestication events. Peanut genetic clusters were then differentiated in relation to dissemination routes and breeding efforts. A combination of linkage mapping and genome-wide association studies allowed us to characterize genes and genomic regions related to main peanut morpho-agronomic traits, namely flowering pattern, inner tegument color, growth habit, pod/seed weight and oil content. Together, our findings shed light on the evolutionary history and phenotypic diversification of peanuts and might be of broad interest to plant breeders., (© 2024. The Author(s).)

Ferroelectric materials with Curie temperature ( T c ) below room temperature severely limit their practical applications. Although research on hybrid perovskite photoferroelectrics is ongoing, effective regulation of T c still poses significant challenges. Herein, we utilized the cationic size effect to successfully regulate the T c of hybrid perovskite photoferroelectric semiconductors. As the perovskitizer was replaced by a smaller-sized MA + (methylammonium) with a larger-sized EA + (ethylammonium), not only was the ferroelectricity of the hybrid perovskite well maintained but the T c of (PA) 2 (MA) 2 Pb 3 Br 10 (315 K) to (PA) 2 (EA) 2 Pb 3 Br 10 (385 K) (PA is n -propylaminium) increased by 70 K, which was mainly due to the significant increase in the energy barriers that the system needed to overcome during the phase transition. Subsequently, we achieved efficient self-powered X-ray detection through the ferroelectric-induced bulk photovoltaic effect (BPVE) in (PA) 2 (EA) 2 Pb 3 Br 10 . The devices based on (PA) 2 (EA) 2 Pb 3 Br 10 single crystals exhibit an outstanding sensitivity of 95 μC Gy -1 cm -2 and a low detection limit of 239 nGy s -1 at 0 V bias under X-ray radiation. This study provides an effective approach for designing and constructing high-temperature multilayer photoferroelectric semiconductors in the future.

The objective of this study was to explore changes in miRNA133 levels as a basis for clinical diagnostic markers in patients with acute myocardial infarction (AMI). A total of 100 chest pain patient cases admitted to a hospital from June 2021 to December 2022 were used. The study involved the selection of 50 patients: 25 patients with unstable undetermined heart pain and 25 healthy subjects were included in the control group of 50 patients with non-AMI patients. Meanwhile, 50 patients with AMI were designated as the experimental group. Changes in miRNA133 levels in patients' plasma were analyzed for expression using quantitative fluorescence analysis. When the serum TPI, plasma NT-ProBNP, glycosylated hemoglobin, and plasma D-dimer index values were compared between the control and experimental groups, there was a statistically significant difference (P < .05). mi-RNA-133 had a mean plasma level value of 2.60 ± 1.01, the mean level value of mi-RNA-133 in patients with non-AMI was 1.34 ± 1.18, and the patients in the AMI group showed significantly high values of the mean plasma level of mi-RNA-133. The relative expression level value of cTnl in patients with AMI was 10.84 ± 12.64. Of the specificity and sensitivity diagnostics, mi-RNA-133 had the best diagnostic effect. The area under mi-RNA-133 in the regression curve was 95.4%, the specificity of the whole combination of indicators was 89.4% and the sensitivity was 100%. Finally, the correlation between mi-RNA-133 and white blood cell count (WBC) and TG was statistically significant (P < .05). In conclusion, changes in the level of mi-RNA-133 may be an important marker for diagnosing the status of patients with AMI, while a faster and more accurate method will emerge along with the improvement of the detection technology, and at the same time, due to the variability of the study cases and other limitations, further research will be carried out subsequently., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The gut microbiota is an integral component of the colorectal cancer (CRC) microenvironment and is intimately associated with CRC initiation, progression, and therapeutic outcomes. We reviewed recent advancements in utilizing nanotechnology for modulating gut microbiota, discussing strategies and the mechanisms underlying their design. For future nanomedicine design, we propose a 5I principle for individualized nanomedicine in CRC management., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

Osteoarthritis (OA) is a chronic joint disease characterized by progressive degeneration of articular cartilage. A challenge in the development of disease-modifying drugs is effective delivery to chondrocytes. The unique structure of the joint promotes rapid clearance of drugs through synovial fluid, and the dense and avascular cartilage extracellular matrix (ECM) limits drug penetration. Here, we show that poly(lactide- co -glycolic acid) nanoparticles coated in chondrocyte membranes (CM-NPs) were preferentially taken up by rat chondrocytes ex vivo compared with uncoated nanoparticles. Internalization of the CM-NPs was mediated primarily by E-cadherin, clathrin-mediated endocytosis, and micropinocytosis. These CM-NPs adhered to the cartilage ECM in rat knee joints in vivo and penetrated deeply into the cartilage matrix with a residence time of more than 34 days. Simulated synovial fluid clearance studies showed that CM-NPs loaded with a Wnt pathway inhibitor, adavivint (CM-NPs-Ada), delayed the catabolic metabolism of rat and human chondrocytes and cartilage explants under inflammatory conditions. In a surgical model of rat OA, drug-loaded CM-NPs effectively restored gait, attenuated periarticular bone remodeling, and provided chondroprotection against cartilage degeneration. OA progression was also mitigated by CM-NPs-Ada in a canine model of anterior cruciate ligament transection. These results demonstrate the feasibility of using chondrocyte membrane-coated nanoparticles to improve the pharmacokinetics and efficacy of anti-OA drugs.

