Abstract Co-delivery of nucleic acids and chemotherapeutics has a potential to efficaciously treat human diseases via their synergetic effects. Activable therapeutic tools at the nanoscale are ...suitable platforms for combination therapy. In this study, we have developed a multifunctional nanoscaled delivery system simultaneously integrated with passive and active tumor targeting, cell membrane translocation, pH-triggered drug release and co-delivery strategies. Poly (ethyleneimine) (PEI)-polyethylene glycol (PEG) copolymer was synthesized with coupling TAT to the distal end of PEG for membrane activity. The functional amino group of PEI was used to chemically conjugate doxorubicin (DOX) via a pH-sensitive hydrazone linkage. Meanwhile, the cationic PEI backbone could complex DNA to DOX loaded-TAT modified polyion complex micelles (NPIC). To achieve double targeting effect to tumor vascular endothelial cells and tumor cells either by active or passive targeting, a virus mimetic shell functioned with NGR was conferred by electrostatic adsorption of sulfamerazine (SA)-PEG-NGR on the surface of NPIC to obtain DOX loaded targeted PIC micelles (TPIC). The multifunctional nanoscaled delivery system was established to comprehensively improve the efficacy of cancer therapy through the synergistic effect of gene therapy with chemotherapy. Consequently, the system was shown to be a promising carrier for the co-delivery of DNA and DOX, leading to the efficiency of gene transfection and anti-tumor activity in vitro.
Dendritic cells (DCs) and macrophages play important roles in maintaining intestinal homeostasis. However, the molecular mechanisms that regulate the differentiation and responses of intestinal DCs ...and macrophages remain poorly understood. Here, we have identified microRNA miR-223 as a key molecule for regulating these processes. Deficiency of miR-223 led to a significantly decreased number of intestinal CX3CR1hi macrophages at steady state. Both intestinal CX3CR1hi macrophages and CD103+ conventional DCs (cDCs) in miR-223-deficient mice exhibited a strong pro-inflammatory phenotype. Moreover, miR-223-deficient monocytes gave rise to more monocyte-derived DCs (moDCs) and produced more pro-inflammatory cytokines upon stimulation. Using a mouse model of colitis, we demonstrated that the miR-223 deficiency resulted in more severe colitis. Target gene analysis further identified that the effects of miR-223 on DCs and macrophages were mediated by directly targeting C/EBPβ. Taken together, our study identifies a role for miR-223 as a critical regulator of intestinal homeostasis.
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•The number of CX3CR1hi intestinal macrophages decreased in miR-223-deficient mice•The intestinal APC in miR-223-deficient mice showed a more pro-inflammatory phenotype•miR-223 exerted its effects on APCs by targeting C/EBPβ
Zhou et al. identify an important role for miR-223 in the maintenance of intestinal homeostasis. They show that, in the absence of miR-223, intestinal dendritic cells and macrophages display a pro-inflammatory phenotype and that miR-223 exerts its effects through targeting C/EBPβ.
In a traditional antenna array direction finding system, all the antenna sensors need to work or shut down at the same time, which often leads to signal crosstalk, signal distortion, and other ...electromagnetic compatibility problems. In addition, the direction-finding algorithm in a traditional system needs a tremendous spectral search, which consumes considerable time. To compensate for these deficiencies, a reconfigurable antenna array direction finding system is established in this paper. This system can dynamically load part or all of the antennas through microwave switches (such as a PIN diode) and conduct a fast direction of arrival (DOA) search. First, the hardware structure of the reconfigurable antenna is constructed. Then, based on the conventional spatial domain search algorithm, an improved transform domain (TD) search algorithm is proposed. The effectiveness of the system has been proven by real experiments, and the advantage of the system has been verified by detailed simulations.
