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Money has been portrayed by major theorists as an agent of individualism, an instrument of freedom, a currency that removes personal values attached to things, and a generator of avarice. Regardless, the impact of money varies greatly with the cultural turf of the recipient societies. For traditional subsistence economies based on gifting and sharing, surplus perishable resources foraged from the environment carry low costs to the giver compared with the benefits to the receiver. With cash, costs to the giver are usually the same as benefits to the receiver, making sharing expensive and introducing new choices. Using quantitative data on possessions and expenditures collected over a 44-y period from 1974 to 2018 among the Ju/’hoansi (!Kung) in southern Africa, former hunter-gatherers, we look at how individuals spend monetary income, how a partial monetary economy alters traditional norms and institutions (egalitarianism, gifting, and sharing), and how institutions from the past steer change. Results show that gifting declines as cash is spent to increase the well-being of individual families and that gifting and sharing decrease and networks narrow. The sharing of meals and casual gifting hold fast. Substantial material inequalities develop, even between neighbors, but social, gender, and political equalities persist. A strong tradition for individual autonomy combined with monetary income allows individuals to spend their money as they choose, adapt to modern conditions, and pursue new options. However, new challenges are emerging to develop greater community cooperation and build substantial and sustainable economies in the face of such centrifugal forces.

Yee Huang, Li Nan, Chenwen Xiao, Jie Dong, Ke Li, Jvfen Cheng, Quanan Ji, Qiang Wei, Guolian Bao, Yan Liu Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of ChinaCorrespondence: Guolian Bao; Yan Liu, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of China, Email baoguolian@163.com; 35792191@qq.comPurpose: Outer membrane vesicles (OMVs) are spherical nano-sized proteolipids secreted by numerous pathogenic Gram-negative bacteria. Due to the immunostimulatory properties and protective efficacy, OMVs have received increasing attention as a candidate for the vaccine to prevent and treat bacterial infections. However, the immune response remains elusive due to the low structural stability and poor size homogeneity of the vesicles. In this study, OMVs were used to coat self-assembled glycyrrhizic acid nanoparticles (GANs) and obtain a stable OMV vaccine. The immunoprotective effects and anti-infection efficacy were evaluated in vivo and in vitro.Methods: The OMVs were prepared by ultrafiltration method and fused with GAN through mechanical extrusion. The characteristics, including morphology, hydrodynamic size, zeta potential, and stability were evaluated. The in vitro immunological function of GAN-OMV on the macrophages and in vivo immune efficacy and anti-infection effect were examined and compared.Results: The results showed that the GAN-OMV were homogenous with a size of 130 nm and a stable core-shell structure. Micropinocytosis-dependent and clathrin-mediated endocytotic pathways effectively internalized the GAN-OMV into the macrophages and promoted cell proliferation, cytokine secretion, and M1 polarization. Furthermore, subcutaneous GAN-OMV vaccination contributed to significantly higher Borderella bronchiseptica (Bb)-specific antibody production and lymphocyte proliferation. The splenic lymphocytes of mice immunized with GAN-OMVs displayed a higher ratio of CD4+/CD8+ T cells and CD19+ B cells and produced significantly higher levels of Th1/Th2/Th17 cytokines. GAN-OMV also effectively prevented Bb reinfection.Conclusion: In this study, GAN-OMV was developed successfully to stimulate Th1/Th2/Th17 immune responses against Bb and provide a promising strategy for novel vaccine development against the microbial pathogen.Keywords: outer membrane vesicles, glycyrrhizic acid nanoparticle, macrophage, protective immune response, anti-bacterial infection

Background Trichophyton mentagrophyte (TM), a zoonotic pathogen, has been endangering public health due to emerging drug resistance. Although increased attention is paid to this issue, there is very limited research available on drug resistance in TM. In this study, we studied the gene and proteomic changes, morphological changes, cellular fat localization, fat content changes, and biofilm of TM treated with different substances. Results The TM growth curve showed a positive correlation with the concentration of Fenarimol (FE), genistein (GE), clotrimazole (KM), and Miconazole nitrate salt (MK). The morphology of TM cells changed in different degrees after treatment with different substances as observed by TEM and SEM. The results showed that under KM and berberine hydrochloride (BB) treatment, a total of 3305 differentially expressed genes were detected, with the highest number in the KM-treated group (578 up-regulated and 615 down-regulated). A total of 847 proteins and 1850 peptides were identified in TM proteomics. Nile red staining showed that the fat content of TM was significantly higher in the BB-, ethidium bromide- (EB), FE-, KM-, Adriamycin hydrochloride- (YA), and MK-treated group compared to the control group. Results of the biofilm thickness showed that it gradually increased under treatment with specific concentrations of KM or BB, which may be related to the up-regulation of ERG25 and CYP related gene proteins. Conclusions It is suggested that in order to effectively deal with dermatomycosis caused by TM, it is necessary to inhibit the expression of ERG25 and CYP related genes and fat metabolism, which can result in the inhibition of the production of biofilm by the fungus and solve the problem of fungal drug resistance in clinical settings.