Background: Heavy metals have been reported to affect liver function. However, there is currently little and inconsistent knowledge about the effects of combined and individual urinary metals on specific parameters of liver function in the general population. Therefore, this study aimed to investigate their associations., Methods: This study involved 807 general population from the China National Human Biomonitoring of Zhejiang Province 2017-2018. Concentrations of urinary metals, including Chromium (Cr), Cobalt (Co), Nickle (Ni), Arsenic (As), Selenium (Se), Molybdenum (Mo), Cadmium (Cd), Thallium (Tl) and Lead (Pb) were measured. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), direct bilirubin (DBIL), total bilirubin (TBIL) as liver function biomarkers. Multivariable linear regression and weighted quantile sum (WQS) regression were employed to explore the associations of urinary metals with liver function biomarkers. Subgroup analysis stratified by gender and age, excluding smokers and drinkers for sensitivity analysis., Results: Both statistical models indicated that urinary metals were positively associated with ALT and AST, while negatively with TP, ALB, DBIL and TBIL. In the WQS analysis, each quartile increase in the ln-transformed levels of metal mixtures was associated with 4.11 IU/L (95% CI: 1.07, 7.15) higher ALT and 3.00 IU/L (95% CI: 1.75, 4.25) higher AST, as well as, with 0.67 g/L (95% CI: 1.24, -0.11) lower TP, 0.74 g/L (95% CI: 1.09, -0.39) lower ALB, 0.38 μmol/L (95% CI: 0.67, -0.09) lower DBIL, and 1.56 μmol/L (95% CI: 2.22, -0.90) lower TBIL. The association between urinary metals and ALT was primarily driven by Cd (55.8%), Cr contributed the most to the association with AST (20.2%) and TBIL (45.2%), while the association with TP was primarily driven by Ni (38.2%), the association with ALB was primarily driven by As (32.8%), and the association with DBIL was primarily driven by Pb (30.9%). The associations between urinary metals and liver function might differ by sex and age., Conclusion: Urinary metals were significantly associated with liver function parameters. Further studies are required to clarify the relationship between heavy metals and liver function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Peanut is an important oil crop worldwide. Peanut web blotch is a fungal disease that often occurs at the same time as other leaf spot diseases, resulting in substantial leaf drop, which seriously affects the peanut yield and quality. However, the molecular mechanism underlying peanut resistance to web blotch is unknown., Results: The cytological examination revealed no differences in the conidium germination rate between the web blotch-resistant variety ZH and the web blotch-susceptible variety PI at 12-48 hpi. The appressorium formation rate was significantly higher for PI than for ZH at 24 hpi. The papilla formation rate at 36 hpi and the hypersensitive response rate at 60 and 84 hpi were significantly higher for ZH than for PI. We also compared the transcriptional profiles of web blotch-infected ZH and PI plants at 0, 12, 24, 36, 48, 60, and 84 hpi using an RNA-seq technique. There were more differentially expressed genes (DEGs) in ZH and PI at 12, 36, 60, and 84 hpi than at 24 and 48 hpi. Moreover, there were more DEGs in PI than in ZH at each time-point. The analysis of metabolic pathways indicated that pantothenate and CoA biosynthesis; monobactam biosynthesis; cutin, suberine and wax biosynthesis; and ether lipid metabolism are specific to the active defense of ZH against YY187, whereas porphyrin metabolism as well as taurine and hypotaurine metabolism are pathways specifically involved in the passive defense of ZH against YY187. In the protein-protein interaction (PPI) network, most of the interacting proteins were serine acetyltransferases and cysteine synthases, which are involved in the cysteine synthesis pathway. The qRT-PCR data confirmed the reliability of the transcriptome analysis., Conclusion: On the basis of the PPI network for the significantly enriched genes in the pathways which were specifically enriched at different time points in ZH, we hypothesize that serine acetyltransferases and cysteine synthases are crucial for the cysteine-related resistance of peanut to web blotch. The study results provide reference material for future research on the mechanism mediating peanut web blotch resistance., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Cancer vaccines are designed to motivate antigen-specific immune responses and facilitate tumor regression with minimal side effects. To fully exert the potential of vaccines, rationally designed formulations that effectively deliver antigens and trigger potent immune reactions are urgently needed. This study demonstrates a simple and controllable vaccine-developing strategy that assembles tumor antigens into bacterial outer membrane vesicles (OMVs), natural delivery vehicles with intrinsic immune adjuvant properties, via electrostatic interaction. This OMV-delivered vaccine (OMVax) stimulated both innate and adaptive immune responses, leading to enhanced metastasis inhibition and prolonged survival of tumor-bearing mice. Moreover, the influence of different surface charged OMVax on antitumor immunity activation is investigated and declined immune response activation occurred with increased positive surface charge. Together, these findings suggest a simple vaccine formulation that can be enhanced by optimizing the surface charges of vaccine formulations., (© 2023 Wiley-VCH GmbH.)

Population and genotype data are essential for genetic mapping. The multi-parent advanced generation intercross (MAGIC) population is a permanent mapping population used for precisely mapping quantitative trait loci. Moreover, genotyping-by-target sequencing (GBTS) is a robust high-throughput genotyping technology characterized by its low cost, flexibility, and limited requirements for information management and support. In this study, an 8-way MAGIC population was constructed using eight elite founder lines. In addition, GenoBaits Peanut 40K was developed and utilized for the constructed MAGIC population. A subset (297 lines) of the MAGIC population at the S2 stage was genotyped using GenoBaits Peanut 40K. Furthermore, these lines and the eight parents were analyzed in terms of pod length, width, area, and perimeter. A total of 27 single nucleotide polymorphisms (SNPs) were revealed to be significantly associated with peanut pod size-related traits according to a genome-wide association study. The GenoBaits Peanut 40K provided herein and the constructed MAGIC population will be applicable for future research to identify the key genes responsible for important peanut traits., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01417-w., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2023.)

Manipulating the tumor immune contexture towards a more active state can result in better therapeutic outcomes. Here we describe an easily accessible bacterial biomineralization-generated immunomodulator, which we name Ausome (Au + [exo]some). Ausome comprises a gold nanoparticle core covered by bacterial components; the former affords an inducible hyperthermia effect, while the latter mobilizes diverse immune responses. Multiple pattern recognition receptors actively participate in Ausome-initiated immune responses, which lead to the release of a broad spectrum of pro-inflammatory cytokines and the activation of effector immune cells. Upon laser irradiation, tumor-accumulated Ausome elicits a hyperthermic response, which improves tissue blood perfusion and contributes to enhanced infiltration of immunostimulatory modules, including cytokines and effector lymphocytes. This immune-modulating strategy mediated by Ausome ultimately brings about a comprehensive immune reaction and selectively amplifies the effects of local antitumor immunity, enhancing the efficacy of well-established chemo- or immuno-therapies in preclinical cancer models in female mice., (© 2023. Springer Nature Limited.)

