Characterization of the H2/NOx reaction process over the La0.9Ce0.1Co0.9Pd0.1O3-BaO/Al2O3 catalyst.

An excellent textual properties and performance La0.9Ce0.1Co0.9Pd0.1O3-BaO/Al2O3 catalyst was synthesized. The reaction mechanism of H2/NOx over the La0.9Ce0.1Co0.9Pd0.1O3-BaO/Al2O3 catalyst was investigated by temperature programmed reduction/ desorption/ surface reaction (TPR/D/SR) technologies and in-situ diffuse reflectance Fourier transform (DRIFT) technology. The results show that cerium or palladium species are inserted into the cells of LaCoO3, as well as they synergetic promote the redox properties of the La0.9Ce0.1Co0.9Pd0.1O3-BaO/Al2O3 catalyst. Surface activated nitrates exist over the La0.9Ce0.1Co0.9Pd0.1O3-BaO/Al2O3 catalyst, with thermal stable increasing in the order: absorbed N2O4 < monodentate nitrates < chelating bidentate nitrates < nitrates unidentate < free ionic nitrates < bulk free ionic nitrates. H2 preferentially reacted with absorbed N2O4 and monodentate nitrates at low temperatures, due to their high activity. The concentration of generated NH3 from the redox reaction of H2/NOx achieves the maximum value between 350 and 450 °C over the La0.9Ce0.1Co0.9Pd0.1O3-BaO/Al2O3 catalyst. Compared with the NOx adsorption process at 50 °C, monodentate nitrates and absorbed N2O4 disappeared due to their low thermal stability, chelating bidentate nitrates become stronger, as well as free ionic nitrates converted to bulk free ionic nitrates with higher thermal stability at 350 °C. When H2 is exposed to NOx species adsorbed on La0.9Ce0.1Co0.9Pd0.1O3-BaO/Al2O3, chelating bidentate nitrates and bulk free ionic nitrates are consumed gradually, indicating that although the bulk free ionic nitrates own high stability, it also could be consumed by involving in the H2/NOx reaction at 350 °C. The quantitative H2/NO reaction experiments confirmed the results of H2-TPSR and NSR. It is beneficial to the formation of NH3 when the H2/NO ratio is more than 2.5. Comparing traditional Pt-BaO/Al2O3 catalyst, the La0.9Ce0.1Co0.9Pd0.1O3-BaO/Al2O3 catalyst exhibit an excellent performance, including considerable NH3 production property, lower N2O selectivity, and the precious metal saving.

Clinical application of indocyanine green fluorescence navigation technique in laparoscopic common bile duct exploration for complex hepatolithiasis.

BACKGROUND: This study investigated the clinical application of the indocyanine green (ICG) fluorescence navigation technique in bile duct identification during laparoscopic common bile duct exploration (LCBDE) for complex hepatolithiasis. METHODS: Eighty patients with complex hepatolithiasis were admitted to our department between January 2022 and June 2023 and randomly divided into control and observation groups. The control group underwent conventional LCBDE, while the observation group underwent LCBDE guided by ICG fluorescence. RESULTS: Intraoperatively, the observation group had shorter operation and search times for the common bile duct (CBD), as well as reduced intraoperative blood loss and fewer complications, such as conversion to laparotomy and various injuries (gastroduodenal, colon, pancreatic, and vascular) than the control group, with statistical significance (P < 0.05). Postoperatively, the observation group had lower rates of postoperative bile leakage, abdominal infection, postoperative hemorrhage, and residual stone than the control group. Additionally, the observation group demonstrated significantly shorter times for resuming flatus, removal of the abdominal drainage tube, and hospitalization than the control group, with statistical significance (P < 0.05). CONCLUSION: ICG fluorescence navigation technology effectively visualizes the bile duct, improves its identification rate, shortens the operation time, prevents biliary tract injury, and reduces the occurrence of complications.

Exploring Video Denoising in Thermal Infrared Imaging: Physics-inspired Noise Generator, Dataset and Model.