Background Rehmannia glutinosa polysaccharide is the main reason that contributes to the immunological function of R. glutinosa. Due to its disadvantages in clinical use, here we designed the PEGylation nano-RGP (pRL) to improve the drug-targeting effect and the immunological function. Our present work aims to establish the optimum condition of preparing the pRL and to investigate its immunological function on macrophages. Methods pRL was prepared by thin film hydration method combined with ultra-sonication technique. And its preparation conditions were optimized with response surface methodology. Also, the lyophilization method was optimized. The characteristics of the pRL were evaluated, including particle size, drug loading, encapsulation efficiency and morphology. The immunological function of pRL on macrophage was investigated through CCK-8 test, ELISA and flow cytometry. Results The lipid-to-cholesterol molar ratio of 8:1, the addition of DSPE-PEG2000 of 9% and the lipid-to-drug ratio of 5.4:1 were the optimum preparation technology for pRL. The encapsulation efficiency (EE) of pRL under this preparation technology was 95.81±1.58%, with a particle size of 31.98 ± 2.6 nm. The lactose-to-lipid ratio (2:1) was the optimal lyophilization method. pRL promoted macrophage proliferation, which is significantly better than that of nano-RGP without PEGylation (RL). pRL-stimulated RAW264.7 cells showed a high secretion of pro-inflammatory cytokines, which is the characteristic indicator of M1 polarization. Enhanced cellular uptake through macropinocytosis-dependent and caveolae-mediated endocytosis was observed in pRL-treated RAW264.7 cells. Conclusion Our study concluded that PEGylation effectively overcame the poor targeting effect of Rehmannia glutinosa polysaccharide (RGP) and significantly improved the immunological profile of its nano-formulation, which suggested that pRL could serve as an immune adjuvant in clinical application.

Graphene oxide quantum dots (GOQDs) have attracted substantial attention in numerous fields due to their unique physicochemical properties. However, their nanotoxicity and potential for use in biomedicine still require further study. In this work, the effects of GOQD and trans- 10-hydroxy-2-decenoic acid (10-HDA) cotreatment on the immune function of macrophages (RAW264.7 cells) were investigated. In particular, LC/MS-based metabolomics was performed to evaluate the effects of GOQDs on the metabolism of LPS-stimulated macrophages. Herein, we fabricated GOQDs with good dispersibility and a uniform size distribution of approximately 7 nm using a polyimide-pyrolyzed carbon film as the working electrode, a high-voltage graphite electrode as the cathode, and H

Outer membrane vesicles (OMVs) are spherical nano-sized proteolipids secreted by numerous pathogenic Gram-negative bacteria. Due to the immunostimulatory properties and protective efficacy, OMVs have received increasing attention as a candidate for the vaccine to prevent and treat bacterial infections. However, the immune response remains elusive due to the low structural stability and poor size homogeneity of the vesicles. In this study, OMVs were used to coat self-assembled glycyrrhizic acid nanoparticles (GANs) and obtain a stable OMV vaccine. The immunoprotective effects and anti-infection efficacy were evaluated in vivo and in vitro.The OMVs were prepared by ultrafiltration method and fused with GAN through mechanical extrusion. The characteristics, including morphology, hydrodynamic size, zeta potential, and stability were evaluated. The in vitro immunological function of GAN-OMV on the macrophages and in vivo immune efficacy and anti-infection effect were examined and compared.The results showed that the GAN-OMV were homogenous with a size of 130 nm and a stable core-shell structure. Micropinocytosis-dependent and clathrin-mediated endocytotic pathways effectively internalized the GAN-OMV into the macrophages and promoted cell proliferation, cytokine secretion, and M1 polarization. Furthermore, subcutaneous GAN-OMV vaccination contributed to significantly higherIn this study, GAN-OMV was developed successfully to stimulate Th1/Th2/Th17 immune responses against Bb and provide a promising strategy for novel vaccine development against the microbial pathogen.