Purpose
Hartmann’s procedure is traditionally performed in emergency situations where single-step procedures with immediate anastomosis may be unsafe. However, it can be associated with significant ...morbidity and low colostomy reversal rate. Whilst randomised controlled trials and a Cochrane review have reported strong evidence of laparoscopic over open colectomies, no such reviews have been performed for Hartmann’s procedure. Hence, this paper aims to summarise the existing evidence to determine the efficacy of laparoscopic Hartmann’s procedure over its open counterpart.
Methods
Embase, Medline and Cochrane databases were searched from inception to 15 November 2020 for keywords relating to ‘laparoscopy’ and ‘Hartmann’ using strict inclusion and exclusion criteria. Odds ratio was estimated for dichotomous outcomes and weighted mean difference was estimated for continuous outcomes.
Results
From the 836 articles yielded from the search strategy, 12 articles were selected for meta-analysis. Pooled analysis revealed that laparoscopic Hartmann’s procedure (LHP) allows for a shorter length of stay, and a lower risk of overall surgical site infections and superficial surgical site infections. There was no significant difference in other outcomes. Single-arm analysis of LHP also showed an unprecedented high colostomy reversal rate of over 80%.
Conclusion
In clinically suitable patients, laparoscopic Hartmann’s procedure has benefits over open Hartmann’s procedure. Despite the selection bias of single-arm studies, LHP has reported a high stoma reversal rate of over 80%. Future well-controlled studies should be done to affirm the findings.
Purpose Cationic solid lipid nanoparticles (SLN) have established themselves during the past decades. They can efficiently bind DNA directly via ionic interaction and mediate gene transfection. One ...major problem with SLN is the lack of cell-targeting ability. In the present study, a mannan-based PE-grafted ligand was synthesized and used for the surface modification of DNA-loaded cationic SLN to prepare Man-SLN-DNA. Methods For in vitro test, the cytotoxicity and transfection investigation was carried out on murine macrophage cell line RAW 264.7. For in vivo evaluation, Man-SLN-DNA was delivered into the lung of the rats, and the alveolar macrophages (AM) were isolated for the fluorescence determination of transfection efficiency. Results When compared with non-modified SLN-DNA and Lipofectamine 2000-DNA, Man-SLN-DNA produced the highest gene expressions, especially in vivo. Conclusion These results demonstrated the active targeting ability of this kind of mannan-modified DNA-loaded vehicles, which may have great potential for targeted gene delivery.
The purpose of the study was to design lipid-based-nanosuspensions (LNS) for Docetaxel (DTX) without Tween 80 for clinical intravenous administration (i.v.). DTX-LNS were prepared by high pressure ...homogenization method, and then lyophilization was carried out to improve the stability. The physical–chemical properties in terms of particle size, size distribution, zeta potential and morphology were evaluated, respectively. The
in vitro cytotoxic activity was assessed by MTT against SKOV-3 and malignant melanoma B16 cells. The
in vivo pharmacokinetics, tissue distribution as well as antitumor efficacy were investigated in B16 melanoma-bearing Kunming mice. The particle size and zeta potential of DTX-LNS were (200.0
±
3.42)
nm and (−11.15
±
0.99)
mV, respectively. Compared with Duopafei
®, it was shown that DTX-LNS exhibited higher antitumor efficacy by reducing tumor volume (
P
<
0.05) and increasing survival rate in B16 melanoma-bearing mice and strongly reduced the anticancer drug toxicity. The results of biodistribution studies clearly indicated the superiority of DTX-LNS to Duopafei
® in increasing the accumulation of DTX within tumor and the organs rich in macrophages (liver, lungs and spleen), while, the drug concentration in heart and kidney decreased. Together these results suggested that DTX-LNS could effectively inhibit tumor growth, reduce toxicity during the therapeutic procedure and hold the potential to be an appropriate choice for the clinical administration of DTX.
