Zingerone enhances the antitumor activity of attenuated Salmonella-mediated cancer immunotherapy by promoting tumor infiltration by host immune cells

Bacteria-mediated cancer immunotherapy (BCI) suppresses tumor progression in two ways: the bacteria themselves kill tumor cells, and they elicit robust host immune responses. However, this does not eradicate tumors completely or prevent metastasis. Therefore, the immune responses elicited by BCI must be backed up by other therapies such as chemotherapy. Zingerone has anticancer activity and modulates T cell-mediated immune responses. Here, we examined the antitumor effects of zingerone/BCI combination therapy. We show that that zingerone 1) enhances St.ΔppGpp-mediated antitumor effects, but reduces survival of tumor-colonizing bacteria by promoting recruitment of tumor-infiltrating neutrophils; 2) amplifies St.ΔppGpp-mediated immune responses by stimulating tumor infiltration by macrophages, natural killer cells, and CD4+ and CD8+ T cells; and 3) enhances St.ΔppGpp-mediated macrophage phagocytosis, leading to tumor eradication. These findings suggest that the zingerone/St.ΔppGpp combination has synergistic antitumor effects, making it a promising approach to cancer immunotherapy

Tie strength, absorptive capacity and innovation performance in Chinese manufacturing industries

Purpose In innovation networks, firm innovation performance is affected by external tie strength and internal knowledge absorptive capacity. This study aims to empirically examine the path relationship between tie strength, absorptive capacity and firm innovation performance in Chinese manufacturing industries, thus enhance our understanding on the mechanism between innovation network and innovation performance. Design/methodology/approach The authors have conducted a survey among Chinese manufacturers in four industries (textile and garment, household appliance, IT and electronics and motor vehicle assemblers) that are located in North, East, Central and South China, respectively, with a valid response from 278 manufacturers. Structural equation model is used to analyze the results. Findings This study demonstrates that in Chinese Manufacturing industry, tie strength is positively related to innovation performance. The authors also find that absorptive capacity has a positive impact on innovation performance and it mediates the relationship between tie strength and innovation performance. Then, the authors analyze the effect of ownership, industry and sub-region, and the results show that in private firms and traditional manufacturers, and the firms located in North and Eastern China, tie strength has no direct effect on innovation outcomes, but it can influence innovation indirectly through absorptive capacity. Originality/value This study further supports that in Chinese guanxi culture, strong ties with other innovation partners can improve the firm’s absorptive capacity and thus improve innovation performance. The results also suggest that a firm’s absorptive capacity has a significant mediating effect on the relationship between tie strength and innovation performance

Synthesis and thermoresponsive property of end-functionalized poly(N-isopropylacrylamide) with pyrenyl group

N-Isopropylacrylamide (NIPAM) was polymerized using 1-pyrenyl 2-chloropropionate (PyCP) as the initiator and CuCl/tris[2-(dimethylamino)ethyl]amine (Me6TREN) as the catalyst system. The polymerizations were performed using the feed ratio of [NIPAM]0/[PyCP]0/[CuCl]0/[Me6TREN]0 = 50/1/1/1 in DMF/water of 13/2 at 20 ｰC to afford an end-functionalized poly(N-isopropylacrylamide) with the pyrenyl group (Py-PNIPAM). The characterization of the Py-PNIPAM using matrix-assisted laser desorption ionization time-of-flight mass spectrometry provided the number-average molecular weight (Mn,MS). The lower critical solution temperature (LCST) for the liquid-solid phase transition was 21.7, 24.8, 26.5, and 29.3 ｰC for the Py-PNIPAMs with the Mn,MS's of 3000, 3400, 4200, and 5000, respectively; hence, the LCST was dramatically lowered with the decreasing Mn,MS. The aqueous Py-PNIPAM solution below the LCST was characterized using a static laser light scattering (SLS) measurement to determine its molar mass, Mw,SLS. The aqueous solutions of the Py-PNIPAMs with the Mn,MS's of 3000, 3400, 4200, and 5000 showed the Mw,SLS of 586,000, 386,000, 223,000, and 170,000, respectively. Thus, lowering the LCST for Py-PNIPAM should be attributable to the formation of the PNIPAM aggregates. The LCST of 21.7 ｰC for Py-PNIPAM with the Mn,MS of 3000 was effectively raised by adding β-cyclodextrin (β-CD) and reached the constant value of 26 ｰC above the molar ratio of [β-CD]/[Py-PNIPAM] = 2/1, suggesting that β-CD formed an inclusion complex with pyrene in the chain-end to disturb the formation of PNIPAM aggregates, thus raising the LCST

Synthesis and Photocrosslinking Reaction of N-Allylcarbamoylmethyl Cellulose Leading to Hydrogel