The objective of this study was to assess the effects of dietary supplementation with Clostridium butyricum (CB) and a bacteriophage cocktail (BP) on growth performance, serum biochemical parameters, intestinal digestive and oxidase enzymes, intestinal morphology, immune responses, and the cecum microbiota in rabbits. In total, 108 New Zealand rabbits (5 weeks old) were randomly and equally allotted into three dietary treatment groups (four replicates per treatment, n = 36/treatment): (1) the control (CN) group—rabbits fed the basal diet; (2) CB group—rabbits fed the basal diet supplemented with 100 mg/kg diet Clostridium butyricum; and (3) BP group—rabbits fed the basal diet supplemented with 200 mg/kg diet BP cocktail, respectively, for 6 weeks. Compared with the CN diet, dietary CB and BP inclusion increased the average daily gain (ADG) and average daily feed intake (ADFI) and decreased the feed/gain (F/G) ratio of rabbits. Furthermore, CB increased the digestive enzyme activity (α-amylase and trypsin in the ileum); the chymotrypsin activity was also significantly increased in the duodenum and jejunum. Supplementation with CB significantly enhanced antioxidant capacity (SOD and GSH-Px) in the jejunum and ileum and reduced MDA levels. Additionally, rabbits fed CB had significantly elevated villus height (V) and (V/C) ratios but reduced crypt depth (C). Moreover, dietary CB supplementation markedly increased the ileal expression of tight junction proteins (occludin, ZO-1, and claudin-1) and increased secretory immunoglobulin A (sIgA) production. High-throughput sequencing indicated that the microbiota in the rabbit intestine was altered by CB and BP. Venn diagrams and heatmap plots revealed that the gut microbial community composition varied obviously among rabbits fed different diets. Specifically, CB increased the relative abundance of beneficial bacteria to maintain intestinal barrier homeostasis, whereas BP decreased the relative abundance of Gammaproteobacteria, which included a plenty of pathogenic bacteria.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen that has threatened the global swine industry for almost 30 years. Because current vaccines do not provide complete protection, exploration of new preventive strategies is urgently needed. Here, we combined a heat-labile enterotoxin B subunit of Escherichia coli (LTB) and ginsenoside Rg1 to form an intranasal adjuvant and evaluated its enhancement of immune responses in mice when added to an inactivated-PRRSV vaccine. The combination adjuvant synergistically elicited higher neutralizing and non-neutralizing (immunoglobulin G and A) antibody responses in the circulatory system and respiratory tract, and enhanced T and B lymphocyte proliferation, CD4+ T-cell priming, and cytotoxic CD4+ T cell activities in mononuclear cells from spleen and lung tissues when compared to the PRRSV vaccine alone, and it resulted in balanced Th1/Th2/Th17 responses. More importantly, we observed that the combination adjuvant also up-regulated type I interferon signaling, which may contribute to improvement in adaptive immune responses. These results highlight the potential value of a combined adjuvant approach for improving the efficacy of vaccination against PRRSV. Further study is required to evaluate the efficacy of this combined adjuvant in swine.

Vaccines, in many cases, stimulate only too weak immunogenicity to prevent infection. Therefore, adjuvants are required during their preparation to boost the immune response. We herein developed a PEGylated nano-adjuvant based on Rehmannia glutinosa polysaccharide (RGP). The addition of PEG layer exhibits enhanced immune performance of the nano-RGP. Stimulation of dendritic cells (DCs) with PEGylated nano-RGP (pRL) led to increased proliferation and cytokine production (IL-6, IL-12, IL-1β and TNF-α). The pRL was internalized into DCs via a rapid and efficient method. The mice immunized with pRL exhibited enhanced antigen-specific serum IgG and Th1-(IFN-γ), Th2-(IL-4), and Th17-(IL-17, IL-6) cytokine production, contributing to a good anti-infection performance. Furthermore, the pRL could effectively deliver the antigen to the lymph nodes (LNs), activate DC in the LN and produce enhanced CD4+and CD8+ T-cells-derived memory (CD44high CD62Lhigh), and effector (CD44high CD62Llow) as well as functional phenotypes. Our results revealed that pRL can act as a promising adjuvant with targeted delivery of antigen due to its effective activation and robust adaptive immunity induction of DCs.

Sulbactam, a class A β-lactamase inhibitor, added to cefoperazone either at a fixed 8 mg/L level of sulbactam or at a level of fixed cefoperazone: sulbactam ratio (2:1) would constitute a combination form of cefoperazone/sulbactam, which has better activities against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii than cefoperazone alone. Cefoperazone/sulbactam (1:1 or 1:2) has greater in-vitro activity against most multidrug-resistant organisms (ESBL- and AmpC-producing Enterobacteriaceae and carbapenem-resistant A. baumannii except for carbapenem-resistant P. aeruginosa) than a 2:1 ratio. However, increased sulbactam concentration may induce AmpC production. Besides, sulbactam concentration might not be readily achievable in serum if the susceptibility rates were defined by the breakpoints of higher sulbactam composites, such as ≤16/16 (1:1) or 16/32 (1:2) mg/L. Carbapenemases (KPC-, OXA-type enzymes and metallo-β-lactamases) can't be inhibited by sulbactam. Some in-vitro studies showed that increasing sulbactam composites of cefoperazone/sulbactam had no effect on carbapenem-resistant P. aeruginosa, suggesting the presence of carbapenemases or AmpC overproduction that could not be overcome by increasing sulbactam levels to recover cefoperazone activity. Sulbactam alone has good intrinsic activity against carbapenem-resistant Acinetobacter strains sometimes even in the presence of carbapenemase genes, suggesting unsteady levels of carbapenemases. In conclusion, appropriate composites of cefoperazone and β-lactamase inhibitor sulbactam may expand the clinical use if the pharmacokinetic optimization could be achieved in the human serum.