Plasmacytoid dendritic cells (pDCs) are the major producers of type I and type III interferons (IFNs) that play essential roles in host antiviral immunity. MicroRNAs (miRs) are small, noncoding RNAs ...that can modulate many immune processes. Although molecular regulation of type I IFN production by pDCs has been studied extensively, the regulation of type III IFN production has not been studied thoroughly, particularly at posttranscriptional level. We show here that miR-21 is an essential positive regulator for the production of both IFN-α and IFN-λ by pDCs and for promoting host defense against viral infection. miR-21 was markedly upregulated in toll-like receptor (TLR)-activated pDCs and was crucial for TLR7/9 ligand- or herpesvirus-induced production of IFN-α and IFN-λ by pDCs. miR-21-deficient pDCs produced significantly lower levels of IFN-α and IFN-λ on activation than those by wild-type pDCs. Impaired antiviral immune responses were also observed in miR-21-deficient mice. Mechanistically, we identified phosphatase and tensin homolog (PTEN) as the major target of miR-21 in pDCs, and miR-21 deficiency resulted in increased expression of PTEN that suppressed TLR-mediated activation of PI3K-Akt-mTOR signaling in pDCs. Hence, our findings provide evidence that miR-21 positively regulates both IFN-α and IFN-λ production and identify an important role for miR-21 in regulating the function of pDCs and in host antiviral immunity.
Compared with uniform arrays, a generalized sparse array (GSA) can obtain larger array aperture because of its larger element spacing, which improves the accuracy of DOA estimation. At present, most ...DOA estimation algorithms are only suitable for the uniform arrays, while a few DOA estimate algorithms that can be applied to the GSA are unsatisfactory in terms of computational speed and accuracy. To compensate this deficiency, an improved DOA estimation algorithm which can be applied to the GSA is proposed in this paper. First, the received signal model of the GSA is established. Then, a fast DOA estimation method is derived by combining the weighted noise subspace algorithm (WNSF) with the concept of “transform domain” (TD). Theoretical analysis and simulation results show that compared with the traditional multiple signal classification (MUSIC) algorithm and the traditional WNSF algorithm, the proposed algorithm has higher accuracy and lower computational complexity.
Apigenin and luteolin were studied for the affinities for human serum albumin (HSA) in the presence and absence of three CdTe QDs with different sizes. The fluorescence intensities of HSA decreased ...remarkably with increasing concentration of QDs. Apigenin and luteolin resulted in obvious blue-shifts of the
λ
em of HSA from 340
nm to 330
nm and 320
nm. However, the extents of blue-shifts induced by apigenin or luteolin in the presence of QDs were much smaller than that in the absence of QDs. The quenching process of apigenin for HSA was easily affected by the QDs size than that of luteolin. QDs decreased the quenching constant from 37.23% to 52.38% for apigenin. However, QDs decreased the quenching constant from 56.18% to 60.38% for luteolin. QDs decreased the affinity of apigenin or luteolin for HSA. G-QDs, Y-QDs, and R-QDs decreased the affinity of apigenin for HSA about 14.71%, 12.65% and 6.91%. The binding affinity of apigenin for HSA increased with increasing QDs size. However, the binding affinity of luteolin for HSA decreased with increasing QDs size. G-QDs, Y-QDs, and R-QDs decreased the affinities of luteolin for HSA about 19.48%, 22.47% and 28.18%.
Metallic 1T-phase MoS2 is a newly emerging and attractive catalyst since it has more available active sites and high carrier mobility in comparison with its widely used counterpart of semiconducting ...2H-MoS2. Herein, 1T/2H-MoS2(N) (N: MoO3 nanowires were used to prepare 1T/2H-MoS2) was synthesized by using molybdenum trioxide (MoO3) nanowires as the starting material and applied in the photodegradation of antibiotic residue in water. Enhanced photocatalytic performance was observed on the obtained 1T/2H-MoS2(N), which was 2.8 and 1.3 times higher than those on 1T/2H-MoS2(P) (P: commercial MoO3 powder was used to prepare 1T/2H-MoS2) and 2H-MoS2, respectively. The active component responsible for the photodegradation was detected and a reaction mechanism is proposed.
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