The reaction of the carboxymethyl cellulose sodium salt (Na-CMC) (degrees of substitution (DS) = 1.2) with N-hydroxysuccinimide (Su-OH) in the presence of 1-hydroxybenzotriazole and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) was carried out in water to obtain the Su-OH ester of carboxymethyl cellulose, Su-CMC, with the DS values of 0.19 – 1.04. N-Allylcarbamoylmethyl cellulose (Allyl-CMC), which was prepared from the reaction of Su-CMC with an excess amount of allylamine, was crosslinked by UV-irradiation. In addition, the photocrosslinked Allyl-CMC film was swollen with water to form a hydrogel having a relatively high water-swelling property, e.g., the degree of swelling (ds) was ca. 360% for Allyl-CMC with the DS of 0.93

Enhancing mechanical strength, tribological properties, cytocompatibility, osteogenic differentiation, and antibacterial capacity of biodegradable Zn-5RE (RE = Nd, Y, and Ho) alloys for potential bone-implant application

Degradable zinc (Zn) based metals exhibit great promise as potential load-bearing bone-implant materials due to their suitable biodegradability, good fabricate-friendliness, biocompatibility, and favorable osteogenesis-promoting capacity. Nevertheless, most as-cast Zn-based metals display poor mechanical properties due to their coarse grain size and few slip systems, which is challenging to meet bone-implant application requirements. Herein, the alloying using rare earth (RE) elements of neodymium (Nd), yttrium (Y), and holmium (Ho) combined with hot-rolling was used to prepare the hot-rolled (HR) Zn-5RE binary alloys for load-bearing bone fixation or bone repair applications. HR Zn–5Y sample demonstrated the best mechanical properties matching with an ultimate tensile strength of ∼260 MPa, yield strength of ∼200 MPa, elongation of ∼43.5%, strength-elongation product of ∼11.3 GPa%, and macro-hardness of ∼104.7 HB among the HR samples, close to the requirements of mechanical properties for degradable bone-implant materials. HR Zn–5Y sample exhibited the lowest corrosion rate of ∼178 μm/y measured by electrochemical polarization testing, the degradation rate of ∼29 μm/y measured by static immersion testing, and high tribological properties in Hanks’ solution. The diluted Zn–5Y extract showed an appropriate cytocompatibility to 3T3 and MG-63 cells and moderate osteogenic differentiation ability to 3T3 cells among HR Zn-5RE and pure Zn extracts. Meanwhile, the HR Zn–5Y sample showed a suitable and effective antibacterial capacity against S. aureus and E. coli. Overall, the HR Zn–5Y sample is a promising moderate load-bearing bone-implant material for bone pins, plates, and guiding bone regeneration membrane application

Precise Synthesis and Thermoresponsive Property of Poly(ethyl glycidyl ether) and Its Block and Statistic Copolymers with Poly(glycidol)

In this paper, we describe a comprehensive study of the thermoresponsive properties of statistic copolymers and multiblock copolymers synthesized by poly(glycidol)s (PG) and poly(ethyl glycidyl ether) (PEGE) with different copolymerization methods. These copolymers were first synthesized by ring-opening polymerization (ROP), which was initiated by tert-butylbenzyl alcohol (tBBA) and 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)phosphoranylidenamino]-2 lambda(5),4 lambda(5)-catenadi(phosphazene) (t-Bu-P-4) as the catalyst, and then the inherent protective groups were removed to obtain the copolymers without any specific chain end groups. The thermoresponsive property of the statistic copolymer PG(x)-stat-PEGE(y) was compared with the diblock copolymer PG(x)-b-PEGE(y), and the triblock copolymers were compared with the pentablock copolymers. Among them, PG-stat-PEGE, PG-b-PEGE-b-PG-b-PEGE-b-PG, and PEGE-b-PG-b-PEGE-b-PG-b-PEGE, and even the specific ratio of PEGE-b-PG-b-PEGE, exhibited LCST-type phase transitions in water, which were characterized by cloud point (T-cp). Although the ratio of x to y affected the value of the T-cp of PG(x)-stat-PEGE(y), we found that the disorder of the copolymer has a decisive effect on the phase-transition behavior. The phase-transition behaviors of PG-b-PEGE, part of PEGE-b-PG-b-PEGE, and PG-b-PEGE-b-PG copolymers in water present a two-stage phase transition, that is, firstly LCST-type and then the upper critical solution temperature (UCST)-like phase transition. In addition, we have extended the research on the thermoresponsive properties of EGE homopolymers without specific alpha-chain ends

Synthesis and conformation effects of poly(phenylacetylene)s having chiral and racemic polylactide pendants

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