Prognosis of castration-resistant prostate cancer (CRPC) carries is poor, and no effective therapeutic regimen is yet known. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway played a predominant role and may be a promising molecular target for CRPC. However, the toxicity of the dual PI3K inhibitors in clinical trials limits their clinical efficacy for CRPC. To solve this problem, we employed a highly integrated precision nanomedicine strategy to molecularly and physically target CRPC through synergistic effects, enhanced targeted drug delivery efficiency, and reduced unwanted side-effects. Gedatolisib (Ge), a potent inhibitor of PI3K/mTOR, was formulated into our disulfied-crosslinked micelle plateform (NanoGe), which exhibits excellent water solubility, small size (23.25±2 nm), excellent stability with redox stimulus-responsive disintegration, and preferential uptake at tumor sites. NanoGe improved the anti-neoplastic effect of free Ge by 53 times in PC-3M cells and 13 times in C4-2B cells though its enhanced uptake via caveolae- and clathrin-mediated endocytic pathways and the subsequent inhibition of the PI3K/mTOR pathway, resulting in Bax/Bcl-2 dependent apoptosis. In an animal xenograft model, NanoGe showed superior efficacy than free Ge, and synergized with nanoformulated cabazitaxel (NanoCa) as a nanococktail format to achieve a cure rate of 83%. Taken together, our results demonstrate the potency of NanoGe in combination with NanoCa is potent against prostate cancer.

Lentinan (LNT), a β-1,3-linked-d-glucan with β-1,6 glucose branches, is the main bioactive component extracted from Lentinus edodes. As a carbohydrate polymer, it has attracted increasingly attention because of immune enhancement effect. Pickering emulsion has been widely used in biomedicine due to its great stability, high loading capacity, and appreciable biocompatibility. The aim of this study is to construct an adjuvant delivery system (LNTPP/OVA) (Lentinan PLGA-stabilized Pickering emulsion loading OVA antigen) which can enhance the immune activity of LNT and can together deliver model protein antigen ovalbumin (OVA) into the organism. The characterization of the LNTPP/OVA was demonstrated that the size of LNTPP/OVA was around 1050.68 nm and was stable to store at least 28 days. Pickering emulsion was spherical shape like the raspberry with the high antigen load rate at around 82.53%. Moreover, the adjuvant effect of LNTPP/OVA formulation was detected. Compared with LNT/OVA formulation, our experimental results showed that LNTPP/OVA could promote the uptake of the OVA-antigen by macrophages in vitro. In vivo experiments, LNTPP/OVA facilitated the activation of dendritic cells (DCs) and induced strong humoral and cellular immune responses carrying a Th1 and Th2 immune responses. Therefore, LNTPP/OVA formulation have the latent capacity as a vaccine transmission system.

Nanotheranostics with integrated diagnostic and therapeutic functions show exciting potentials towards precision nanomedicine. However, targeted delivery of nanotheranostics is hindered by several biological barriers. Here, we report the development of a dual size/charge- transformable, Trojan-Horse nanoparticle (pPhD NP) for delivery of ultra-small, full active pharmaceutical ingredients (API) nanotheranostics with integrated dual-modal imaging and trimodal therapeutic functions. pPhD NPs exhibit ideal size and charge for drug transportation. In tumour microenvironment, pPhD NPs responsively transform to full API nanotheranostics with ultra-small size and higher surface charge, which dramatically facilitate the tumour penetration and cell internalisation. pPhD NPs enable visualisation of biodistribution by near-infrared fluorescence imaging, tumour accumulation and therapeutic effect by magnetic resonance imaging. Moreover, the synergistic photothermal-, photodynamic- and chemo-therapies achieve a 100% complete cure rate on both subcutaneous and orthotopic oral cancer models. This nanoplatform with powerful delivery efficiency and versatile theranostic functions shows enormous potentials to improve cancer treatment., Size and charge can significantly affect delivery of therapeutic agents to tumours. Here, the authors report on nanoparticles optimised for delivery to the tumour which release smaller particles and change charge in the tumour microenvironment to optimise tumour penetration and cellular uptake.