We endeavor on a rarely explored task named thermal infrared video denoising. Perception in the thermal infrared significantly enhances the capabilities of machine vision. Nonetheless, noise in imaging systems is one of the factors that hampers the large-scale application of equipment. Existing thermal infrared denoising methods, primarily focusing on the image level, inadequately utilize time-domain information and insufficiently conduct investigation of system-level mixed noise, presenting the inferior ability in the video-recorded era; while video denoising methods, commonly applied to RGB cameras, exhibit uncertain effectiveness owing to substantial dissimilarities in the noise models and modalities between RGB and thermal infrared images. In sight of this, we initially revisit the imaging mechanism, while concurrently introducing a physics-inspired noise generator based on the sources and characteristics of system noise. Subsequently, a thermal infrared video denoising dataset consisting of 518 real-world videos is constructed. Lastly, we propose a denoising model called multi-domain infrared video denoising network, capable of concentrating features from the time, space, and frequency domains to restore high-fidelity videos. Extensive experiments demonstrate that the proposed method achieves state-of-the-art denoising quality and can be successfully applied to commercial cameras and downstream vision tasks, providing a new avenue for clear videography in the thermal infrared world. The dataset and code will be available.

Fiber Flexibility Reconciles Matrix Recruitment and the Fiber Modulus to Promote Cell Mechanosensing.

The mechanical interaction between cells and the extracellular matrix is pervasive in biological systems. On fibrous substrates, cells possess the ability to recruit neighboring fibers, thereby augmenting their own adhesion and facilitating the generation of mechanical cues. However, the matrices with high moduli impede fiber recruitment, restricting the cell mechanoresponse. Herein, by harnessing the inherent swelling properties of gelatin, the flexible gelatin methacryloyl network empowers cells to recruit fibers spanning a broad spectrum of physiological moduli during adhesion. The high flexibility concurrently facilitates the optimization of fiber distribution, deformability, and modulus, contributing to the promotion of cell mechanosensing. Consequently, the randomly distributed flexible fibers with high moduli maximize the cell adhesive forces. This study uncovers the impact of fiber recruitment on cell mechanosensing and introduces fiber flexibility as a previously unexplored property, offering an innovative perspective for the design and development of novel biomaterials.

Aligned Nanofibers Promote Myoblast Polarization and Myogenesis through Activating Rac-Related Signaling Pathways.

The extracellular matrix (ECM) plays a crucial role in regulating cellular behaviors and functions. However, the impact of ECM topography on muscle cell adhesion and differentiation remains poorly understood from a mechanosensing perspective. In this study, we fabricated aligned and random electrospun polycaprolactone (PCL) nanofibers to mimic the structural characteristics of ECM. Mechanism investigations revealed that the orientation of nanofibers promoted C2C12 polarization and myogenesis through Rac-related signaling pathways. Conversely, cells cultured on random fibers exhibited spreading behavior mediated by RhoA/ROCK pathways, resulting in enhanced stress fiber formation but reduced capacity for myogenic differentiation. Our findings highlight the critical role of an ECM structure in muscle regeneration and damage repair, providing novel insights into mechanosensing mechanisms underlying muscle injury diseases.

Adipose-derived mesenchymal stem cells (MSCs) are a superior cell source for bone tissue engineering.

Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors, osteoinductive biofactors and biocompatible scaffold materials. Mesenchymal stem cells (MSCs) represent the most promising seed cells for bone tissue engineering. As multipotent stem cells that can self-renew and differentiate into multiple lineages including bone and fat, MSCs can be isolated from numerous tissues and exhibit varied differentiation potential. To identify an optimal progenitor cell source for bone tissue engineering, we analyzed the proliferative activity and osteogenic potential of four commonly-used mouse MSC sources, including immortalized mouse embryonic fibroblasts (iMEF), immortalized mouse bone marrow stromal stem cells (imBMSC), immortalized mouse calvarial mesenchymal progenitors (iCAL), and immortalized mouse adipose-derived mesenchymal stem cells (iMAD). We found that iMAD exhibited highest osteogenic and adipogenic capabilities upon BMP9 stimulation in vitro, whereas iMAD and iCAL exhibited highest osteogenic capability in BMP9-induced ectopic osteogenesis and critical-sized calvarial defect repair. Transcriptomic analysis revealed that, while each MSC line regulated a distinct set of target genes upon BMP9 stimulation, all MSC lines underwent osteogenic differentiation by regulating osteogenesis-related signaling including Wnt, TGF-ß, PI3K/AKT, MAPK, Hippo and JAK-STAT pathways. Collectively, our results demonstrate that adipose-derived MSCs represent optimal progenitor sources for cell-based bone tissue engineering.