Scope: Adequate intake of whole grain foods is beneficial to type 2 diabetes mellitus (T2DM). Whether the preventive effects are related with metabolism of branched-chain amino acids (BCAAs) is unclear. The study aims to evaluate the effects of germinated brown rice (GBR) intervention on BCAAs metabolism in T2DM patients., Methods and Results: In this randomized controlled trial, subjects with T2DM are instructed to consume 100 g day -1 GBR (GBR group, n=42) or equal staple food (Control group, n=25) for 3 months. Food frequency questionnaires (FFQ) and serum samples are collected before and after the intervention. In the GBR group, fasting blood glucose (FBG), fasting insulin (FINS), and serum BCAAs are decreased, and islet function is improved (p<0.05). Logistic regression analysis showed that FBG (odds ratios [OR]: 1.55, 95% confidence interval [CI]: 1.01-1.84) and energy (OR: 1.21, 95% CI: 1.09-1.30) are positively associated with serum total BCAAs level, while FINS is negatively associated (OR: 0.20, 95% CI: 0.04-0.88). Simultaneously, the key enzymes of BCAAs decomposition, which promotes glycolysis by activating pyruvate dehydrogenase (PDH), are significantly increased., Conclusion: GBR improves the indicators of T2DM patients, and the underlying mechanisms include improving insulin resistance and accelerating catabolism of BCAAs., (© 2023 Wiley-VCH GmbH.)

Epidemic-related information and resources have proven to have a significant impact on the spread of the epidemic during the Corona Virus Disease 2019 (COVID-19) pandemic. The various orientation role of information has different effects on the epidemic spreading process, which will affect the individual' awareness of resources allocation and epidemic spreading scale. Based on this, a three-layer network is established to describe the dynamic coevolution process among information dissemination, resource allocation, and epidemic spreading. In order to analyze dynamic coevolution process, the microscopic Markov chain (MMC) theory is used. Then, the threshold of epidemic spreading is deduced. Our results indicated that the official information orientation intensity inhibits the epidemics spreading, while rumor orientation intensity promotes epidemic spreading. At the same time, the efficiency of resource utilization restrains the expansion of the infection scale. The two kinds of information are combined with resources respectively. Official information will enhance the inhibitory effect of resources epidemics spreading, while rumor will do the opposite., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Here we present a protocol for the construction and use of two types of nanocarrier based on bacterial membrane materials for cancer vaccine delivery. Cancer vaccines induce tumor regression through triggering the specific T-cell responses against tumor neoantigens, a process that can be enhanced by nanocarrier delivery. Inspired by the body's natural immune defenses against bacterial invasion, we have developed two different types of nanocarrier based on bacterial membrane materials, which employ genetically engineered outer-membrane vesicles (OMVs), or hybrid membrane vesicles containing bacterial cytoplasmic membrane, respectively. The OMV-based nanocarriers can rapidly display different tumor antigens through the surface modified Plug-and-Display system, suitable for customized cancer vaccines when the tumor neoantigens can be identified. The hybrid membrane-based nanocarriers are prepared through fusion of the bacterial cytoplasmic membrane and the primary tumor cell membrane from surgically removed tumor tissues, possessing unique advantages as personalized cancer vaccines when the neoantigens are not readily available. Compared with chemically synthesized nanocarriers such as liposomes and polymer without intrinsic adjuvant properties, owing to the large amounts of pathogen-associated molecular patterns, the two nanocarriers can activate the antigen-presenting cells while delivering multiple antigens, thus inducing effective antigen presentation and robust adaptive immune activation. Excluding bacterial culture and tumor tissue collection, the preparation of OMV- and hybrid membrane-based nanocarriers takes ~8 h and 10 h for tumor vaccine construction, respectively. We also detail how to use these nanocarriers to create cancer nanovaccines and evaluate their immunostimulatory and antitumor effects., (© 2022. Springer Nature Limited.)

Pod size is one of the most important agronomic features of peanuts, which directly affects peanut yield. Studies on the regulation mechanism underpinning pod size in cultivated peanuts remain hitherto limited compared to model plant systems. To better understand the molecular elements that underpin peanut pod development, we conducted a comprehensive analysis of chronological transcriptomics during pod development in four peanut accessions with similar genetic backgrounds, but varying pod sizes. Several plant transcription factors, phytohormones, and the mitogen-activated protein kinase (MAPK) signaling pathways were significantly enriched among differentially expressed genes (DEGs) at five consecutive developmental stages, revealing an eclectic range of candidate genes, including PNC , YUC , and IAA that regulate auxin synthesis and metabolism, CYCD and CYCU that regulate cell differentiation and proliferation, and GASA that regulates seed size and pod elongation via gibberellin pathway. It is plausible that MPK3 promotes integument cell division and regulates mitotic activity through phosphorylation, and the interactions between these genes form a network of molecular pathways that affect peanut pod size. Furthermore, two variant sites, GCP4 and RPPL1 , were identified which are stable at the QTL interval for seed size attributes and function in plant cell tissue microtubule nucleation. These findings may facilitate the identification of candidate genes that regulate pod size and impart yield improvement in cultivated peanuts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Sun, Qi, Tian, Wang, Zhao, Wang, Wu, Shi, Liu, Dong, Huang, Zheng and Zhang.)