Compared to conventional carrier-assistant drug delivery systems (DDSs), drug self-delivery systems (DSDSs) have advantages of unprecedented drug loading capacity, minimized carrier-related toxicity and ease of preparation. However, the colloidal stability and blood circulation time of DSDSs still need to be improved. Here we report on the development of a novel biomimicry drug self-delivery system by the integration of a top-down cell membrane complexing technique into our self-delivery multifunctional nano-platform made from the bottom-up approach that contains 100% active pharmaceutical ingredients (API) pheophorbide A and irinotecan conjugates (named PI). Compared to conventional cell membrane-coated nanoparticles with a polymer framework as the core and a relatively low drug loading capacity, this system consisting of red blood cell membrane vesicle complexed PI (RBC-PI) is polymer-free with up to 50% API loading. RBC-PI exhibited 10 times higher area under curve in a pharmacokinetic study and a much lower macrophage uptake compared with the parent PI nanoparticles. RBC-PI retained the excellent chemophototherapeutic effects of the PI nanoparticles, but possessed superior anti-cancer efficacy with prolonged blood circulation, improved tumor delivery, and enhanced photothermal effects in animal models. This system represents a novel example of using a cell membrane complexing technique for the effective surface modification of DSDSs. This is also an innovative study to form a polymer-free cell membrane nanoparticle complexing with positive surface-charged materials. This biomimicry DSDS takes advantage of the best features from both systems to make up for each other's shortcomings and provides all the critical features for an ideal drug delivery system.

The objective of this study was to assess the effects of dietary supplementation with Clostridium butyricum (CB) and a bacteriophage cocktail (BP) on growth performance, serum biochemical parameters, intestinal digestive and oxidase enzymes, intestinal morphology, immune responses, and the cecum microbiota in rabbits. In total, 108 New Zealand rabbits (5 weeks old) were randomly and equally allotted into three dietary treatment groups (four replicates per treatment, n = 36/treatment): (1) the control (CN) group—rabbits fed the basal diet, (2) CB group—rabbits fed the basal diet supplemented with 100 mg/kg diet Clostridium butyricum, and (3) BP group—rabbits fed the basal diet supplemented with 200 mg/kg diet BP cocktail, respectively, for 6 weeks. Compared with the CN diet, dietary CB and BP inclusion increased the average daily gain (ADG) and average daily feed intake (ADFI) and decreased the feed/gain (F/G) ratio of rabbits. Furthermore, CB increased the digestive enzyme activity (α-amylase and trypsin in the ileum), the chymotrypsin activity was also significantly increased in the duodenum and jejunum. Supplementation with CB significantly enhanced antioxidant capacity (SOD and GSH-Px) in the jejunum and ileum and reduced MDA levels. Additionally, rabbits fed CB had significantly elevated villus height (V) and (V/C) ratios but reduced crypt depth (C). Moreover, dietary CB supplementation markedly increased the ileal expression of tight junction proteins (occludin, ZO-1, and claudin-1) and increased secretory immunoglobulin A (sIgA) production. High-throughput sequencing indicated that the microbiota in the rabbit intestine was altered by CB and BP. Venn diagrams and heatmap plots revealed that the gut microbial community composition varied obviously among rabbits fed different diets. Specifically, CB increased the relative abundance of beneficial bacteria to maintain intestinal barrier homeostasis, whereas BP decreased the relative abundance of Gammaproteobacteria, which included a plenty of pathogenic bacteria.

Aspergillus-associated infection might comprise up to 23–29% of severe influenza patients from the community throughout stay in an intensive care unit (ICU). In Taiwan, cases of severe influenza with aspergillosis are increasingly reported. Therefore, we describe the relative risk of mortality among severe influenza patients with aspergillosis and other coinfections compared to severe influenza patients without Aspergillus coinfections. Methods: We retrospectively reviewed 124 adult patients with severe influenza in a tertiary medical center in southern Taiwan from January 2015 through March 2016. The definition of probable aspergillosis required abnormal radiological findings and positive Aspergillus galactomannan (GM) antigen and/or Aspergillus isolation. Results: Probable aspergillosis (detected throughout the whole course) and other coinfections (only community-acquired) were diagnosed in 21 (17%) and 38 (31%) of all patients respectively. Klebsiella pneumoniae (36.8%), Pseudomonas aeruginosa (31.6%) and Staphylococcus aureus (31.6%) were the most frequent isolates of other coinfections. In-ICU mortality of Aspergillus group (66.7%) was significantly higher than other coinfections (23.7%, p = 0.001) or control group without coinfections (15.4%, p

Nanomedicine, the medical application of nanotechnology, promises a seemingly limitless range of applications from drug delivery to adjuvants and therapeutics. Our current research is focused on natural polymer-based liposome adjuvants. With the aim of inducing protective and long-lasting immunity, the immunological adjuvant activity of Rehmannia glutinosa polysaccharide liposome (RGPL) was investigated. In vivo, the splenic lymphocyte proliferation ratios and ovalbumin-specific immunoglobulin G titers of ovalbumin-RGPL-vaccinated mice were significantly upregulated. In draining lymph nodes, the expression of MHC II+CD11c+ and CD86+CD11c+ was increased by RGPL; in addition, the percentages of central memory cells (TCM) and effector memory cells (TEM) were also elevated. RGPL could effectively provide adequate antigen exposure in lymph nodes. In vitro, RGPL could promote dendritic cell maturation and enhance dendritic cell functions, such as the mixed lymphocyte reaction and antigen presentation. Overall, the results demonstrated that RGPL has the potential to act as an effective controlled release vaccine adjuvant.