Assembly and Utility of a Drawstring-Mimetic Supramolecular Complex.

Inspired by the drawstring structure in daily life, here we report the development of a drawstring-mimetic supramolecular complex at the molecular scale. This complex consists of a rigid figure-of-eight macrocyclic host molecule and a flexible linear guest molecule which could interact through three-point non-covalent binding to form a highly selective and efficient host-guest assembly. The complex not only resembles the drawstring structure, but also mimics the properties of a drawstring with regard to deformations under external forces. The supramolecular drawstring can be utilized as an interlocked crosslinker for poly(methyl acrylate), and the corresponding polymer samples exhibit comprehensive enhancement of macroscopic mechanical performance including stiffness, strength, and toughness.

Promoting Stem Cell Mechanosensing and Osteogenesis by Hybrid Soft Fibers.

Bone regenerative biomaterials are essential in treating bone defects as they serve as extracellular matrix (ECM) mimics, creating a favorable environment for cell attachment, proliferation, and differentiation. However, the currently used bone regenerative biomaterials mostly exhibit high stiffness, which may lead to difficulties in degradation and thus increase the risk of foreign body ingestion. In this study, we prepared soft fibrous scaffolds modified with Zn-MOF-74 nanoparticles via electrostatic spinning. The soft fibers (only 1 kPa) permit remodeling under cellular adhesive force, optimizing the mechanical cues in the microenvironment to support cell adhesion and mechanosensing. In addition, the incorporation of Zn-MOF-74 nanoparticles enables the stable and sustained release of zinc ions, promoting stem cell mechanotransduction and osteogenic differentiation. Therefore, the hybrid soft fibers facilitate the regeneration of new bone in the rat femoral defect model, which provides a promising approach for regenerative medicine.

BMP4 upregulates glycogen synthesis through the SMAD/SLC2A1 (GLUT1) signaling axis in hepatocellular carcinoma (HCC) cells.

BACKGROUND: Excessive hepatic glycogen accumulation benefits tumorigenesis and cancer cell survival. We previously reported that BMP4 has the strongest ability to promote glycogenesis among the 14 BMPs in hepatocytes and augmented hepatocellular carcinoma (HCC) cell survival under hypoxia and hypoglycemia conditions by promoting the glycolysis pathway. However, the mechanism underlying BMP4's effect on glycogenesis in HCC remains elusive. METHODS: The expression of BMP4 and SLC2A1 were acquired by analyzing the TCGA-LIHC dataset, as well as by immunohistochemical analysis of the 40 pairs of human HCC samples and para-tumor tissues. Gene expressions were detected by qPCR, immunoflurorescence staining, and Western blotting. Overexpression and silencing of BMP4 were accomplished through adenoviruses Ad-B4 and Ad-siB4 infection. Hepatic glycogen was detected by PAS staining. SLC2A1 (GLUT1) function was blocked by the inhibitor BAY-876. ChIP assay was used to determine the binding of SMADs to the promoter region of SLC2A1 in HCC cells. Lastly, the in vivo effect of BMP4-regulated SLC2A1 on HCC tumor growth was assessed in a xenograft model of HCC. RESULTS: The elevated expression of BMP4 in HCC tumor tissues was highly correlated with hepatic glycogen accumulation in clinical samples. SLC2A1 was highly expressed in HCC tumor tissue and correlated with clinical stage and prognosis. Exogenous BMP4 augmented glycogen accumulation and upregulated the expression of glycogen synthesis-related genes in Huh7 and HepG2 cells, both of which were effectively blunted by SLC2A1inhibitor BAY-876. In mechanism, BMP4 activated SMAD5 to regulate the promoter of SLC2A1to enhance its expression. The in vivo xenograft experiments revealed that BMP4 promoted glycogen accumulation and tumor growth, which were effectively diminished by BAY-876. CONCLUSION: These results demonstrate that BMP4 upregulates glycogen synthesis through the SMAD/SLC2A1 (GLUT1) signaling axis in HCC cells, which may be exploited as novel therapeutic targets for HCC treatment.

Supramolecular photosensitizers using extended macrocyclic hosts for photodynamic therapy with distinct cellular delivery.