Despite the fact that transcatheter cardiovascular interventions are increasingly prevalent nowadays, friction damage caused by mechanical interaction between blood vessel and cardiovascular catheter limit their therapeutic utility. Based on dopamine-modified hyaluronic (HA-DN) acid and chitosan (CHI), a layer-by-layer lubricating coating for cardiovascular catheters was designed and assessed in this work. Results showed that the CHI/HA-DN composite coatings became more hydrophilic as the deposition layers were increased. The (CHI/HA-DN) 8 assembly effectively reduced the coefficient of friction (COF) and related frictional energy dissipation. Besides, the fluorescent intensity, number of nucleus, SEM morphology and histological slices after friction experiment demonstrated that the (CHI/HA-DN) 8 coating can protect the aorta from mechanical injury related to the control group. In conclusion, the CHI/HA-DN assembly can provide an alternative selection for low-damage lubricating cardiovascular catheter., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Treating and utilizing heavy metal enriched plants have become growing problems. In this work, a series of composite foams were made from the powder of Cadmium-rich plant, polyacrylonitrile (PAN) and polyurethane (PU). Test results indicated that the addition of plant powder can not only increase the specific surface area, but also improve the apparent density and thermal stability of the foams. Besides, compared with the foam without plant powder, the powder-added foams exhibited a decreasing trend for thermal conductivity, and the minimum was 0.048 w/(m·k), which indicated that the addition of plant powder can help to enhance the thermal insulation of composite foam. More importantly, the results of leaching experiment showed that the leaching rate of heavy metal cadmium in the composite foam with 50% plant powder content was as low as 0.14% after being immersed in the acidic (pH = 3) solution for 5 days, which implies that the foam materials are very safe. This study provides a new way to realize high value-added resource utilization of heavy metal-enriched plants.

Manufacturing facile and low-cost wound dressings that simultaneously meet the needs of the entire repair process remains the major challenge of effective wound healing. Herein, a series of curdlan-tannic acid hybrid hydrogels were successfully fabricated through the annealing technique. Notedly, when the mixing weigh ratio was 1:1, the hydrogel exhibited excellent physicochemical properties, including swellability, degradability, water retention, porosity, and rheology. Additionally, the hydrogel did not display significant cytotoxicity to fibroblasts and the hemolysis rate at 12 h was 3%. Interestingly, the hybrid hydrogel showed multifunctional properties, including remarkable antioxidant, antibacterial, and rapid hemostasis effects reduce blood loss by 0.35 g, that were achieved through the temperature-dependent release of tannic acid. Moreover, a full-thickness skin defect animal model was used to verify that the multifunctional hydrogel could accelerate wound healing in vivo. These results suggest that this hybrid hydrogel is a promising candidate for the clinical treatment of full-thickness wounds., (Copyright © 2021. Published by Elsevier Ltd.)

Blockage and infection are common in hospitals, especially with long-term indwelling catheters, due to bacterial adhesion, colonization, and other reasons. A drug-sustained-release antibacterial coating for urinary catheters was described in this paper. Chlorhexidine (CHX) and triclosan (TCS) were encapsulated in poly(lactic-co-glycolic acid) microspheres and mixed with a modified chitosan hydrogel deposited on the surface of silicone rubber. The results showed that drugs can be released continuously more than 35 days. Catechol-modified chitosan (Chi-C) hydrogel was successful synthesized according to FT-IR and UV spectrophotometry, as well as 1 H NMR. Furthermore, the coating with CHX and TCS presented stable antibacterial ability compared to the other groups. The results of CCK-8 revealed that the coating was cytotoxic-free and had a wide range of applications. The findings could provide a new drug sustained-release system and hydrogel-microsphere assembly for urinary catheters. HighlightsThe microspheres presented a sustained release more than 40 days with a remarkable initial burst release.The microspheres/catechol-modified chitosan (Chi-C)/silicon rubber system emerged stable binding ability in liquid environment more than 14 days.The Chi-C/chlorhexidine (CHX)+triclosan (TCS) microspheres system presented better antimicrobial property for entire experiment period.The coated samples showed no significant difference for relative growth rate (RGR) compared to different groups.

Iron is an essential element for cell proliferation and homeostasis by engaging in cell metabolism including DNA synthesis, cell cycle, and redox cycling; however, iron overload could contribute to tumor initiation, proliferation, metastasis, and angiogenesis. Therefore, manipulating iron metabolisms, such as using iron chelators, transferrin receptor 1 (TFR1) Abs, and cytotoxic ligands conjugated to transferrin, has become a considerable strategy for cancer therapy. However, there remain major limitations for potential translation to the clinic based on the regulation of iron metabolism in cancer treatment. Nanotechnology has made great advances for cancer treatment by improving the therapeutic potential and lowering the side-effects of the proved drugs and those under various stages of development. Early studies that combined nanotechnology with therapeutic means for the regulation of iron metabolism have shown certain promise for developing specific treatment options based on the intervention of cancer iron acquisition, transportation, and utilization. In this review, we summarize the current understanding of iron metabolism involved in cancer and review the recent advances in iron-regulatory nanotherapeutics for improved cancer therapy. We also envision the future development of nanotherapeutics for improved treatment for certain types of cancers., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Nanocarriers with intrinsic immune adjuvant properties can activate the innate immune system while delivering tumor antigen, thus efficiently facilitating antitumor adaptive immunity. Bacteria-derived outer membrane vesicles (OMVs) are an excellent candidate due to their abundance of pathogen associated molecular patterns. However, during the uptake of OMVs by dendritic cells (DCs), the interaction between lipopolysaccharide and toll-like receptor 4 induces rapid DC maturation and uptake blockage, a phenomenon we refer to as "maturation-induced uptake obstruction" (MUO). Herein we decorated OMV with the DC-targeting αDEC205 antibody (OMV-DEC), which endowed the nanovaccine with an uptake mechanism termed as "not restricted to maturation via antibody modifying" (Normandy), thereby overcoming the MUO phenomenon. We also proved the applicability of this nanovaccine in identifying the human tumor neoantigens through rapid antigen display. In summary, this engineered OMV represents a powerful nanocarrier for personalized cancer vaccines, and this antibody modification strategy provides a reference to remodel the DC uptake pattern in nanocarrier design., Competing Interests: G.N., X.Z., Y.Z. and J.L. are inventors on a filed provisional application China patent no. 202110129743.9 (A general vaccine vector based on bacterial outer membrane vesicles) submitted by the National Center for Nanoscience and Technology that covers the potential diagnostic and therapeutic uses of the vaccine for cancer immunotherapy. The authors declare that they have no other competing interests., (© 2021 The Authors. Publishing Services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

(1) Background: Bacterial infections have long threatened global public safety; hence, it is significant to continuously develop antibacterial fibers that are closely related to people's daily lives. Berberine hydrochloride is a natural antibacterial agent that has application prospects in the preparation of antibacterial fibers. (2) Methods: This study firstly verified the antibacterial properties of berberine hydrochloride and its possible antibacterial mechanism. Thereafter, berberine hydrochloride was introduced into the self-made melt-spun polyurethane fiber through optimized coating technology. The performance of coating modified polyurethane fiber has been systematically evaluated, including its antibacterial properties, mechanical properties, and surface wettability. (3) Results: Results show that the antibacterial polyurethane fiber with desirable comprehensive properties is expected to be used in the biomedical fields. (4) Conclusions: The research also provides a reference for the development and application of other natural antibacterial ingredients in fiber fields.