Background Rabbit breeding has developed into a large-scale industry, and as such, the incidence of dermatophytosis in rabbits has become increasingly common. A rabbit model with Trichophyton mentagrophytes infection was established to study the changes within the immune responses after fungal infection. Methods After the T. mentagrophytes challenge on skin, pathogens on the skin were isolated from the rabbits in the fungal infection (FI) groups 20 days. Fungal observation under microscope were carried out. Identification of strains was achieved by polymerase chain reaction (PCR) using the CDR1 gene. The collected anticoagulant blood samples were analyzed for various blood cell parameters. The levels of antibodies, including IgM and IgA, cytokines, including IL-2, IL-6, and macrophage colony-stimulating factor (M-CSF), and soluble CD4 and CD8 in the serum of the FI group vs. the control group were determined independently. RNA isolation from blood samples and fluorescence-based quantitative PCR were carried out for the mRNA level of M-csf 20 days after fungal challenge. Results Our model resulted in typical symptoms of dermatophytosis on rabbit skin after challenged with fungus. Pathogens isolated from the infected rabbit skin were confirmed to be T. mentagrophytes by microscopic examination and PCR. The number of lymphocytes in the blood of the FI group was significantly decreased in comparison to the control group 2 days after the fungal challenge, but was significantly increased in comparison the control group 10 days after the fungal challenge (P P P P P P P P P P M-csf mRNA level of the FI group was significantly higher than the control group 20 days after fungal challenge (P Conclusions This study demonstrates how the immune system responds to infection with T. mentagrophytes and provides potential targets for the prevention and treatment of dermatophytosis.

The plasmid-mediated extended-spectrum &beta, lactamases (ESBLs) and AmpC &beta, lactamases in Enterobacter spp. have increasingly been reported. In this study, we investigated the prevalence of the plasmid-mediated &beta, lactamases in Enterobacter cloacae from bloodstream isolates at a medical center in southern Taiwan. ESBL and ampC genes were detected by PCRs and DNA sequencing. Conjugation experiments were conducted to confirm the transferability of the genetic resistance trait. Among 41 non-repetitive blood isolates of cefuroxime-resistant E. cloacae, eight isolates exhibited ESBL phenotype confirmed by double-disk synergistic tests. Nearly all the strains were susceptible to carbapenems. The prevalence rate of the plasmid-mediated blaampC genes was 73% (30/41), including one blaDHA-1, one blaMIR-6, two novel blaCMH-1 genes and other blaACT-like genes. Coexistence of plasmid-mediated blaACT and ESBL genes (10 with blaSHV-12 and one with blaCTX-M-3) was observed. Successful transmissions of the blaACT and blaCMH-1 were demonstrated in some transconjugants. The inducible or derepressed CMH-1 had expanded activity of isolates versus ceftazidime. Enterobacterial repetitive intergenic consensus (ERIC)-PCR analysis and pulsotype showed distinct patterns suggesting non-clonal relationship. In conclusion, plasmid-mediated blaACT-like ampC genes in E. cloacae isolates have been highly prevalent in southern Taiwan and may continue genetic evolution, contributing to the complexities in antibiotic-resistant mechanisms.

The plasmid-mediated extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases in Enterobacter spp. have increasingly been reported. In this study, we investigated the prevalence of the plasmid-mediated β-lactamases in Enterobacter cloacae from bloodstream isolates at a medical center in southern Taiwan. ESBL and ampC genes were detected by PCRs and DNA sequencing. Conjugation experiments were conducted to confirm the transferability of the genetic resistance trait. Among 41 non-repetitive blood isolates of cefuroxime-resistant E. cloacae, eight isolates exhibited ESBL phenotype confirmed by double-disk synergistic tests. Nearly all the strains were susceptible to carbapenems. The prevalence rate of the plasmid-mediated blaampC genes was 73% (30/41), including one blaDHA-1, one blaMIR-6, two novel blaCMH-1 genes and other blaACT-like genes. Coexistence of plasmid-mediated blaACT and ESBL genes (10 with blaSHV-12 and one with blaCTX-M-3) was observed. Successful transmissions of the blaACT and blaCMH-1 were demonstrated in some transconjugants. The inducible or derepressed CMH-1 had expanded activity of isolates versus ceftazidime. Enterobacterial repetitive intergenic consensus (ERIC)-PCR analysis and pulsotype showed distinct patterns suggesting non-clonal relationship. In conclusion, plasmid-mediated blaACT-like ampC genes in E. cloacae isolates have been highly prevalent in southern Taiwan and may continue genetic evolution, contributing to the complexities in antibiotic-resistant mechanisms.