The photosensitizers (PSs) for photodynamic therapy (PDT) mostly possess conjugated skeletons that are over-sized and poorly water-soluble to be encapsulated by conventional macrocyclic receptors. Herein, we report that two fluorescent hydrophilic cyclophanes, AnBox·4Cl and ExAnBox·4Cl, can effectively bind hypocrellin B (HB), a pharmaceutically active natural PS for PDT, with binding constants of the 107 level in aqueous solutions. The two macrocycles feature extended electron-deficient cavities and can be facilely synthesized through photo-induced ring expansions. The corresponding supramolecular PSs (HB⊂AnBox4+ and HB⊂ExAnBox4+) exhibit desirable stability, biocompatibility, and cellular delivery, as well as excellent PDT efficiency against cancer cells. In addition, living cell imaging results indicate that HB⊂AnBox4+ and HB⊂ExAnBox4+ have different delivery effects at the cellular level.

Grandchild care and life satisfaction of older adults: Empirical evidence from China.

Background: In China, grandchild care plays an important social role later in life. The effects of grandchild care on physical health and depression in older adults have been illustrated. However, there is a gap in research on grandchild care and life satisfaction of older adults specifically based on the Chinese experience. Method: Based on 7,079 individuals' data from 2018 China Longitudinal Aging Social Survey (CLASS), this study explored the impact of grandchild care on older adults' life satisfaction by using Ordinary Least Squares (OLS), Propensity Score Matching (PSM), and instrumental variables (IV) models. Results: The empirical results indicated that (1) life satisfaction was significantly higher for older adults who undertook grandchild care compared to those who did not; (2) non-coresiding grandparents showed higher life satisfaction than those non-carers, and this effect was not found in custodial grandparents or three-generation household grandparents; (3) higher life satisfaction of grandchild caregivers was achieved through reduced loneliness, enhanced self-efficacy, and increased emotional support from children, with the latter being the greatest contribution; and (4) the improving effect of grandchild care on life satisfaction was found mainly in the group of older adults who were male and in rural households. Conclusion: There was a significant difference in life satisfaction between older Chinese adults who provided grandchild care and those who did not. Efforts in terms of old age policy protection and family relationships should be made to enhance the subjective well-being of older adults.

Elevated random glucose levels at admission are associated with all-cause mortality and cardiogenic shock during hospitalisation in patients with acute myocardial infarction and without diabetes: A retrospective cohort study.

BACKGROUND: Elevated glucose levels at admission are associated with a worse prognosis in patients with acute myocardial infarction (AMI); additionally, such elevation has a higher prognostic value for patients without diabetes. METHODS: We retrospectively recruited 2412 AMI patients without diabetes from 1 August 2011 to 10 January 2022. The primary outcome was all-cause mortality during hospitalisation, and the secondary outcomes were cardiogenic shock, ventricular tachycardia, ventricular fibrillation, atrioventricular block and new stroke. RESULTS: The mean age of participants was 65 years and 78.6% were male. Of the 2412 patients, all-cause mortality occurred in 236 patients (9.8%) during hospitalisation. In multivariate-adjusted models that corrected for variable weights, the risk of all-cause mortality increased with an increase in random glucose levels at admission; specifically, the risk of all-cause mortality increased per 1 mg/dL (odds ratio [OR] 1.006, 95% confidence interval [CI]: 1.004-1.008), per 9 mg/dL (OR: 1.06, 95% CI: 1.04-1.08), and per 18 mg/dL (OR: 1.12, 95% CI: 1.07-1.16) increases in admission glucose levels. When admission glucose levels were expressed as a categorical variable, increased levels of glucose (relative to the reference glucose value <140 mg/dL) led to an increased risk of all-cause mortality; specifically, the OR of all-cause mortality for 140-200 mg/dL glucose was 1.55 (95% CI: 1.09-2.17) and the OR for glucose >200 mg/dL was 3.08 (95% CI: 2.00-4.62) (P for trend <0.001). The risk of cardiogenic shock also increased with glucose levels with an OR of 1.68 (95% CI: 1.21-2.31) for 140-200 mg/dL glucose and an OR of 3.72 (95% CI: 2.50-5.46) for >200 mg/dL, compared with that of glucose <140 mg/dL. In multivariate-adjusted spline regression models, an increased risk of all-cause mortality was observed in patients with glucose ≥122 mg/dL (OR: 1.81, 95% CI: 1.38-2.38, p < 0.001) compared with the reference cohort. Furthermore, patients with glucose ≥111 mg/dL (OR: 2.36, 95% CI: 1.80-3.12) had a higher risk of cardiogenic shock than patients with glucose <111 mg/dL. CONCLUSIONS: Patients with AMI and without diabetes who had elevated random glucose levels at admission had a higher risk of all-cause mortality and cardiogenic shock during hospitalisation. In particular, patients with glucose ≥122 mg/dL had an increased risk of all-cause mortality, and those with glucose ≥111 mg/dL had an increased risk of cardiogenic shock.