Cancer vaccines based on resected tumors from patients have gained great interest as an individualized cancer treatment strategy. However, eliciting a robust therapeutic effect with personalized vaccines remains a challenge because of the weak immunogenicity of autologous tumor antigens. Utilizing exogenous prokaryotic constituents that act as adjuvants to enhance immunogenicity is a promising strategy to overcome this limitation. However, nonspecific stimulation of the immune system may elicit an undesirable immunopathological state. To specifically trigger sufficient antitumor reactivity without notable adverse effects, we developed an antigen and adjuvant codelivery nanoparticle vaccine based on Escherichia coli cytoplasmic membranes (EMs) and tumor cell membranes (TMs) from resected autologous tumor tissue. Introduction of the EM into the hybrid membrane nanoparticle vaccines (HM-NPs) induced dendritic cell maturation, thus activating splenic T cells. HM-NPs showed efficacy in immunogenic CT26 colon and 4T1 breast tumor mouse models and also efficiently induced tumor regression in B16-F10 melanoma and EMT6 breast tumor mouse models. Furthermore, HM-NPs provoked a strong tumor-specific immune response, which not only extended postoperative animal survival but also conferred long-term protection (up to 3 months) against tumor rechallenge in a CT26 colon tumor mouse model. Specific depletion of different immune cell populations revealed that CD8 + T and NK cells were crucial to the vaccine-elicited tumor regression. Individualized autologous tumor antigen vaccines based on effective activation of the innate immune system by bacterial cytoplasmic membranes hold great potential for personalized treatment of postoperative patients with cancer., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Due to their ability to elicit a potent immune reaction with low systemic toxicity, cancer vaccines represent a promising strategy for treating tumors. Considerable effort has been directed toward improving the in vivo efficacy of cancer vaccines, with direct lymph node (LN) targeting being the most promising approach. Here, a click-chemistry-based active LN accumulation system (ALAS) is developed by surface modification of lymphatic endothelial cells with an azide group, which provide targets for dibenzocyclooctyne (DBCO)-modified liposomes, to improve the delivery of encapsulated antigen and adjuvant to LNs. When loading with OVA 257-264 peptide and poly(I:C), the formulation elicits an enhanced CD8 + T cell response in vivo, resulting in a much more efficient therapeutic effect and prolonged median survival of mice. Compared to treatment with DBCO-conjugated liposomes (DL)-Ag/Ad without the azide targeting, the percent survival of ALAS-vaccine-treated mice improves by 100% over 60 days. Altogether, the findings indicate that the novel ALAS approach is a powerful strategy to deliver vaccine components to LNs for enhanced antitumor immunity., (© 2021 Wiley-VCH GmbH.)

An effective tumor vaccine vector that can rapidly display neoantigens is urgently needed. Outer membrane vesicles (OMVs) can strongly activate the innate immune system and are qualified as immunoadjuvants. Here, we describe a versatile OMV-based vaccine platform to elicit a specific anti-tumor immune response via specifically presenting antigens onto OMV surface. We first display tumor antigens on the OMVs surface by fusing with ClyA protein, and then simplify the antigen display process by employing a Plug-and-Display system comprising the tag/catcher protein pairs. OMVs decorated with different protein catchers can simultaneously display multiple, distinct tumor antigens to elicit a synergistic antitumour immune response. In addition, the bioengineered OMVs loaded with different tumor antigens can abrogate lung melanoma metastasis and inhibit subcutaneous colorectal cancer growth. The ability of the bioengineered OMV-based platform to rapidly and simultaneously display antigens may facilitate the development of these agents for personalized tumour vaccines.

Messenger RNA (mRNA) vaccine is a promising candidate in cancer immunotherapy as it can encode tumor-associated antigens with an excellent safety profile. Unfortunately, the inherent instability of RNA and translational efficiency are major limitations of RNA vaccine. Here, we report an injectable hydrogel formed with graphene oxide (GO) and polyethylenimine (PEI), which can generate mRNA (ovalbumin, a model antigen) and adjuvants (R848)-laden nanovaccines for at least 30 days after subcutaneous injection. The released nanovaccines can protect the mRNA from degradation and confer targeted delivering capacity to lymph nodes. The data show that this transformable hydrogel can significantly increase the number of antigen-specific CD8 + T cells and subsequently inhibit the tumor growth with only one treatment. Meanwhile, this hydrogel can generate an antigen specific antibody in the serum which in turn prevents the occurrence of metastasis. Collectively, these results demonstrate the potential of the PEI-functionalized GO transformable hydrogel for effective cancer immunotherapy.

A major challenge in cancer vaccine therapy is the efficient delivery of antigens and adjuvants to stimulate a controlled yet robust tumour-specific T-cell response. Here, we describe a structurally well defined DNA nanodevice vaccine generated by precisely assembling two types of molecular adjuvants and an antigen peptide within the inner cavity of a tubular DNA nanostructure that can be activated in the subcellular environment to trigger T-cell activation and cancer cytotoxicity. The integration of low pH-responsive DNA 'locking strands' outside the nanostructures enables the opening of the vaccine in lysosomes in antigen-presenting cells, exposing adjuvants and antigens to activate a strong immune response. The DNA nanodevice vaccine elicited a potent antigen-specific T-cell response, with subsequent tumour regression in mouse cancer models. Nanodevice vaccination generated long-term T-cell responses that potently protected the mice against tumour rechallenge.