Liposome-based vaccine delivery systems are known to enhance immune responses. Ganoderma lucidum polysaccharides (GLP) have been widely studied as immunomodulator and it could be as inducers of strong immune responses. In the research, GLP and ovalbumin (OVA) were encapsulated into liposome as vaccine and inoculated to mice. The magnitude and kinetics of the humoral and cellular immune responses were investigated. The results showed that GLP-OVA-loaded liposomes (GLPL/OVA) could induce more powerful antigen-specific immune responses than each single-component formulation. Mice immunized with GLPL/OVA displayed higher antigen-specific IgG antibodies, better splenocytes proliferation, higher cytokine secretion by splenocytes and significant activation of CD3+CD4+ and CD3+CD8+ T cells. Thus the GLPL/OVA formulation produced a heightened humoral and cellular immune response, with an overall Th1 bias. Enhanced immune responses elicited by the GLPL/OVA formulation might be attributed to effective activation and mature of DC in draining lymph nodes. Overall, these findings indicate that GLPL have the potential to enhance immune responses as vaccine delivery systems.

One acidic polysaccharide named EPS-1 was isolated from the aqueous extract of the leaves of Epimedium acuminatum Franch. It may be composed of 1,4-linked α-d-GalpA, 1,3,4-linked α-d-GalpA, 1,6-linked β-d-Galp and terminal α-l-Rhap residues in a molar ratio of 11.0:1.0:1.0:1.0 by chemical and spectroscopic analysis. EPS-1 possessed immune modulation effects on peripheral T lymphocyte and immature chBM-DCs such as promoting the proliferation and cytokine secretion of these cells and increasing the phagocytosis ability of immature chBM-DCs.

The activation of murine peritoneal macrophages by Ganoderma lucidum polysaccharides liposomes (GLPL) was investigated in vitro. After treatment with GLPL, the changes of the nitric oxide (NO) secretion and iNOS (inducible nitric oxide synthase) activity were evaluated. The results showed that NO production and iNOS activity of macrophages were enhanced compared to GLP and BL group. In addition, both the phagocytic activity and levels of cytokines IL-1β, TNF-α and IFN-γ were enhanced in the peritoneal macrophages of mice by stimulation of GLPL. The expression of the major histocompatibility complex class II molecule (MHC II) on the surface of peritoneal macrophages significantly increased. These indicated that GLPL could enhance the activation of peritoneal macrophages and their potential for use as a delivery system of GLP.

Photodynamic therapy (PDT) is a promising non-invasive therapeutic modality that has been proposed for treating prostate cancer, but the procedure is associated with limited efficacy, tumor recurrence and photo-toxicity. In the present study, we proposed to develop a novel multifunctional nano-platform for targeted delivery of heat, reactive oxygen species (ROS) and heat shock protein 90 (Hsp90) inhibitor simultaneously for combination therapy against prostate cancer. This new nano-platform combines two newly developed entities: 1) a unique organic and biocompatible nanoporphyrin-based drug delivery system that can generate efficient heat and ROS simultaneously with light activation at the tumor sites for dual-modal photothermal- and photodynamic- therapy (PTT/PDT), and 2) new nano-formulations of Hsp90 inhibitors that can decrease the levels of pro-survival and angiogenic signaling molecules induced by phototherapy, therefore, further sensitizing cancer cells to phototherapy. Furthermore, the nanoparticles have activatable near infrared (NIR) fluorescence for optical imaging to conveniently monitor the real-time drug delivery in both subcutaneous and orthotopic mouse models bearing prostate cancer xenograft. This novel multifunctional nano-platform has great potential to improve the care of prostate cancer patients through targeted combination therapy.

The widespread multidrug-resistant Enterobacteriaceae pose a serious therapeutic challenge. Colistin and tigecycline are potential antimicrobial agents for treating infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae . We evaluated the in-vitro activity of colistin sulfate against 253 ESBL producers isolated from patients admitted to a medical center in southern Taiwan ( Escherichia coli , n = 82; Klebsiella pneumoniae , n = 102; Enterobacter cloacae , n = 34; and Serratia marcescens , n = 35). Colistin showed promising in-vitro activity against E. coli, K. pneumoniae, and E. cloacae, but not S. marcescens. One ESBL-producing K. pneumoniae strain with resistance to carbapenems (ertapenem, imipenem, and meropenem) was selected for time-killing studies. A combination of colistin and tigecycline showed synergism, but there was an inoculum effect. In conclusion, colistin was active against most ESBL-producing Enterobacteriaceae , and a combination of colistin with tigecycline was synergistic against some highly resistant strains, even those with carbapenem resistance.