Rational Molecular Design Strategy for High-Efficiency Ultrapure Blue TADF Emitters: Symmetrical and Rigid Sulfur-Bridged Boron-Based Acceptors.

Developing highly efficient blue thermally activated delayed fluorescence (TADF) emitters with a narrowband emission is still a challenge. Here, novel ultrapure blue TADF emitters of TSBA-Cz and TSBA-PhCz were designed and synthesized for organic light-emitting diodes (OLEDs). Photophysical and time-dependent density functional theory calculation results simultaneously show the similar intramolecular charge-transfer character of MR-type TADF emitters. Benefiting from the symmetrical and rigid molecular configuration, compounds TSBA-Cz and TSBA-PhCz emit a pure blue emission peak at 463 and 470 nm, a narrow full width at half-maximum (FWHM) of 30 and 36 nm, and a small singlet-triplet energy gap (ΔEST) of 0.21 and 0.18 eV, respectively, facilitating their excellent TADF behavior in doped films. Furthermore, highly efficient TADF-OLED devices using the TSBA-Cz and TSBA-PhCz with external quantum efficiencies of 23.4 and 21.3% emit ultrapure blue electroluminescence (EL) at 464 and 472 nm with a narrow FWHM of about 35 nm and CIE color coordinates of (0.14, 0.11) and (0.12, 0.18). This work provides novel TADF emitters for blue OLEDs with narrowband EL.

Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies.

Glycogen storage disease type I (GSDI) is an inherited metabolic disorder characterized by a deficiency of enzymes or proteins involved in glycogenolysis and gluconeogenesis, resulting in excessive intracellular glycogen accumulation. While GSDI is classified into four different subtypes based on molecular genetic variants, GSDIa accounts for approximately 80%. GSDIa and GSDIb are autosomal recessive disorders caused by deficiencies in glucose-6-phosphatase (G6Pase-α) and glucose-6-phosphate-transporter (G6PT), respectively. For the past 50 years, the care of patients with GSDI has been improved following elaborate dietary managements. GSDI patients currently receive dietary therapies that enable patients to improve hypoglycemia and alleviate early symptomatic signs of the disease. However, dietary therapies have many limitations with a risk of calcium, vitamin D, and iron deficiency and cannot prevent long-term complications, such as progressive liver and renal failure. With the deepening understanding of the pathogenesis of GSDI and the development of gene therapy technology, there is great progress in the treatment of GSDI. Here, we review the underlying molecular genetics and the current clinical management strategies of GSDI patients with an emphasis on promising experimental gene therapies.

Identification and characterization of CsSRP43, a major gene controlling leaf yellowing in cucumber.

Mutants are crucial to extending our understanding of genes and their functions in higher plants. In this study a spontaneous cucumber mutant, yf, showed yellow color leaves, had significant decreases in related physiological indexes of photosynthesis characteristics, and had more abnormal chloroplasts and thylakoids. Inheritance analysis indicated that the yellow color of the leaf was controlled by a recessive nuclear locus, yf. A candidate gene, CsSRP43, encoding a chloroplast signal recognition particle 43 protein, was identified through map-based cloning and whole-genome sequence analysis. Alignment of the CsSRP43 gene homologs between both parental lines revealed a 7-kb deletion mutation including the promoter region and the coding sequence in the yf mutant. In order to determine if the CsSRP43 gene was involved in the formation of leaf color, the CRISPR/Cas9-mediate system was used to modify CsSRP43 in the 9930 background; two independent transgenic lines, srp43-1 and srp43-2, were generated, and they showed yellow leaves with abnormal chloroplasts and thylakoids. Transcriptomic analysis revealed that differentially expressed genes associated with the photosynthesis-related pathway were highly enriched between srp43-1 and wild type, most of which were significantly downregulated in line srp43-1. Furthermore, yeast two-hybrid and biomolecular fluorescence complementation assays were used to confirm that CsSRP43 directly interacted with LHCP and cpSRP54 proteins. A model was established to explain the molecular mechanisms by which CsSRP43 participates in the leaf color and photosynthesis pathway, and it provides a valuable basis for understanding the molecular and genetic mechanisms of leaf color in cucumber.