Objective: Salivagram is one of the imaging modalities to detect pulmonary aspiration in children. This study aims to optimize the classification of pulmonary aspiration detected by salivagram with a semi-quantitative analytical method., Methods: This is a retrospective study involving 737 patients (471 males, 266 females; aged 1 month to 8 years; mean age 5.3 months, median age 3.0 months old) with suspected pulmonary aspiration, who had salivagram done between January 2018 and June 2019. Positive cases were divided into 10 groups (Grade 1, R2, L2, R2L2, R3, L3, R3L2, R2L3, R3L3, and 4) according to the scintigraphic findings. Aspiration index was determined as the ratio of the count in the respiratory tract to the total count in the image field of view and compared among different groups using the receiver operating characteristics (ROC) curve analysis., Results: A total of 180 cases had positive scintigraphic findings of various grades of aspiration (24.4%, 180/737). There is a high consistency among the two independent nuclear medicine physicians involved in the study, in determining both the disease gradings (κ = 0.919;95% CI: 0.915-0.923) and aspiration index (ICC = 0.994;95% CI: 0.993-0.996). There is no significant difference (p > 0.05) in aspiration index among the gradings in "mild" group (grade 1, R2, L2, L2R2), and "moderate" group (grade R3, R3L2, R3L3). After dividing the different grades into "mild", "moderate" and "severe" groups, the aspiration index of "mild" group is 4.40 ± 2.01, that of "moderate" group is 16.43 ± 8.20, and that of "severe" group is 46.94 ± 14.81. Difference in groups was statistically significant (p < 0.0001). In ROC curve analysis, AUC of "mild" and "moderate" groups is 0.970 and that of "moderate" and "severe" groups is 0.943; the cut-off value with highest diagnostic efficiency is 6.75 between "mild" and "moderate" groups and 38.00 between "moderate" and "severe" groups., Conclusions: We introduced a semi-quantitative analytical method in pulmonary aspiration on salivagram, to optimize and supplement to the current classification of pulmonary aspiration.

Sintered microsphere-based scaffolds provide a porous structure and high-resolution spatial organization control, show great potential for bone regeneration, mainly from biodegradable biomaterials including poly(lactic-glycolic acid) (PLGA). However, acidic monomer regeneration, mainly from biodegradable biomaterials including poly(lactic-glycolic acid) (PLGA). However, acidic monomers generated by PLGA degradation tend to cause tissue inflammation, which is the central issue of PLGA-based bone regeneration scaffolds development. In this work, calcium carbonate (CC)/hexagonal mesoporous silica (HMS)/PLGA sintered microsphere-based scaffolds were developed. The scaffolds possessed a three-dimensional (3D) network structure and 30-40% porosity. The degradation results indicated that CC/HMS/PLGA scaffolds could compensate for pH increased caused by PLGA acidic byproducts effectively. Degradation results showed that CC/HMS/PLGA scaffold could effectively compensate for the pH increase caused by PLGA acidic by-products. Composite CC additives can induce the increase of adhesive proteins in the environment, which is conducive to the adhesion of cells to scaffolds. Mesenchymal stem cells (MSCs) proliferation and osteogenic differentiation were evaluated by CCK-8 assay, alkaline phosphatase (ALP) activity, ALP staining, and Alizarin Red staining. The results showed that compared with HMS/PLGA scaffolds, the proliferation of MSCs cultured with CC/HMS/PLGA scaffolds was enhanced. When cultured on the CC/HMS/PLGA scaffolds, MSCs also showed significantly enhanced ALP activity and higher calcium secretion compared with the HMS/PLGA scaffolds. CC/HMS/PLGA sintered microsphere-based scaffolds provides an attractive strategy for bone repair and regeneration with better performance., Competing Interests: The authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Natural, extracellular membrane vesicles secreted by Gram-negative bacteria, outer membrane vesicles (OMVs), contain numerous pathogen-associated molecular patterns which can activate systemic immune responses. Previous studies have shown that OMVs induce strong IFN-γ- and T cell-mediated anti-tumor effects in mice. However, IFN-γ is known to upregulate immunosuppressive factors in the tumor microenvironment, especially the immune checkpoint programmed death 1 ligand 1 (PD-L1), which may hamper T cell function and limit immunotherapeutic effectiveness. Here, we report the development of genetically engineered OMVs whose surface has been modified by insertion of the ectodomain of programmed death 1 (PD1). This genetic modification does not affect the ability of OMVs to trigger immune activation. More importantly, the engineered OMV-PD1 can bind to PD-L1 on the tumor cell surface and facilitate its internalization and reduction, thereby protecting T cells from the PD1/PD-L1 immune inhibitory axis. Through the combined effects of immune activation and checkpoint suppression, the engineered OMVs drive the accumulation of effector T cells in the tumor, which, in turn, leads to a greater impairment of tumor growth, compared with not only native OMVs but also the commonly used PD-L1 antibody. In conclusion, this work demonstrates the potential of bioengineered OMVs as effective immunotherapeutic agents that can comprehensively regulate the tumor immune microenvironment to effect markedly increased anti-tumor efficacy.

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and liver injury, and is the leading cause of chronic liver disease worldwide. There is an urgent need to develop novel pathophysiology-oriented therapy in human. Rapamycin (RAPA) has been recognized as a promising drug for alleviating hepatic steatosis on NAFLD, but the poorly water-soluble properties and side effects of RAPA limit their clinical use. In this study, we aimed to investigate the in vitro and in vivo therapeutic efficacy of biodegradable mPEG-PLGA polymers loaded with RAPA (NP-RAPA) on NAFLD. NP-RAPA were prepared by a green process using an emulsion/solvent evaporation method, the therapeutic efficacy on NAFLD were investigated on HepG2 cells incubated with oleic acid (OA) and in the livers of mice with NAFLD induced by high-fat diet (HFD). Compared with free RAPA, NP-RAPA significantly reduced lipid accumulation in HepG2 cells, and obviously ameliorated hepatic steatosis and liver injury in mice though enhancing the therapeutic efficacy of RAPA through reducing SREBP-1c-dependent de novo lipogenesis (DNL) and promoting PPARα-mediated fatty acid oxidation. This study suggests that mPEG-PLGA can be used as the potential therapeutic strategy and novel drug delivery for improving the efficacy of rapamycin for treatment of NAFLD., (Copyright © 2020 Zhao, Zhu, Zhou, Feng and Chen.)