Bordetella bronchiseptica (B. bronchiseptica) causes a respiratory disease in rabbits. To determine the proteins of B. bronchiseptica in rabbits related to the disease, differentially accumulated proteins in B. bronchiseptica-infected cells are identified by comparative proteomic analysis. Comparative proteomic analysis detects 5814 proteins and quantifies 4854 of these. Fifty eight upregulated and 38 downregulated proteins are identified in spleen tissue after B. bronchiseptica infection of rabbits (both p < 0.05). The significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways are ribosome, biosynthesis of amino acids, biosynthesis of amino acids, protein export, and carbon metabolism etc. (all p < 0.01). Significantly enriched KEGG pathways include 'ocu03010 ribosome' (a); 'ocu00260 glycine, serine threonine metabolism'. Analyses of control and infected spleen cells detect responses to B. bronchiseptica infection. Many differentially affected proteins are evident, and reflect different biological changes and diverse subcellular localizations between control and infected spleen cells. Infection markedly alters the expressions of proteins linked to the serine protease system, with the 'phagosome,' 'biosynthesis of amino acids,' 'glycine, serine threonine metabolism,' 'intestinal immune network for IgA production', and 'amino sugar and nucleotide sugar metabolism' associated with B. bronchiseptica infection. The result will inform studies of responses to B. bronchiseptica infections in rabbits.

Monitoring of in vivo drug release from nan by non-invasive approaches Remains very challenging. Herein we report on novel redox-responsive polymeric magnetosomes (PolyMags) with tunable magnetic resonance imaging (MRI) properties for in vivo drug release monitoring and effective dual-modal cancer therapy. The encapsulation of doxorubicin (DOX) significantly decreased PolyMags’ T(2) contrast enhancement and transverse relaxation rate R(2), depending on the drug loading level. The T(2) enhancement and R(2) could be recovered once the drug was released upon PolyMags’ disassembly. T(2) & T(2)* MRI and diffusion-weighted imaging (DWI) were utilized to quantitatively study the correlation between MRI signal changes and drug release, and discover the MR tuning mechanisms. We visualized the in vivo drug release pattern based on such tunable MRI capability via monitoring the changes in T(2)-weighted images, T(2) & T(2)* maps and R(2) & R(2)* values. Interestingly, the PolyMags possessed excellent photothermal effect, which could be further enhanced upon DOX loading. The PolyMags were highly efficacious to treat breast tumors on xenograft model with tumor-targeted photothermal-and chemo-therapy, achieving a complete cure rate of 66.7%. The concept reported here is generally applicable to other micellar and liposomal systems for image-guided drug delivery & release applications toward precision cancer therapy.

This study demonstrated that the use of a ITO/AgNW/ITO stacked structure could considerably enhance the mechanical flexibility of a transparent conducting oxide while minimizing AgNWs caused rough surface morphology. The bending test showed the electrical resistance variation of the stacked film could reach 1% much lower than that of the initial ITO of 32%. The top ITO also improve the adhesion of AgNWs on ITO. Optimization on the thickness of AgNWs and top ITO layer is necessary for better optical and surface morphological characteristics.

Photodynamic therapy is a promising and effective non-invasive therapeutic approach for the treatment of bladder cancers. Therapies targeting HSP90 have the advantage of tumor cell selectivity and have shown great preclinical efficacy. In this study, we evaluated a novel multifunctional nanoporphyrin platform loaded with an HSP90 inhibitor 17AAG (NP-AAG) for use as a multi-modality therapy against bladder cancer. NP-AAG was efficiently accumulated and retained at bladder cancer patient-derived xenograft (PDX) over 7 days. PDX tumors could be synergistically eradicated with a single intravenous injection of NP-AAG followed by multiple light treatments within 7 days. NP-AAG mediated treatment could not only specifically deliver 17AAG and produce heat and reactive oxygen species, but also more effectively inhibit essential bladder cancer essential signaling molecules like Akt, Src, and Erk, as well as HIF-1α induced by photo-therapy. This multifunctional nanoplatform has high clinical relevance and could dramatically improve management for bladder cancers with minimal toxicity.

Conventional drug delivery systems contain substantial amounts of excipients such as polymers and lipids, typically with low drug loading capacity and lack of intrinsic traceability and multifunctionality . Here, we report fully active pharmaceutical ingredient nanoparticles (FAPIN) which were self-assembled by minimal materials, but seamlessly orchestrated versatile theranostic functionalities including: i) self-delivery: no additional carriers were required, all components in the formulation are active pharmaceutical ingredients; ii) self-indicating: no additional imaging tags were needed. The nanoparticle itself was composed of 100% imaging agents , so that the stability, drug release, subcellular dispositions, biodistribution and therapeutic efficacy of FAPINs can be readily visualized by ample imaging capacities, including energy transfer relay dominated, dual-color fluorogenic property, near-infrared fluorescence imaging and magnetic resonance imaging; and iii) highly effective trimodality cancer therapy, encompassing photodynamic-, photothermal- and chemo-therapies . FAPINs were fabricated with very simple material (a photosensitizer-drug conjugate), unusually achieved ∼10 times better in vitro antitumor activity than their free counterparts, and were remarkably efficacious in patient-derived xenograft (PDX) glioblastoma multiforme animal models. Only two doses of FAPINs enabled complete ablation of highly-malignant PDX tumors in 50% of the mice.