Atomic Ramsey interferometry with S- and D-band in a triangular optical lattice.

Ramsey interferometers have wide applications in science and engineering. Compared with the traditional interferometer based on internal states, the interferometer with external quantum states has advantages in some applications for quantum simulation and precision measurement. Here, we develop a Ramsey interferometry with Bloch states in S- and D-band of a triangular optical lattice for the first time. The key to realizing this interferometer in two-dimensionally coupled lattice is that we use the shortcut method to construct π/2 pulse. We observe clear Ramsey fringes and analyze the decoherence mechanism of fringes. Further, we design an echo π pulse between S- and D-band, which significantly improves the coherence time. This Ramsey interferometer in the dimensionally coupled lattice has potential applications in the quantum simulations of topological physics, frustrated effects, and motional qubits manipulation.

A mechanically robust and stable estradiol-loaded PHEMA-based hydrogel barrier for intrauterine adhesion treatment.

Estrogen combined with physical barrier therapy may be a prospective method to repair a damaged endometrium and prevent postsurgical re-adhesion in the treatment of intrauterine adhesions (IUAs), but there lacks a suitable scaffold with good biocompatibility, appropriate mechanical properties, and drug-releasing kinetics. Herein, a mechanically robust and stable barrier based on the poly(hydroxyethyl methacrylate) (PHEMA) hydrogel combined with estradiol-loaded mesoporous silica is designed. The network is formed by covalent bonds and noncovalent coordination bonds, which endow the hydrogel with superior mechanical properties to most reported PHEMA-based hydrogels. Meanwhile, the covalent bonds impart excellent stability to the hydrogel, which maintains its structure and mechanical properties in a simulated uterine fluid for 30 days. The excellent mechanical properties and stability are comparable to those of a typical barrier material intrauterine device (IUD), enabling the hydrogel to be retained in the uterus and removed intact like an IUD. In vitro and in vivo experiments show that the hydrogel possesses good biocompatibility similar to pure PHEMA hydrogels. In addition, the hydrogel releases estradiol continuously and stably, and exhibits a good therapeutic effect in promoting the proliferation of endometrial cells and inhibiting the progression of fibrosis. Therefore, the combinational advantages make the present hydrogel very promising in IUA treatment.

Carboxymethyl chitosan prolongs adenovirus-mediated expression of IL-10 and ameliorates hepatic fibrosis in a mouse model.

Effective and safe liver-directed gene therapy has great promise in treating a broad range of liver diseases. While adenoviral (Ad) vectors have been widely used for efficacious in vivo gene delivery, their translational utilities are severely limited due to the short duration of transgene expression and solicitation of host immune response. Used as a promising polymeric vehicle for drug release and nucleic acid delivery, carboxymethyl chitosan (CMC) is biocompatible, biodegradable, anti-microbial, inexpensive, and easy accessible. Here, by exploiting its biocompatibility, controlled release capability and anti-inflammatory activity, we investigated whether CMC can overcome the shortcomings of Ad-mediated gene delivery, hence improving the prospect of Ad applications in gene therapy. We demonstrated that in the presence of optimal concentrations of CMC, Ad-mediated transgene expression lasted up to 50 days after subcutaneous injection, and at least 7 days after intrahepatic injection. Histologic evaluation and immunohistochemical analysis revealed that CMC effectively alleviated Ad-induced host immune response. In our proof-of-principle experiment using the CCl4-induced experimental mouse model of chronic liver damage, we demonstrated that repeated intrahepatic administrations of Ad-IL10 mixed with CMC effectively mitigated the development of hepatic fibrosis. Collectively, these results indicate that CMC can improve the prospect of Ad-mediated gene therapy by diminishing the host immune response while allowing readministration and sustained transgene expression.