Engineered nanoparticles could trigger inflammatory responses and potentiate a desired innate immune response for efficient immunotherapy. Here we report size-dependent activation of innate immune signaling pathways by gold (Au) nanoparticles. The ultrasmall-size (<10 nm) Au nanoparticles preferentially activate the NLRP3 inflammasome for Caspase-1 maturation and interleukin-1β production, while the larger-size Au nanoparticles (>10 nm) trigger the NF-κB signaling pathway. Ultrasmall (4.5 nm) Au nanoparticles (Au4.5) activate the NLRP3 inflammasome through directly penetrating into cell cytoplasm to promote robust ROS production and target autophagy protein-LC3 (microtubule-associated protein 1-light chain 3) for proteasomal degradation in an endocytic/phagocytic-independent manner. LC3-dependent autophagy is required for inhibiting NLRP3 inflammasome activation and plays a critical role in the negative control of inflammasome activation. Au4.5 nanoparticles promote the degradation of LC3, thus relieving the LC3-mediated inhibition of the NLRP3 inflammasome. Finally, we show that Au4.5 nanoparticles could function as vaccine adjuvants to markedly enhance ovalbumin (OVA)-specific antibody production in an NLRP3-dependent pattern. Our findings have provided molecular insights into size-dependent innate immune signaling activation by cell-penetrating nanoparticles and identified LC3 as a potential regulatory target for efficient immunotherapy.

The limited efficacy of single-agent immune checkpoint inhibitors in treating tumors has prompted investigations on their combination partners. Here, a tumor-homing indoleamine 2,3-dioxygenase (IDO) nanoinhibitor is reported to selectively inhibit immunosuppressive IDO pathway in the tumor microenvironment. It is self-assembled from a modularly designed peptide-drug conjugate containing a hydrophilic targeting motif (arginyl-glycyl-aspartic acid; RGD), two protonatable histidines, and an ester bond-linked hydrophobic IDO inhibitor, which exhibits pH-responsive disassembly and esterase-catalyzed drug release. Markedly, it achieved potent and persistent inhibition of intratumoral IDO activity with a reduced systemic toxicity, which greatly enhanced the therapeutic efficacy of programmed cell death-ligand 1 blockade  in vivo . Overall, this study provides a promising paradigm of combinatorial normalization immunotherapy by exploiting a targeted IDO nanoinhibitor to augment the antitumor immunity of checkpoint inhibitors.

The development of degradable polymer scaffolds is a key issue in bone regeneration. Poly(D, L-lactide) (PDLLA) and its derivatives have usually been applied to the construction of degradable scaffolds, but these scaffolds had problems with acidic degradation products and quick loss of mechanic strength during the later degradation, which usually led to scaffold collapse and cavity formation because of the slower rate of bone regeneration. In the present paper, a polysaccharide derivative, agarose acetate (AGA), was synthesized and a novel porous AGA scaffold was successfully developed through a salt-leaching process. The AGA scaffold had over 90% porosity without swelling in water, and compared to collapse and acidic products of PDLLA scaffold during degradation, the AGA scaffold maintained a stable morphology and a nearly neutral pH value over 18 months' degradation in PBS. A bone mesenchymal stem cells (BMSCs) adhesion and proliferation experiment showed that more cells adhered to the AGA scaffold than to the PDLLA scaffold. A subcutaneous implant test showed that the AGA scaffold slowly degraded and did not cause an inflammatory response surrounding the implantation lesion site. AGA scaffold was implanted into femur defects in New Zealand white rabbits to test its in vivo performance. Results indicated that the AGA scaffold accelerated the process of bone regeneration compared to the PDLLA group and, with time, new bone was formed from the margin toward the center of the scaffolds, and the scaffold left in place retained its porous structure without collapsing. Meanwhile, the AGA scaffold showed a low degradation rate and kept its shape during the in vivo degradation compared to the PDLLA scaffold. This performance could have the benefit of integrated regenerative bone being formed instead of cavities due to the quickly degraded scaffold disappearing. These results demonstrate that the AGA scaffold has significant potential in bone regeneration applications.

Objective: Salivagrams are commonly used for detecting pulmonary aspiration. However, conventional dynamic imaging is relatively time-consuming and could be difficult to perform in children with poor compliance. We analyzed the characteristics of conventional dynamic imaging to obtain a simple protocol suitable for use in children., Methods: We conducted a retrospective analysis of salivagram data from 1163 patients (783 males, 380 females; age, 1 month to 9.0 years; mean age, 5.7 months) obtained in the past 4.5 years (January 2014 to June 2018). The various timepoint images were used for diagnosis. The positivity rate, missed diagnosis rate, and sensitivity were calculated and compared., Results: Dynamic imaging revealed 353 cases of pulmonary aspiration (248 males, 105 females; age, 1 month to 4.5 years; mean age, 6.2 months). The positivity rate was 30.4% (353/1163), and 95.8% (338/353) of patients presented with continuous positive images after pulmonary aspiration. Only 4.2% (15/353) of positive cases showed clearance of pulmonary aspiration. The positivity rates were 11.8%, 18.2%, 21.9%, 25.0%, 27.0%, and 29.2% at 5, 10, 15, 20, 25, and 30 minutes, respectively. About 4.2% (15/353) of positive cases on earlier images showed clearance of pulmonary aspiration on later images, which indicate both early 15-minute and later 30-minute images were necessary., Conclusions: Two static images acquired at 15 and 30 minutes might be an effective alternative to conventional salivagram, which mandates dynamic imaging.

Smart wet-spun fibers for highly programmable release of therapeutic drug have been rarely reported. Herein, thermalresponsive composite fibers were successfully prepared by core-sheath wet-spinning technology in present study. They consisted of a model drug of natural antibacterial berberine chloride hydrate (BCH) and a drug carrier of temperature responsive shape memory polyurethane (SMPU). The obtained composite fibers featured with well-controlled microscopic morphologies, exhibiting significantly enhanced thermal stability and superb mechanical properties. In vitro drug release test and corresponding release kinetics study were performed for investigation of BCH's release behavior. Results demonstrated that the release behaviors of BCH from the core-sheath fibers were pH-dependent, influenced by both diffusion from pore channels and the solubility of BCH in the release mediums, and BCH imbedded only in core part showed a longer release period compared with that in both core and sheath parts of the composite fibers. More importantly, the release rate of BCH can be simply controlled by changing the initial shapes of fibers through stretching and fixation of the stretched deformations. Furthermore, the antibacterial durability of the smart composites fibers was demonstrated and tracked according to the growth inhibition against both negative E. coli and positive S. aureus bacteria strains. All these results suggest that the developed composite fibers can be promising candidates as smart drug delivery vehicles for highly adjustable doses of target drugs towards practical applications.

Rapidly growing cancer cells exhibit a strong dependence on iron for their survival. Thus, iron-removing drugs, iron chelators, have potential applications in cancer treatment. Deferoxamine (DFO) is an efficient iron chelator, but its short circulation half-life and ability to induce hypoxia-inducible factor 1α (HIF1α) overexpression restricts its use as an antitumor agent. In the present study, we first found that a pattern of iron-related protein expression favoring higher intracellular iron closely correlates with shorter overall and relapse-free survival in pancreatic cancer patients. We subsequently found that a combination of DFO and the HIF1α inhibitor, lificiguat (also named YC1), significantly enhanced the antitumor efficacy of DFO in vitro. We then employed transferrin receptor 1 (TFR1) targeting liposomes to codeliver DFO and YC1 to pancreatic tumors in a mouse model. The encapsulation of DFO prolonged its circulation time, improved its accumulation in tumor tissues via the enhanced permeability and retention (EPR) effect, and facilitated efficient uptake by cancer cells, which express high level of TFR1. After entering the tumor cells, the encapsulated DFO and YC1 were released to elicit a synergistic antitumor effect in subcutaneous and orthotopic pancreatic cancer xenografts. In summary, our work overcame two major obstacles in DFO-based cancer treatment through a simple liposome-based drug delivery system. This nanoencapsulation and targeting paradigm lays the foundation for future application of iron chelation in cancer therapy.

Recent advances in cancer immunotherapy have exploited the efficient potential of natural killer (NK) cells to kill tumor cells through antibody-dependent cell-mediated cytotoxicity (ADCC). However, this therapeutic strategy is seriously limited by tumor antigen heterogeneity since antibodies can only recognize specific antigens. In this work, modified antibodies or their Fc fragments that can target solid tumors without the necessity of specific antigen presentation on tumors are developed. Briefly, Fc fragments or therapeutic monoclonal antibodies are conjugated with the N-terminus of pH low insertion peptide so that they will selectively assemble onto the membrane of solid tumor cells via the conformational transformation of the peptide by responding to the acidic tumor microenvironment. The inserted Fc fragments or antibodies can efficiently activate NK cells, initiating ADCC and killing multiple types of tumor cells, including antigen-negative cancer cells. In vivo therapeutic results also exhibit significant efficacy on both primary solid tumors and tumor metastasis. These modified Fc fragments and antibodies present strong potential to overcome the limitation of tumor antigen heterogeneity, broadening the applications of NK cell immunotherapy on solid tumor treatment., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In the present paper, agarose acetate (AGA) nanofibrous membranes containing different weight percentages of β-tricalcium phosphate (β-TCP) were successfully developed through electrospinning. The fibers in the nanofibrous membranes had a rough surface due to the β-TCP particles which were uniformly dispersed within or on the surface of AGA fibers. Rat-bone marrow-derived mesenchymal stem cells (rBMSCs) were cultured on the AGA based nanofibrous membranes while showed a good adhesion and proliferation. It was found that more rBMSCs were differentiated to osteoblast-like cells on the β-TCP containing nanofibrous membranes compared with the single AGA membrane, and more alkaline phosphatase (ALP) and mineralized matrix could be detected when rBMSCs were cultured on the β-TCP containing nanofibrous membranes. The nanofibrous membranes were implanted into Sprague-Dawley (SD) rats for biocompatibility test. Gross examination and histological analysis of the AGA based nanofibrous membranes results showed that there was less inflammatory response. All of experimental results suggested that the AGA based nanofibrous membranes had the great potential application in bone tissue engineering., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Pancreatic ductal adenocarcinoma is characterised by a dense desmoplastic stroma composed of stromal cells and extracellular matrix (ECM). This barrier severely impairs drug delivery and penetration. Activated pancreatic stellate cells (PSCs) play a key role in establishing this unique pathological obstacle, but also offer a potential target for anti-tumour therapy. Here, we construct a tumour microenvironment-responsive nanosystem, based on PEGylated polyethylenimine-coated gold nanoparticles, and utilise it to co-deliver all-trans retinoic acid (ATRA, an inducer of PSC quiescence) and siRNA targeting heat shock protein 47 (HSP47, a collagen-specific molecular chaperone) to re-educate PSCs. The nanosystem simultaneously induces PSC quiescence and inhibits ECM hyperplasia, thereby promoting drug delivery to pancreatic tumours and significantly enhancing the anti-tumour efficacy of chemotherapeutics. Our combination strategy to restore homoeostatic stromal function by targeting activated PSCs represents a promising approach to improving the efficacy of chemotherapy and other therapeutic modalities in a wide range of stroma-rich tumours.

A Meckel's scintigraphy using TcO4 was performed in a 9-year-old boy. The images revealed an elongated abnormal radiotracer accumulation in the right abdomen, which was confirmed as Meckel diverticulum combined with an omphalomesenteric cyst.